Prioritizing Functional Capacity as a Principal End Point for Therapies Oriented to Older Adults With Cardiovascular Disease: A Scientific Statement for Healthcare Professionals From the American Heart Association

Probably not a substantial claim: may not pass S4 (based).

Comorbidity, inflammation, mitochondrial metabolism, cognition, balance, and sleep are among factors that affect cardiorespiratory function and become entwined with cardiovascular health in old age.

“Comorbidity, inflammation, mitochondrial metabolism, cognition, balance, and sleep are among the constellation of factors that bear on cardiorespiratory function and that become intricately entwined with cardiovascular health in old age.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Since 1900, average longevity in the United States has increased by more than 30 years.

“Since 1900, the average longevity in the United States has increased >30 years.1”

• cites [1] Centers for Disease Control and Prevention. Table 22: life expectancy at birth, at 65 years of age, and at 75 years of age, by race and sex: United States, selected years 1900–2007. http://www.cdc.gov/nchs/data/hus/2010/022.pdf. Accessed May 15, 2016.Not checked yet

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May combine two claims.

Functional capacity is a key metric in older adults, both as a measure of aggregate health and as a goal of care.

“Functional capacity is a key metric in this population, both for the perspective it provides on aggregate health and as a vital goal of care.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Between 2010 and 2050, the population aged 65 and older in the United States is expected to more than double to about 88.5 million, about 25% of the anticipated population.

“Between 2010 and 2050, the population ≥65 years of age is expected to more than double to reach ≈88.5 million, ≈25% of the anticipated population.1”

• cites [1] Centers for Disease Control and Prevention. Table 22: life expectancy at birth, at 65 years of age, and at 75 years of age, by race and sex: United States, selected years 1900–2007. http://www.cdc.gov/nchs/data/hus/2010/022.pdf. Accessed May 15, 2016.Not checked yet

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Cardiorespiratory function has long been used by cardiologists as a measure of function depending primarily on cardiac physiology, but multiple other factors also contribute, with increasing bearing as age advances.

“Whereas cardiorespiratory function has long been applied by cardiologists as a measure of function that depended primarily on cardiac physiology, multiple other factors also contribute, usually with increasing bearing as age advances.”

May combine two claims.

CRF is a leading measure of health; declining functional capacity typically surpasses all other cardiovascular risks; and the hazard of declining CRF tends to worsen with aging.

“CRF is a leading measure of health; declining functional capacity typically surpasses all other cardiovascular risks; and the hazard of declining CRF tends to worsen with aging.”

May combine two claims.

In healthy adults, peak VO2 declines on average by 8% to 10% per decade, with accelerating declines as age advances.

“In healthy adults, peak V˙o2 declines on average by 8% to 10% per decade, wit.h accelerating declines as age advances.10”

• cites [10] Fleg JL, Morrell CH, Bos AG, Brant LJ, Talbot LA, Wright JG, Lakatta EG. Accelerated longitudinal decline of aerobic capacity in healthy older adults. Circulation. 2005; 112: 674– 682. doi: 10.1161/CIRCULATIONAHA.105.545459. 16043637 sourceNot checked yet

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Muscle mass constitutes 30% of body weight in younger adults and decreases to about 15% of body weight by 75 years of age.

“Whereas muscle mass constitutes 30% of body weight in younger adults, it decreases to ≈15% of body weight by 75 years of age.17”

• cites [17] Manologas S. Aging and the musculoskeletal system In: Beers MH, and Berkow R, eds. The Merck Manual of Geriatrics, Third Edition. Whitehouse Station, NJ: Merck Research Laboratories; 2000: 467– 472.Not checked yet

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Many individuals then choose to avoid tasks that have become relatively more stressful, with the result that physical activity and CRF become further reduced.

“Many individuals then choose to avoid tasks that have become relatively more stressful, with the result that physical activity and CRF become further reduced.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Peak VO2 is an assessment of maximal aerobic performance that implies activity has intensified to a point of maximal volition, and it is usually assessed as part of a symptom-limited or maximum exercise test.

“Peak V˙o2 is an assessment of maximal aerobic performance that implies that activity has intensified to a point of maximal volition; hence, peak V˙o2 is usually assessed as part of a symptom-limited or maximum exercise test.7”

• cites [7] Arena R, Myers J, Williams MA, Gulati M, Kligfield P, Balady GJ, Collins E, Fletcher G. Assessment of functional capacity in clinical and research settings: a scientific statement from the American Heart Association Committee on Exercise, Rehabilitation, and Prevention of the Council on Clinical Cardiology and the Council on Cardiovascular Nursing. Circulation. 2007; 116: 329– 343. doi: 10.1161/CIRCULATIONAHA.106.184461. 17576872 sourceNot checked yet

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Balance and flexibility are required for many daily activities and decline with age, especially in the context of changing muscle mass and function, neurogenic factors, bone loss, and degenerative changes in connective tissue.

“Balance and flexibility are also required for many daily activities and decline with age, especially in the context of changing muscle mass and function, neurogenic factors, bone loss, and degenerative changes in connective tissue.18”

• cites [18] Forman DE, Fleg JL. Exercise in older adults In: Ehrman JK, Gordon PM, Visich PS, Keteyian SJ, eds. Clinical Exercise Physiology Champaign, IL: Human Kinetics; 2013; 589– 604.Not checked yet

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Adults who survive into old age are predictably more vulnerable to becoming sedentary and to a cycle in which multimorbidities and hospitalizations compound functional decrements, exacerbating risks of disability, dependency, and frailty.

“Adults who survive into old age are predictably more vulnerable to becoming sedentary and to a cycle wherein multimorbidities and hospitalizations compound functional decrements, which exacerbate risks of disability, dependency, and frailty.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Sarcopenia, the age-associated loss of skeletal muscle mass, involves both loss of muscle fibers and reduced fiber size.

“Age-associated loss of skeletal muscle mass, called sarcopenia, involves both loss of muscle fibers and reduced fiber size.16”

• cites [16] Deschenes MR. Effects of aging on muscle fibre type and size. Sports Med 2004; 34: 809– 824. 15462613 sourceNot checked yet

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Many older patients regard preserved function, independence, and related self-efficacy as their primary goals of care, and for many, conserved functional capabilities become more important than traditional disease-specific therapeutic end points.

“many older patients regard preserved function, independence, and related self-efficacy as their primary goals of care; that is, for many patients, conserved functional capabilities become more important than traditional disease-specific therapeutic end points.5”

• cites [5] Fried TR, McGraw S, Agostini JV, Tinetti ME. Views of older persons with multiple morbidities on competing outcomes and clinical decision-making. J Am Geriatr Soc 2008; 56: 1839– 1844. doi: 10.1111/j.1532-5415.2008.01923.x. 18771453 PMC2596278 sourceNot checked yet

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May combine two claims.

The primary metric of functional capacity is cardiorespiratory fitness (CRF), usually assessed as peak oxygen uptake (VO2).

“The primary metric of functional capacity is cardiorespiratory fitness (CRF), usually assessed as peak oxygen uptake (V˙o2).6”

• cites [6] Lavie CJ, Arena R, Swift DL, Johannsen NM, Sui X, Lee DC, Earnest CP, Church TS, O’Keefe JH, Milani RV, Blair SN. Exercise and the cardiovascular system: clinical science and cardiovascular outcomes. Circ Res 2015; 117: 207– 219. doi: 10.1161/CIRCRESAHA.117.305205. 26139859 PMC4493772 sourceNot checked yet

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Cardiologists have tended to regard peak VO2 as a particularly valuable index for heart function because VO2 can be applied as a proxy for cardiac output, and this is most commonly used as part of heart failure management.

“Cardiologists have tended to regard peak V˙o2 as a particularly valuable index for heart function because V˙o2 can be applied as a proxy for cardiac output,8 and this is most commonly used as part of heart failure (HF) management.”

• cites [8] Balady GJ, Arena R, Sietsema K, Myers J, Coke L, Fletcher GF, Forman D, Franklin B, Guazzi M, Gulati M, Keteyian SJ, Lavie CJ, Macko R, Mancini D, Milani RV; on behalf of the American Heart Association Exercise, Cardiac Rehabilitation, and Prevention Committee of the Council on Clinical Cardiology; Council on Epidemiology and Prevention; Council on Peripheral Vascular Disease; Interdisciplinary Council on Quality of Care and Outcomes Research. Clinician’s guide to cardiopulmonary exercise testing in adults: a scientific statement from the American Heart Association. Circulation. 2010; 122: 191 sourceNot checked yet

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Cardiovascular and pulmonary physiological components are key determinants of VO2 and usually predominate in younger adults, but vascular, skeletal muscle, autonomic, hematologic, and other mechanisms also contribute and often factor more significantly in older age.

“Cardiovascular and pulmonary physiological components are key determinants of V˙o2 and usually predominate in younger adults, but vascular, skeletal muscle, autonomic, hematologic, and other physiological mechanisms are also contributory and often factor relatively more significantly in older age.”

May combine two claims.

Cellular mitochondrial quality control mechanisms such as autophagy and the ubiquitin-protease system become impaired with aging, resulting in accumulation of dysfunctional mitochondria, which further contribute to myocardial functional impairment and CVD.

“In addition, cellular mitochondrial quality control mechanisms such as autophagy and ubiquitin-protease system, which removes damaged mitochondria or protein to maintain a functional mitochondrial network, become impaired with aging, resulting in an accumulation of dysfunctional mitochondria, which further contribute to myocardial functional impairment and CVD.31”

• cites [31] Wohlgemuth SE, Calvani R, Marzetti E. The interplay between autophagy and mitochondrial dysfunction in oxidative stress-induced cardiac aging and pathology. J Mol Cell Cardiol 2014; 71: 62– 70. doi: 10.1016/j.yjmcc.2014.03.007. 24650874 sourceNot checked yet

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These processes contribute to susceptibility to disease and declines in functional status that extend beyond any one disease and can even occur in health.

“Together, these processes contribute to susceptibility to disease and declines in functional status that extend beyond any one disease and that can even occur in health.26”

• cites [26] Olivieri F, Recchioni R, Marcheselli F, Abbatecola AM, Santini G, Borghetti G, Antonicelli R, Procopio AD. Cellular senescence in cardiovascular diseases: potential age-related mechanisms and implications for treatment. Curr Pharm Des 2013; 19: 1710– 1719. 23061728Not checked yet

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CPET indexes reveal physiological components in addition to the cardiac physiology underlying CRF, and the overall implication of functional assessment extends beyond delineation of underlying physiologies.

“However, not only do CPET indexes reveal physiological components in addition to the cardiac physiology that underlies CRF (eg, CPET indexes indicative of pulmonary, skeletal muscle, and autonomic impact), but the overall implication of functional assessment extends beyond such mere delineation of underlying physiologies.”

May combine two claims.

Diminished sleep quality (shorter and more fragmented) is common in older cardiovascular patients and often adds to fatigue and exercise intolerance.

“Diminished sleep quality (shorter and more fragmented) is also common in older cardiovascular patients and often adds to fatigue and exercise intolerance.25”

• cites [25] Crane PB. Fatigue and physical activity in older women after myocardial infarction. Heart Lung 2005; 34: 30– 38. doi: 10.1016/j.hrtlng.2004.08.007. 15647732 sourceNot checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

Oxygen use is ideally measured by cardiopulmonary exercise testing (CPET).

“Oxygen use is ideally measured by cardiopulmonary exercise testing (CPET).”

Probably not a substantial claim: may not pass S3 (load-bearing).

Peak VO2 corresponds to the product of heart rate, stroke volume, and systemic arteriovenous oxygen difference at maximal effort.

“Peak V˙o2 corresponds to the product of heart rate (HR), stroke volume, and systemic arteriovenous oxygen difference (ΔAV˙o2) at maximal effort.”

May combine two claims.

Depression compounds impediments with intensified cardiovascular, immune, and hormonal pathophysiologies, as well as poorer adherence to multiple healthy lifestyle activities and medications.

“depression compounds impediments with intensified cardiovascular, immune, and hormonal pathophysiologies,21,22 as well as poorer adherence to multiple healthy lifestyle activities (eg, smoking cessation, exercise, diet) and medications.23,24”

• cites [21] Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, Das SR, de Ferranti S, Despres JP, Fullerton HJ, Howard VJ, Huffman MD, Isasi CR, Jimenez MC, Judd SE, Kissela BM, Lichtman JH, Lisabeth LD, Liu S, Mackey RH, Magid DJ, McGuire DK, Mohler ER 3rd, Moy CS, Muntner P, Mussolino ME, Nasir K, Neumar RW, Nichol G, Palaniappan L, Pandey DK, Reeves MJ, Rodriguez CJ, Rosamond W, Sorlie PD, Stein J, Towfighi A, Turan TN, Virani SS, Woo D, Yeh RW, Turner MB; on behalf of the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statis sourceNot checked yet

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• cites [22] Lichtman JH, Bigger JT Jr, Blumenthal JA, Frasure-Smith N, Kaufmann PG, Lespérance F, Mark DB, Sheps DS, Taylor CB, Froelicher ES. Depression and coronary heart disease: recommendations for screening, referral, and treatment: a science advisory from the American Heart Association Prevention Committee of the Council on Cardiovascular Nursing, Council on Clinical Cardiology, Council on Epidemiology and Prevention, and Interdisciplinary Council on Quality of Care and Outcomes Research. Circulation. 2008; 118: 1768– 1775. doi: 10.1161/CIRCULATIONAHA.108.190769. 18824640 sourceNot checked yet

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• cites [23] Sin NL, Kumar AD, Gehi AK, Whooley MA. Direction of association between depressive symptoms and lifestyle behaviors in patients with coronary heart disease: the Heart and Soul Study. Ann Behav Med 2016; 50: 523– 532. doi: 10.1007/s12160-016-9777-9. 26817654 PMC4935549 sourceNot checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Metabolic equivalents (METs) achieved are a surrogate indicator of exercise performance calculated from workload and often used as an alternative to CPET when ventilatory expired gas analysis is not available.

“Metabolic equivalents (METs) achieved are a surrogate indicator of exercise performance that are calculated from workload (ie, treadmill speed/grade or Watts) and often used as an alternative to CPET when ventilatory expired gas analysis is not available.”

May combine two claims.

Strength and neuromuscular function contribute to CRF, with a proportionally greater role in determining peak VO2 as strength and coordination decline.

“In addition to cardiovascular physiological components,4 strength and neuromuscular function contribute to CRF with a proportionally greater role in determining peak V˙o2 as strength and coordination decline.14”

• cites [14] Bean JF, Kiely DK, LaRose S, Leveille SG. Which impairments are most associated with high mobility performance in older adults? Implications for a rehabilitation prescription. Arch Phys Med Rehabil 2008; 89: 2278– 2284. doi: 10.1016/j.apmr.2008.04.029. 19061739 sourceNot checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The very old subgroup (≥85 years) is growing most rapidly and is expected to triple over 2010-2050 to about 4.5% of the population.

“Within this total, the very old subgroup (ie, those ≥85 years of age) is growing the most rapidly and is expected to triple over the same period to ≈4.5% of the population.2”

• cites [2] Ortman JM, Velkoff VA, Hogan H. An aging nation: the older population in the United States. 2014 https://www.census.gov/prod/2014pubs/p25-1140.pdf. Accessed January 14, 2017.Not checked yet

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Pinsky et al. reported that angina pectoris was more predictive of disability than extent of underlying CHD, suggesting that a patient's sense of discomfort and apprehension was likely more impactful than the underlying physiology.

“Pinsky et al47 reported that angina pectoris was more predictive of disability than extent of underlying CHD, suggesting that a patient’s sense of discomfort and apprehension was likely more impactful than the underlying physiology.”

• cites [47] Pinsky JL, Jette AM, Branch LG, Kannel WB, Feinleib M. The Framingham Disability Study: relationship of various coronary heart disease manifestations to disability in older persons living in the community. Am J Public Health 1990; 80: 1363– 1367. 2240306 PMC1404890 sourceNot checked yet

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The inflammatory milieu further contributes to aging-associated functional decline via reactive oxidative species-mediated exacerbation of telomere dysfunction and accelerated muscle catabolism, promoting cell senescence and subsequent disease, frailty, and mortality.

“This inflammatory milieu further contributes to aging-associated functional decline via reactive oxidative species–mediated exacerbation of telomere dysfunction34 and accelerated muscle catabolism, promoting cell senescence and subsequent disease, frailty, and mortality.33,35,36”

• cites [33] Brüünsgaard H, Pedersen BK. Age-related inflammatory cytokines and disease. Immunol Allergy Clin North Am 2003; 23: 15– 39. 12645876 sourceNot checked yet

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• cites [35] Kalogeropoulos A, Georgiopoulou V, Psaty BM, Rodondi N, Smith AL, Harrison DG, Liu Y, Hoffmann U, Bauer DC, Newman AB, Kritchevsky SB, Harris TB, Butler J; Health ABC Study Investigators. Inflammatory markers and incident heart failure risk in older adults: the Health ABC (Health, Aging, and Body Composition) study. J Am Coll Cardiol 2010; 55: 2129– 2137. doi: 10.1016/j.jacc.2009.12.045. 20447537 PMC3267799 sourceNot checked yet

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• cites [36] Liu CK, Lyass A, Larson MG, Massaro JM, Wang N, D’Agostino RB Sr, Benjamin EJ, Murabito JM. Biomarkers of oxidative stress are associated with frailty: the Framingham Offspring Study. Age (Dordr) 2016; 38: 1. doi: 10.1007/s11357-015-9864-z. 26695510 PMC5005887 sourceNot checked yet

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Probably not a substantial claim: may not pass S2 (checkable). May combine two claims.

Functional capacity is more than a tally of causal physiological mechanisms; the patient experience is more personal and distinctive.

“Whereas cardiac output and numerous other factors are now recognized to affect CRF, functional capacity is still more than a tally of causal physiological mechanisms. The patient experience is more personal and distinctive.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Higher self-efficacy has led to greater self-esteem.

“Higher self-efficacy has also led to greater self-esteem.121”

• cites [121] Elavsky S, McAuley E, Motl RW, Konopack JF, Marquez DX, Hu L, Jerome GJ, Diener E. Physical activity enhances long-term quality of life in older adults: efficacy, esteem, and affective influences. Ann Behav Med 2005; 30: 138– 145. doi: 10.1207/s15324796abm3002_6. 16173910 sourceNot checked yet

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Aerobic training benefits include subcellular shifts in gene expression, boosted cellular metabolism, greater organ efficiency, and enhanced systemic biological and physiological integration.

“Aerobic benefits include subcellular shifts in gene expression (triggered in part by reduced inflammation), boosted cellular metabolism (improved bioenergetics and insulin sensitivity), greater organ efficiency (including increased cardiac, vascular, pulmonary, muscular, neurologic, and cognitive performance), and enhanced systemic biological and physiological integration.6”

• cites [6] Lavie CJ, Arena R, Swift DL, Johannsen NM, Sui X, Lee DC, Earnest CP, Church TS, O’Keefe JH, Milani RV, Blair SN. Exercise and the cardiovascular system: clinical science and cardiovascular outcomes. Circ Res 2015; 117: 207– 219. doi: 10.1161/CIRCRESAHA.117.305205. 26139859 PMC4493772 sourceNot checked yet

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May combine two claims.

Numerous subsequent studies have demonstrated up to 25% increases in peak VO2 in previously sedentary healthy adults through the ninth decade, similar to improvements in younger adults.

“numerous subsequent studies have demonstrated up to 25% increases in peak V˙o2 in previously sedentary healthy adults through the ninth decade, similar to improvements found in younger adults.143–145”

• cites [143] Hagberg JM, Graves JE, Limacher M, Woods DR, Leggett SH, Cononie C, Gruber JJ, Pollock ML. Cardiovascular responses of 70-to 79-yr-old men and women to exercise training. J Appl Physiol (1985) 1989; 66: 2589– 2594. 2745320 sourceNot checked yet

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• cites [144] Huang G, Gibson CA, Tran ZV, Osness WH. Controlled endurance exercise training and VO2max changes in older adults: a meta-analysis. Prev Cardiol 2005; 8: 217– 225. 16230876 sourceNot checked yet

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• cites [145] Beere PA, Russell SD, Morey MC, Kitzman DW, Higginbotham MB. Aerobic exercise training can reverse age-related peripheral circulatory changes in healthy older men. Circulation. 1999; 100: 1085– 1094. 10477534 sourceNot checked yet

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Probably not a substantial claim: may not pass S2 (checkable). May combine two claims.

The challenge for research is not only to study therapies based on mechanistic insights pertaining to CVD but also to assess efficacy of therapies from patient-centered perspectives; the number of events may be less important than the patient's personal experience.

“The challenge for research is not only to study therapies based on mechanistic insights pertaining to CVD but also to assess efficacy of therapies from patient-centered perspectives; that is, the number of events may be less important than the patient’s personal experience.”

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

Age-related nutritional decline is common amid age-related changes in taste, dentition, digestion, absorption, and cognition, as well as limitations in access.

“Age-related nutritional decline is common amid age-related changes in taste, dentition, digestion, absorption, and cognition, as well as limitations in access (logistics, cost, and the challenge of food preparation).”

May combine two claims.

Many different measures of frailty exist, but physical frailty is conceptually distinctive from the frailty index and relates more directly to functional attributes.

“Although many different measures of frailty exist, physical frailty is conceptually distinctive from the frailty index39,41,42 and relates more directly to functional attributes.41,42”

• cites [39] Forman DE, Alexander KP. Frailty: a vital sign for older adults with cardiovascular disease. Can J Cardiol 2016; 32: 1082– 1087. doi: 10.1016/j.cjca.2016.05.015. 27476987 sourceNot checked yet

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• cites [41] Afilalo J, Alexander KP, Mack MJ, Maurer MS, Green P, Allen LA, Popma JJ, Ferrucci L, Forman DE. Frailty assessment in the cardiovascular care of older adults. J Am Coll Cardiol 2014; 63: 747– 762. doi: 10.1016/j.jacc.2013.09.070. 24291279 PMC4571179 sourceNot checked yet

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• cites [42] Abellan van Kan G, Rolland Y, Bergman H, Morley JE, Kritchevsky SB, Vellas B. The I.A.N.A Task Force on frailty assessment of older people in clinical practice. J Nutr Health Aging 2008; 12: 29– 37. 18165842 sourceNot checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

The impact of high ambient inflammation is exacerbated by depletion of vital nutrient and energy stores with worsening fatigue and cellular harm.

“The impact of high ambient inflammation is exacerbated by the depletion of vital nutrient and energy stores with worsening fatigue and cellular harm.”

May combine two claims.

Gait speed is widely used as a single frailty measure and has prognostic importance across diverse populations and performance levels.

“Gait speed has been widely used as a single measure of frailty and is supported by a robust body of literature demonstrating its prognostic importance across a wide range of patient populations and performance levels.85”

• cites [85] Abellan van Kan G, Rolland Y, Andrieu S, Bauer J, Beauchet O, Bonnefoy M, Cesari M, Donini LM, Gillette Guyonnet S, Inzitari M, Nourhashemi F, Onder G, Ritz P, Salva A, Visser M, Vellas B. Gait speed at usual pace as a predictor of adverse outcomes in community-dwelling older people: an International Academy on Nutrition and Aging (IANA) Task Force. J Nutr Health Aging 2009; 13: 881– 889. 19924348 sourceNot checked yet

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Because the peak VO2 of most healthy female octogenarians is often below 18 mL·kg−1·min−1, many are close to a threshold at which functional independence is no longer possible.

“Because the peak V˙o2 of most healthy female octogenarians is often below this level, many are close to a threshold at which functional independence is no longer possible.”

May combine two claims.

For older patients with CVD, exercise training benefits persist but are often surpassed by the value of exercise training to improve physical function and thereby enable ADLs and improved QOL.

“For older patients with CVD, these benefits persist but are often surpassed by the value of exercise training to improve capacity to improve physical function and to thereby better enable ADLs and improved QOL.”

May combine two claims.

The ASPREE trial is a novel approach to assessing the utility of platelet medication in senior adults; its primary end point is disability-free life, including dementia and persistent disability, rather than thromboembolic events, bleeding, and traditional metrics.

“The ASPREE trial (Aspirin in Reducing Events in the Elderly) stands out as a novel approach to assessing the utility of platelet medication in senior adults.48 Instead of measuring thromboembolic events, bleeding, and the traditional metrics that one might expect, the primary end point is disability-free life, including dementia and persistent disability.”

• cites [48] ASPREE Investigator Group. Study design of ASPirin in Reducing Events in the Elderly (ASPREE): a randomized, controlled trial. Contemp Clin Trials 2013; 36: 555– 564. 24113028 PMC3919683 sourceNot checked yet

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Considerable evidence exists for hospital-associated deconditioning and disability, including rapid loss of muscle mass and strength that contributes to slower gait speed and difficulty performing ADLs.

“Considerable evidence exists for hospital-associated deconditioning126,127 and disability, including rapid loss of muscle mass and strength128–132 that contributes to slower gait speed133–135 and difficulty performing ADLs.136–139”

• cites [126] Kortebein P Rehabilitation for hospital-associated deconditioning. Am J Phys Med Rehabil 2009; 88: 66– 77. doi: 10.1097/PHM.0b013e3181838f70. 18688198 sourceNot checked yet

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• cites [127] Kortebein P, Bopp MM, Granger CV, Sullivan DH. Outcomes of inpatient rehabilitation for older adults with debility. Am J Phys Med Rehabil 2008; 87: 118– 125. doi: 10.1097/PHM.0b013e3181588429. 17912135 sourceNot checked yet

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• cites [128] Berg HE, Eiken O, Miklavcic L, Mekjavic IB. Hip, thigh and calf muscle atrophy and bone loss after 5-week bedrest inactivity. Eur J Appl Physiol 2007; 99: 283– 289. doi: 10.1007/s00421006-0346-y. 17186305 sourceNot checked yet

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• cites [129] Bloomfield SA. Changes in musculoskeletal structure and function with prolonged bed rest. Med Sci Sports Exerc 1997; 29: 197– 206. 9044223 sourceNot checked yet

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• cites [130] Brown CJ, Redden DT, Flood KL, Allman RM. The underrecognized epidemic of low mobility during hospitalization of older adults. J Am Geriatr Soc 2009; 57: 1660– 1665. doi: 10.1111/j.1532-5415.2009.02393.x. 19682121 sourceNot checked yet

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• cites [131] Convertino VA, Bloomfield SA, Greenleaf JE. An overview of the issues: physiological effects of bed rest and restricted physical activity. Med Sci Sports Exerc 1997; 29: 187– 190. 9044221 sourceNot checked yet

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• cites [132] Kortebein P, Ferrando A, Lombeida J, Wolfe R, Evans WJ. Effect of 10 days of bed rest on skeletal muscle in healthy older adults. JAMA 2007; 297: 1772– 1774. doi: 10.1001/jama.297.16.1772-b. 17456818 sourceNot checked yet

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• cites [133] Hruda KV, Hicks AL, McCartney N. Training for muscle power in older adults: effects on functional abilities. Can J Appl Physiol 2003; 28: 178– 189. 12825328 sourceNot checked yet

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• cites [134] Kalapotharakos VI, Diamantopoulos K, Tokmakidis SP. Effects of resistance training and detraining on muscle strength and functional performance of older adults aged 80 to 88 years. Aging Clin Exp Res 2010; 22: 134– 140. 20440099 sourceNot checked yet

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• cites [135] Rantanen T, Guralnik JM, Izmirlian G, Williamson JD, Simonsick EM, Ferrucci L, Fried LP. Association of muscle strength with maximum walking speed in disabled older women. Am J Phys Med Rehabil 1998; 77: 299– 305. 9715919 sourceNot checked yet

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May combine two claims.

Concomitant CVD, particularly HF, and noncardiovascular comorbidities tend to compound decrements in peak VO2, social risk, and the vicious circle whereby sedentariness progressively worsens disease.

“Concomitant CVD, particularly HF, and noncardiovascular comorbidities tend to compound decrements in peak V˙o2, social risk, and the insidious vicious circle whereby sedentariness progressively worsens disease.”

May combine two claims.

Frailty increases hospital length of stay and adverse outcomes in patients admitted for CVD, HF, CAD, and associated procedures and exacerbates risks of long-term disability thereafter.

“Frailty increases hospital length of stay and adverse outcomes in patients admitted for CVD, HF, CAD,41 and associated procedures (eg, cardiac valve replacement or arterial vascular surgery [aortic or lower limb arterial intervention])45,46 and exacerbates risks of long-term disability thereafter.”

• cites [41] Afilalo J, Alexander KP, Mack MJ, Maurer MS, Green P, Allen LA, Popma JJ, Ferrucci L, Forman DE. Frailty assessment in the cardiovascular care of older adults. J Am Coll Cardiol 2014; 63: 747– 762. doi: 10.1016/j.jacc.2013.09.070. 24291279 PMC4571179 sourceNot checked yet

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• cites [45] Partridge JS, Fuller M, Harari D, Taylor PR, Martin FC, Dhesi JK. Frailty and poor functional status are common in arterial vascular surgical patients and affect postoperative outcomes. Int J Surg 2015; 18: 57– 63. doi: 10.1016/j.ijsu.2015.04.037. 25907322 sourceNot checked yet

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• cites [46] Afilalo J, Eisenberg MJ, Morin JF, Bergman H, Monette J, Noiseux N, Perrault LP, Alexander KP, Langlois Y, Dendukuri N, Chamoun P, Kasparian G, Robichaud S, Gharacholou SM, Boivin JF. Gait speed as an incremental predictor of mortality and major morbidity in elderly patients undergoing cardiac surgery. J Am Coll Cardiol 2010; 56: 1668– 1676. doi: 10.1016/j.jacc.2010.06.039. 21050978 sourceNot checked yet

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May combine two claims.

Afilalo et al. observed that physical frailty may lead to CVD, just as CVD may lead to frailty.

“Afilalo et al44 observed that physical frailty may lead to CVD, just as CVD may lead to frailty.”

• cites [44] Afilalo J, Karunananthan S, Eisenberg MJ, Alexander KP, Bergman H. Role of frailty in patients with cardiovascular disease. Am J Cardiol 2009; 103: 1616– 1621. doi: 10.1016/j.amjcard.2009.01.375. 19463525 sourceNot checked yet

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May combine two claims.

Exercise training has a preponderance of data demonstrating decreased cardiovascular events and increased longevity.

“with a preponderance of data demonstrating decreased cardiovascular events and increased longevity.124”

• cites [124] Arena R, Williams M, Forman DE, Cahalin LP, Coke L, Myers J, Hamm L, Kris-Etherton P, Humphrey R, Bittner V, Lavie CJ; on behalf of the American Heart Association Exercise, Cardiac Rehabilitation and Prevention Committee of the Council on Clinical Cardiology, Council on Epidemiology and Prevention, and Council on Nutrition, Physical Activity and Metabolism. Increasing referral and participation rates to outpatient cardiac rehabilitation: the valuable role of healthcare professionals in the inpatient and home health settings: a science advisory from the American Heart Association. Circulation. sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

Health-related QOL at baseline may also influence self-efficacy.

“Conversely, health-related QOL at baseline may also influence self-efficacy.”

May combine two claims.

Physical function is an important indicator of prognostic risk and a key influence on daily life of older adults with CVD.

“Physical function is an important indicator of prognostic risk and a key influence on the daily life of older adults with CVD.110”

• cites [110] Lewis EF. Activities worth living for: call to action beyond prognosis. Circ Heart Fail 2015; 8: 231– 232. doi: 10.1161/CIRCHEARTFAILURE.115.002064. 25717058 sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Balance deficits are common in older cardiovascular patients, and along with functional strength and mobility training, may be important targets to maximize gains and reduce risk of injuries and falls.

“Balance deficits are also common in such patients, which, along with functional strength and mobility training, may be important targets to maximize gains and to reduce the risk of injuries and falls.”

May combine two claims.

Self-reported health status and depressive symptoms also improved modestly with aerobic exercise training.

“Self-reported health status198 and depressive symptoms199 also improved modestly with aerobic exercise training.”

• cites [198] Flynn KE, Piña IL, Whellan DJ, Lin L, Blumenthal JA, Ellis SJ, Fine LJ, Howlett JG, Keteyian SJ, Kitzman DW, Kraus WE, Miller NH, Schulman KA, Spertus JA, O’Connor CM, Weinfurt KP; HF-ACTION Investigators. Effects of exercise training on health status in patients with chronic heart failure: HF-ACTION randomized controlled trial [published correction appears in JAMA. 2009;302:2322]. JAMA 2009; 301: 1451– 1459. doi: 10.1001/jama.2009.457. 19351942 PMC2690699 sourceNot checked yet

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• cites [199] Blumenthal JA, Babyak MA, O’Connor C, Keteyian S, Landzberg J, Howlett J, Kraus W, Gottlieb S, Blackburn G, Swank A, Whellan DJ. Effects of exercise training on depressive symptoms in patients with chronic heart failure: the HF-ACTION randomized trial [published correction appears in JAMA. 2012;308:1742]. JAMA 2012; 308: 465– 474. doi: 10.1001/jama.2012.8720. 22851113 PMC3953459 sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Older patients with peripheral artery disease had improved exercise capacity, walking speed, and diminished claudication, along with underlying improvements in endothelial function, capillary density, and mitochondrial oxidative activity.

“Older patients with peripheral artery disease had improved exercise capacity, walking speed, and diminished claudication, along with underlying improvements in endothelial function,181 capillary density, and mitochondrial oxidative activity.”

• cites [181] Harwood AE, Cayton T, Sarvanandan R, Lane R, Chetter I. A review of the potential local mechanisms by which exercise improves functional outcomes in intermittent claudication. Ann Vasc Surg 2016; 30: 312– 320. doi: 10.1016/j.avsg.2015.05.043. 26362620 sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

Atherosclerosis is inherent to aging and has pervasive effects, including cardiovascular instability, underperfusion of skeletal muscle, cognitive changes, and neuromotor/cognitive impairments after stroke.

“Atherosclerosis is inherent to aging and has pervasive effects, including cardiovascular instability, underperfusion of skeletal muscle, cognitive changes, and neuromotor/cognitive impairments after stroke.”

• AssumptionRests on an assumption: Atherosclerosis is inherent to aging.

May combine two claims.

A consequence of the HF-mediated decline in peak VO2 is decreased physical functional performance and greater risk for poor outcomes.

“A consequence of the HF-mediated decline in peak V˙o2 is decreased physical functional performance and greater risk for poor outcomes.186,187,189–193”

• cites [186] Kitzman DW, Little WC, Brubaker PH, Anderson RT, Hundley WG, Marburger CT, Brosnihan B, Morgan TM, Stewart KP. Pathophysiological characterization of isolated diastolic heart failure in comparison to systolic heart failure. JAMA 2002; 288: 2144– 2150. 12413374 sourceNot checked yet

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• cites [187] Savage PA, Shaw AO, Miller MS, VanBuren P, LeWinter MM, Ades PA, Toth MJ. Effect of resistance training on physical disability in chronic heart failure. Med Sci Sports Exerc 2011; 43: 1379– 1386. doi: 10.1249/MSS.0b013e31820eeea1. 21233772 PMC3410739 sourceNot checked yet

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• cites [189] Haykowsky MJ, Brubaker PH, Morgan TM, Kritchevsky S, Eggebeen J, Kitzman DW. Impaired aerobic capacity and physical functional performance in older heart failure patients with preserved ejection fraction: role of lean body mass. J Gerontol A Biol Sci Med Sci 2013; 68: 968– 975. doi: 10.1093/gerona/glt011. 23525477 PMC3712362 sourceNot checked yet

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• cites [190] Keteyian SJ, Patel M, Kraus WE, Brawner CA, McConnell TR, Piña IL, Leifer ES, Fleg JL, Blackburn G, Fonarow GC, Chase PJ, Piner L, Vest M, O’Connor CM, Ehrman JK, Walsh MN, Ewald G, Bensimhon D, Russell SD; HF-ACTION Investigators. Variables measured during cardiopulmonary exercise testing as predictors of mortality in chronic systolic heart failure [published correction appears in J Am Coll Cardiol. 2016;67:1979–1980]. J Am Coll Cardiol 2016; 67: 780– 789. doi: 10.1016/j.jacc.2015.11.050. 26892413 PMC4761107 sourceNot checked yet

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• cites [191] Shafiq A, Brawner CA, Aldred HA, Lewis B, Williams CT, Tita C, Schairer JR, Ehrman JK, Velez M, Selektor Y, Lanfear DE, Keteyian SJ. Prognostic value of cardiopulmonary exercise testing in heart failure with preserved ejection fraction: the Henry Ford HospITal CardioPulmonary EXercise Testing (FIT-CPX) project. Am Heart J 2016; 174: 167– 172. doi: 10.1016/j.ahj.2015.12.020. 26995385 PMC4804356 sourceNot checked yet

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• cites [192] Guazzi M, Adams V, Conraads V, Halle M, Mezzani A, Vanhees L, Arena R, Fletcher GF, Forman DE, Kitzman DW, Lavie CJ, Myers J. EACPR/AHA scientific statement: clinical recommendations for cardiopulmonary exercise testing data assessment in specific patient populations. Circulation. 2012; 126: 2261– 2274. doi: 10.1161/CIR.0b013e31826fb946. 22952317 PMC4777325 sourceNot checked yet

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• cites [193] Chiarantini D, Volpato S, Sioulis F, Bartalucci F, Del Bianco L, Mangani I, Pepe G, Tarantini F, Berni A, Marchionni N, Di Bari M. Lower extremity performance measures predict long-term prognosis in older patients hospitalized for heart failure. J Card Fail 2010; 16: 390– 395. doi: 10.1016/j.cardfail.2010.01.004. 20447574 sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Ades et al documented a 16% increase in peak VO2 in 60 patients with CAD 65±5 years of age after a 3-month training program; the increase was mediated entirely by enhanced oxygen extraction.

“Ades et al179 documented a 16% increase in peak V˙o2 in 60 patients with CAD 65±5 years of age after a 3-month training program; the increase was mediated entirely by an ΔAV˙o2; that is, enhanced oxygen extraction.”

• cites [179] Ades PA, Waldmann ML, Gillespie C. A controlled trial of exercise training in older coronary patients. J Gerontol A Biol Sci Med Sci 1995; 50A: M7– M11. 7814791 sourceNot checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

Aerobic exercise training can lead to skeletal muscle hypertrophy.

“It has also been shown that aerobic exercise training can lead to skeletal muscle hypertrophy.146”

• cites [146] Konopka AR, Harber MP. Skeletal muscle hypertrophy after aerobic exercise training. Exerc Sport Sci Rev 2014; 42: 53– 61. doi: 10.1249/JES.0000000000000007. 24508740 PMC4523889 sourceNot checked yet

  Not checked in the free run.

May combine two claims.

CVD is likely to occur in older adults who are already functionally impaired, with greater potential to compound functional limitations to the point when ADLs and independence are threatened.

“Therefore, CVD is likely to occur in older adults who are already functionally impaired, with greater potential to compound functional limitations to the point when ADLs and independence are threatened.”

Probably not a substantial claim: may not pass S4 (based). May combine two claims.

Strength training provides synergistic benefit to aerobic exercise, and gains of muscle volume and function may be particularly beneficial in the context of sarcopenia and disease effects on skeletal muscle.

“Strength training provides synergistic benefit to aerobic exercise, and gains of muscle volume and function may be particularly beneficial in the context of sarcopenia and disease effects on skeletal muscle.”

Probably not a substantial claim: may not pass S4 (based).

Older adults with CVD are particularly prone to multimorbidity, frailty, disability associated with hospitalizations, polypharmacy, and other debilitating risks that may make changing physical activity seem overwhelming or hopeless.

“Moreover, older adults with CVD are particularly prone to multimorbidity, frailty, disability associated with hospitalizations, polypharmacy, and other debilitating risks that may make changing physical activity seem overwhelming or hopeless.”

Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing), S4 (based).

Many older adults have led a sedentary lifestyle for so long that the utility of physical activity may no longer seem intuitive or appealing.

“Many older adults have led a sedentary lifestyle for so long that the utility of physical activity may no longer seem intuitive or appealing.”

• AssumptionRests on an assumption: Initiation of physical activity in older adults with CVD presents multiple challenges.

May combine two claims.

Several Cochrane systematic reviews have demonstrated the utility of outpatient phase II CR to reduce mortality and hospital readmissions and to improve QOL.

“Several Cochrane systematic reviews have demonstrated the utility of outpatient phase II CR to reduce mortality and hospital readmissions and to improve QOL.155”

• cites [155] Anderson L, Oldridge N, Thompson DR, Zwisler AD, Rees K, Martin N, Taylor RS. Exercise-based cardiac rehabilitation for coronary heart disease: Cochrane systematic review and meta-analysis. J Am Coll Cardiol 2016; 67: 1– 12. doi: 10.1016/j.jacc.2015.10.044. 26764059 sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Austin et al observed a 16% increase in 6MWT distance and 16% decrease in mean NYHA class in a randomized trial of 200 patients with HFrEF with a mean age of 72 years (34% women) after 24 weeks of combined aerobic/resistance training.

“Similarly, Austin et al195 observed a 16% increase in 6MWT distance and 16% decrease in mean New York Heart Association class in a randomized trial of 200 patients with HFrEF with a mean age of 72 years (34% women) after 24 weeks of combined aerobic/resistance training.”

• cites [195] Austin J, Williams R, Ross L, Moseley L, Hutchison S. Randomised controlled trial of cardiac rehabilitation in elderly patients with heart failure. Eur J Heart Fail 2005; 7: 411– 417. doi: 10.1016/j.ejheart.2004.10.004. 15718182 sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Despite the modest improvement in peak VO2 in HF-ACTION, an 11% reduction in the combined primary end point of all-cause hospitalizations or death occurred over a median follow-up of 30 months.

“Despite this modest improvement in peak V˙o2, an 11% reduction in the combined primary end point of all-cause hospitalizations or death occurred over a median follow-up of 30 months.”

• cites [197] O’Connor CM, Whellan DJ, Lee KL, Keteyian SJ, Cooper LS, Ellis SJ, Leifer ES, Kraus WE, Kitzman DW, Blumenthal JA, Rendall DS, Miller NH, Fleg JL, Schulman KA, McKelvie RS, Zannad F, Piña IL; HF-ACTION Investigators. Efficacy and safety of exercise training in patients with chronic heart failure: HF-ACTION randomized controlled trial. JAMA 2009; 301: 1439– 1450. doi: 10.1001/jama.2009.454. 19351941 PMC2916661 sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Exercise results in a multitude of effects that can delay the progression of atherosclerosis and improve physical function, with reduced inflammation, improved endothelial function, increased insulin sensitivity, and other benefits demonstrated for older patients with CAD, PAD, and stroke.

“Exercise results in a multitude of effects that can delay the progression of atherosclerosis and improve physical function (Tables 2–4151–172); reduced inflammation, improved endothelial function, increased insulin sensitivity, and other benefits have all been demonstrated for older patients with CAD,173,174 peripheral artery disease,175,176 and stroke,177,178 with compounding benefits as function”

• cites 151–172Not checked yet

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• cites [173] Pattyn N, Vanhees L, Cornelissen VA, Coeckelberghs E, De Maeyer C, Goetschalckx K, Possemiers N, Wuyts K, Van Craenenbroeck EM, Beckers PJ. The long-term effects of a randomized trial comparing aerobic interval versus continuous training in coronary artery disease patients: 1-year data from the SAINTEX-CAD study. Eur J Prev Cardiol 2016; 23: 1154– 1164. doi: 10.1177/2047487316631200. 26858279 sourceNot checked yet

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• cites [174] Swardfager W, Herrmann N, Cornish S, Mazereeuw G, Marzolini S, Sham L, Lanctôt KL. Exercise intervention and inflammatory markers in coronary artery disease: a meta-analysis. Am Heart J 2012; 163: 666– 676. e1–3. doi: 10.1016/j.ahj.2011.12.017. 22520533 sourceNot checked yet

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• cites [175] Gardner AW, Parker DE, Montgomery PS, Blevins SM. Stepmonitored home exercise improves ambulation, vascular function, and inflammation in symptomatic patients with peripheral artery disease: a randomized controlled trial. J Am Heart Assoc 2014; 3: e001107. doi: 10.1161/JAHA.114.001107. 25237048 PMC4323792 sourceNot checked yet

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• cites [176] Phillips SA, Mahmoud AM, Brown MD, Haus JM. Exercise interventions and peripheral arterial function: implications for cardiometabolic disease. Prog Cardiovasc Dis 2015; 57: 521– 534. doi: 10.1016/j.pcad.2014.12.005. 25529367 sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S4 (based).

The functional declines that occur with aging are magnified by the development of CVD.

“The functional declines that occur with aging are magnified by the development of CVD.”

May combine two claims.

Cognition changes are often manifest as subtle executive declines, which have been demonstrated to diminish capacity to undertake ADLs and to contribute to a worsening cycle of reduced CRF.

“Cognition changes are often manifest as subtle executive declines, which have been demonstrated to diminish capacity to undertake ADLs183 and to contribute to a worsening cycle of reduced CRF.184”

• cites [183] McLennan SN, Mathias JL, Brennan LC, Russell ME, Stewart S. Cognitive impairment predicts functional capacity in dementia-free patients with cardiovascular disease. J Cardiovasc Nurs 2010; 25: 390– 397. doi: 10.1097/JCN.0b013e3181dae445. 20714236 sourceNot checked yet

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• cites [184] Swardfager W, Herrmann N, Marzolini S, Saleem M, Kiss A, Shammi P, Oh PI, Lanctôt KL. Cardiopulmonary fitness is associated with cognitive performance in patients with coronary artery disease. J Am Geriatr Soc 2010; 58: 1519– 1525. doi: 10.1111/j.1532-5415.2010.02966.x. 20646102 sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Fiatarone et al found that strength increased >100% after several weeks in institutionalized seniors in their 80s and 90s, with many able to reduce dependence on wheelchairs and walkers.

“Fiatarone et al70 analyzed the benefits of strength training in institutionalized seniors in their 80s and 90s and found that strength increased >100% after several weeks, with many able to reduce their dependence on wheelchairs and walkers.”

• cites [70] Fiatarone MA, Marks EC, Ryan ND, Meredith CN, Lipsitz LA, Evans WJ. High-intensity strength training in nonagenarians: effects on skeletal muscle. JAMA 1990; 263: 3029– 3034. 2342214 sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S4 (based).

The use of procedures to increase function such as valve replacements or repairs, pacemakers, or atrial fibrillation ablation becomes less certain amid confounding aspects of the primary disease, comorbidity, frailty, and other clinical complexities.

“The use of procedures to increase function such as valve replacements or repairs, pacemakers, or atrial fibrillation ablation becomes less certain amid confounding aspects of the primary disease, comorbidity, frailty, and other clinical complexities.”

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

Skeletal muscle adaptations to exercise include remodeling of muscle fibers, enhancements to contractile protein and function, mitochondrial biogenesis, increases in skeletal muscle glucose uptake, and improvements in whole-body insulin sensitivity.

“Skeletal muscle adaptations to exercise include remodeling of the muscle fibers, enhancements to contractile protein and function, mitochondrial biogenesis, increases in skeletal muscle glucose uptake, and improvements in whole-body insulin sensitivity.”

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

For many older cardiovascular patients struggling with impending disability and dependency, the focus of muscle strengthening is often to improve mobility such as rising from a chair or walking short distances to maintain independence.

“for many older cardiovascular patients struggling with impending disability and dependency associated with illness and hospitalizations, the focus of muscle strengthening is often to improve mobility such as rising from a chair or walking short distances to maintain independence.”

May combine two claims.

In older patients with HF (mean age ≥70 years), peak VO2 during upright treadmill or cycle exercise is ≈30% lower than in age-matched healthy subjects, and the magnitude of the reduction is independent of HF phenotype.

“Studies by Kitzman et al185 and others186–188 found that in older patients with HF (mean age ≥70 years), peak V˙o2 during upright treadmill or cycle exercise is ≈30% lower than in age-matched healthy subjects, and the magnitude of the reduction is independent of HF phenotype (ejection fraction).186”

• cites [185] Bhella PS, Prasad A, Heinicke K, Hastings JL, Arbab-Zadeh A, Adams-Huet B, Pacini EL, Shibata S, Palmer MD, Newcomer BR, Levine BD. Abnormal haemodynamic response to exercise in heart failure with preserved ejection fraction. Eur J Heart Fail 2011; 13: 1296– 1304. doi: 10.1093/eurjhf/hfr133. 21979991 PMC3220394 sourceNot checked yet

  Not checked in the free run.

• cites [186] Kitzman DW, Little WC, Brubaker PH, Anderson RT, Hundley WG, Marburger CT, Brosnihan B, Morgan TM, Stewart KP. Pathophysiological characterization of isolated diastolic heart failure in comparison to systolic heart failure. JAMA 2002; 288: 2144– 2150. 12413374 sourceNot checked yet

  Not checked in the free run.

• cites [187] Savage PA, Shaw AO, Miller MS, VanBuren P, LeWinter MM, Ades PA, Toth MJ. Effect of resistance training on physical disability in chronic heart failure. Med Sci Sports Exerc 2011; 43: 1379– 1386. doi: 10.1249/MSS.0b013e31820eeea1. 21233772 PMC3410739 sourceNot checked yet

  Not checked in the free run.

• cites [188] Pu CT, Johnson MT, Forman DE, Hausdorff JM, Roubenoff R, Foldvari M, Fielding RA, Singh MA. Randomized trial of progressive resistance training to counteract the myopathy of chronic heart failure. J Appl Physiol (1985) 2001; 90: 2341– 2350. 11356801 sourceNot checked yet

  Not checked in the free run.

May combine two claims.

In the HF-ACTION trial, the mean increase in peak VO2 was only ≈4%, largely because of low training adherence.

“the mean increase in peak V˙o2 was only ≈4%, largely because of low training adherence.197”

• cites [197] O’Connor CM, Whellan DJ, Lee KL, Keteyian SJ, Cooper LS, Ellis SJ, Leifer ES, Kraus WE, Kitzman DW, Blumenthal JA, Rendall DS, Miller NH, Fleg JL, Schulman KA, McKelvie RS, Zannad F, Piña IL; HF-ACTION Investigators. Efficacy and safety of exercise training in patients with chronic heart failure: HF-ACTION randomized controlled trial. JAMA 2009; 301: 1439– 1450. doi: 10.1001/jama.2009.454. 19351941 PMC2916661 sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Cerebral infarcts and neurovascular dysfunction are the most important cerebrovascular pathologies contributing to cognitive impairment and dementia in CVD, and both may benefit from regular physical activity.

“however, cerebral infarcts and neurovascular dysfunction are the most important cerebrovascular pathologies,182 both of which may benefit from regular physical activity.”

• cites [182] Gorelick PB, Scuteri A, Black SE, Decarli C, Greenberg SM, Iadecola C, Launer LJ, Laurent S, Lopez OL, Nyenhuis D, Petersen RC, Schneider JA, Tzourio C, Arnett DK, Bennett DA, Chui HC, Higashida RT, Lindquist R, Nilsson PM, Roman GC, Sellke FW, Seshadri S; on behalf of the American Heart Association Stroke Council, Council on Epidemiology and Prevention, Council on Cardiovascular Nursing, Council on Cardiovascular Radiology and Intervention, and Council on Cardiovascular Surgery and Anesthesia. Vascular contributions to cognitive impairment and dementia: a statement for healthcare professional sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Older adults are even less likely to attend phase II CR, particularly those discharged to a skilled nursing facility or to home care services after hospitalization, despite proven benefits.

“Older adults are even less likely to attend,212 particularly those discharged to a skilled nursing facility (SNF) or to home care services after hospitalization,214 despite proven benefits.215,216”

• cites [212] Balady GJ, Ades PA, Bittner VA, Franklin BA, Gordon NF, Thomas RJ, Tomaselli GF, Yancy CW. Referral, enrollment, and delivery of cardiac rehabilitation/secondary prevention programs at clinical centers and beyond: a presidential advisory from the American Heart Association. Circulation. 2011; 124: 2951– 2960. doi: 10.1161/CIR.0b013e31823b21e2. 22082676 sourceNot checked yet

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• cites [214] Dolansky MA, Moore SM. Older adults’ use of postacute and cardiac rehabilitation services after hospitalization for a cardiac event. Rehabil Nurs 2008; 33: 73– 81. 18330386 sourceNot checked yet

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• cites [215] Menezes AR, Lavie CJ, Forman DE, Arena R, Milani RV, Franklin BA. Cardiac rehabilitation in the elderly. Prog Cardiovasc Dis 2014; 57: 152– 159. doi: 10.1016/j.pcad.2014.01.002. 25216614 sourceNot checked yet

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• cites [216] Leggett LE, Hauer T, Martin BJ, Manns B, Aggarwal S, Arena R, Austford LD, Meldrum D, Ghali W, Knudtson ML, Norris CM, Stone JA, Clement F. Optimizing value from cardiac rehabilitation: a cost-utility analysis comparing age, sex, and clinical subgroups. Mayo Clin Proc 2015; 90: 1011– 1020. doi: 10.1016/j.mayocp.2015.05.015. 26149321 sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Although one of the strongest predictors of enrollment is an endorsement by a physician, many eligible patients, particularly older adults, are simply not referred.

“Although one of the strongest predictors of enrollment is an endorsement by a physician,217 many eligible patients, particularly older adults, are simply not referred.”

• cites [217] Dennis SM, Harris M, Lloyd J, Powell Davies G, Faruqi N, Zwar N. Do people with existing chronic conditions benefit from telephone coaching? A rapid review. Aust Health Rev 2013; 37: 381– 388. doi: 10.1071/AH13005. 23701944 sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

Tai chi may have distinctive value for older adults because it integrates strength, aerobic, and balance components.

“For example, tai chi may have distinctive value for older adults because it integrates strength, aerobic, and balance components.”

Probably not a substantial claim: may not pass S4 (based).

Exercise training is still a daunting challenge for the majority of older patients with CVD.

“Although training strategies and adjuncts to reinforce them continue to evolve, the fact remains that exercise training is still a daunting challenge for the majority of older patients with CVD.”

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

Advances in technology have provided an expanding role for wearable devices in quantifying physical function and activity patterns.

“Advances in technology have provided an expanding role for wearable devices in quantifying physical function and activity patterns.”

Probably not a substantial claim: may not pass S4 (based).

Therapeutic options such as CR and SNFs are surprisingly underdeveloped and underused for functional enhancement in the elderly despite obvious potential.

“Therapeutic options such as CR and SNFs are surprisingly underdeveloped and underused for functional enhancement in the elderly despite obvious potential.”

Probably not a substantial claim: may not pass S2 (checkable), S4 (based).

Current standards of medications and disease management have glaring deficiencies in attention to function and prioritization of interventions to enhance and maintain exercise capacity.

“Current standards of medications and disease management have glaring deficiencies in attention to function and prioritization of interventions to enhance and maintain exercise capacity.”

Probably not a substantial claim: may not pass S4 (based).

Numerous tests have been developed that are easily applied and reflect combinations of strength, balance, mobility, and frailty that quantify a senior's ability to function independently and avoid falls, disability, or hospitalization.

“Numerous tests have been developed that are easily applied and that reflect combinations of strength, balance, mobility, and frailty that quantify a senior’s ability to function independently and avoid falls, disability, or hospitalization.”

May combine two claims.

A large and growing body of literature has demonstrated that older adults respond favorably to exercise training programs, with relative changes in function similar to those in younger adults.

“A large and growing body of literature has demonstrated that older adults respond favorably to exercise training programs, with relative changes in function similar to those in younger adults.”

May combine two claims.

Current SNF rehabilitation does not adequately address deficits in physical function, which directly contributes to poor outcomes, including low community discharge rates of only 28%.

“Current SNF rehabilitation does not adequately address deficits in physical function, which directly contributes to poor outcomes (low community discharge rates of only 28%231).”

• cites [231] Skilled Nursing Facility Services 2013: 157– 184. http://www.medpac.gov/docs/default-source/reports/chapter-8-skilled-nursing-facility-services-march-2015-report-pdf?sfvrsn=0. Accessed May 15, 2016.Not checked yet

  Not checked in the free run.

May combine two claims.

Transitional and home-based phase II CR models have been shown to be effective and safe, although they are not standardized and often not reimbursed by insurance.

“Transitional and home-based phase II CR models have been shown to be effective and safe,219–222 although they are not standardized and often not reimbursed by insurance.”

• cites [219] Cowie A, Thow MK, Granat MH, Mitchell SL. A comparison of home and hospital-based exercise training in heart failure: immediate and long-term effects upon physical activity level. Eur J Cardiovasc Prev Rehabil 2011; 18: 158– 166. doi: 10.1177/1741826710389389. 21450662 sourceNot checked yet

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• cites [220] Kraal JJ, Peek N, Van den Akker-Van Marle ME, Kemps HM. Effects of home-based training with telemonitoring guidance in low to moderate risk patients entering cardiac rehabilitation: short-term results of the FIT@Home study. Eur J Prev Cardiol 2014; 21(suppl): 26– 31. doi: 10.1177/2047487314552606. 25354951 sourceNot checked yet

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• cites [221] Ramadi A, Haennel RG, Stone JA, Arena R, Threlfall TG, Hitt E, Aggarwal SG, Haykowsky M, Martin BJ. The sustainability of exercise capacity changes in home versus center-based cardiac rehabilitation. J Cardiopulm Rehabil Prev 2015; 35: 21– 28. doi: 10.1097/HCR.0000000000000084. 25313452 sourceNot checked yet

  Not checked in the free run.

• cites [222] Scane K, Alter D, Oh P, Brooks D. Adherence to a cardiac rehabilitation home program model of care: a comparison to a well-established traditional on-site supervised program. Appl Physiol Nutr Metab 2012; 37: 206– 213. doi: 10.1139/h11-151. 22360343 sourceNot checked yet

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May combine two claims.

Although peak VO2 is the gold standard for assessing CRF and often the primary efficacy measure for interventions in CVD, it is not always readily available, nor is it the best metric for many older individuals.

“Although the gold standard for assessing CRF, peak V˙o2, has a well-established history and is often the primary efficacy measure for interventions in CVD, it is not always readily available, nor is it the best metric for many older individuals.”

May combine two claims.

Although 70% of older adults who use SNFs are eligible for some type of CR, there typically are no standard cardiac assessments and no cardiac education delivered in these facilities, as well as no specific mechanisms to facilitate CR once patients leave SNFs and return to the community.

“Although 70% of older adults who use SNFs are eligible for some type of CR, there typically are no standard cardiac assessments and no cardiac education delivered in these facilities,241 as well as no specific mechanisms to facilitate CR once patients leave SNFs and return to the community.”

• cites [241] Dolansky MA, Zullo MD, Hassanein S, Schaefer JT, Murray P, Boxer R. Cardiac rehabilitation in skilled nursing facilities: a missed opportunity. Heart Lung 2012; 41: 115– 124. doi: 10.1016/j.hrtlng.2011.08.006. 22054718 PMC3288539 sourceNot checked yet

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• AssumptionRests on an assumption: There is little disease-specific research in SNFs with regard to physical function.

May combine two claims.

High-intensity interval training requires close supervision, and its utility for broader application to older adults is still unproven.

“However, high-intensity interval training entails short bursts of high-intensity aerobic exercise with longer periods of lower-intensity training that requires close supervision, and its utility for broader application to older adults is still unproven.”

May combine two claims.

The consequences of functional impairment in older adults with CVD include increased morbidity and mortality and reduced ability to perform ADLs, remain independent, and delay disability.

“The consequences of functional impairment in older adults with CVD include increased morbidity and mortality and reduced ability to perform ADLs, remain independent, and delay disability.”

Probably not a substantial claim: may not pass S3 (load-bearing).

High-intensity interval training has been suggested for its training efficacy in older, vulnerable patients with CVD.

“High-intensity interval training has also been suggested for its training efficacy in older, vulnerable patients with CVD.178”

• cites [178] Takatori K, Matsumoto D, Okada Y, Nakamura J, Shomoto K. Effect of intensive rehabilitation on physical function and arterial function in community-dwelling chronic stroke survivors. Top Stroke Rehabil 2012; 19: 377– 383. doi: 10.1310/tsr1905-377. 22982824 sourceNot checked yet

  Not checked in the free run.

May combine two claims.

For patients able to return home from an SNF, impaired physical function often persists as a poorly addressed component of failing health, rehospitalization, or death.

“Similarly, for those patients who are able to return home from an SNF, impaired physical function often persists as a poorly addressed component of failing health,232–234 rehospitalization,233,234 or death.235”

• cites [232] Portegijs E, Buurman BM, Essink-Bot ML, Zwinderman AH, de Rooij SE. Failure to regain function at 3 months after acute hospital admission predicts institutionalization within 12 months in older patients. J Am Med Dir Assoc 2012; 13: 569.e1– 569.e7. doi: 10.1016/j.jamda.2012.04.003. 22572555 sourceNot checked yet

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• cites [233] Hoyer EH, Needham DM, Atanelov L, Knox B, Friedman M, Brotman DJ. Association of impaired functional status at hospital discharge and subsequent rehospitalization. J Hosp Med 2014; 9: 277– 282. doi: 10.1002/jhm.2152. 24616216 PMC4347875 sourceNot checked yet

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• cites [234] Hoyer EH, Needham DM, Miller J, Deutschendorf A, Friedman M, Brotman DJ. Functional status impairment is associated with unplanned readmissions. Arch Phys Med Rehabil 2013; 94: 1951– 1958. doi: 10.1016/j.apmr.2013.05.028. 23810355 PMC6140789 sourceNot checked yet

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• cites [235] Baztán JJ, Gálvez CP, Socorro A. Recovery of functional impairment after acute illness and mortality: one-year follow-up study. Gerontology 2009; 55: 269– 274. doi: 10.1159/000193068. 19141990 sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Outpatient phase II CR achieved a 20% to 31% reduction in mortality from CAD, along with improved functional capacity, reduced risk factors, improved emotional health and QOL, and improved cognition.

“Outpatient phase II CR achieved a 20% to 31% reduction in mortality from CAD, along with improved functional capacity,208 reduced risk factors, improved emotional health and QOL,209 and improved cognition.210”

• cites [208] Jolliffe JA, Rees K, Taylor RS, Thompson D, Oldridge N, Ebrahim S. Exercise-based rehabilitation for coronary heart disease. Cochrane Database Syst Rev 2000: CD001800. 11034729Not checked yet

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• cites [209] Strong PC, Lee SH, Chou YC, Wu MJ, Hung SY, Chou CL. Relationship between quality of life and aerobic capacity of patients entering phase II cardiac rehabilitation after coronary artery bypass graft surgery. J Chin Med Assoc 2012; 75: 121– 126. doi: 10.1016/j.jcma.2012.02.005. 22440270 sourceNot checked yet

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• cites [210] Gunstad J, Macgregor KL, Paul RH, Poppas A, Jefferson AL, Todaro JF, Cohen RA. Cardiac rehabilitation improves cognitive performance in older adults with cardiovascular disease. J Cardiopulm Rehabil 2005; 25: 173– 176. 15931022 PMC3226758 sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Older individuals now constitute the predominant population of individuals with CVD, and functional impairment is a predictable consequence, particularly because CVD compounds the functional deficits associated with aging.

“Older individuals now constitute the predominant population of individuals with CVD; functional impairment is a predictable consequence, particularly because CVD compounds the functional deficits associated with aging.”

May combine two claims.

Other common impediments to CR enrollment and participation include illness severity, complications during hospitalization, impaired cognitive or physical function, depression, pain, lack of social support, and logistic barriers.

“Other common impediments to CR enrollment and participation include illness severity, complications during hospitalization, impaired cognitive or physical function, depression, pain, lack of social support, and logistic barriers.218”

• cites [218] Dolansky MA, Xu F, Zullo M, Shishehbor M, Moore SM, Rimm AA. Post-acute care services received by older adults following a cardiac event: a population-based analysis. J Cardiovasc Nurs 2010; 25: 342– 349. doi: 10.1097/JCN.0b013e3181c9fbca. 20539168 PMC2885047 sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

Measurement of gait speed is even simpler than the SPPB to administer and is also effective.

“Measurement of gait speed is even simpler than the SPPB to administer and is also effective.”

May combine two claims.

Measurements including strength and balance are important metrics of function and in many cases more strongly determine an older individual's ability to remain independent, continue working, or safely perform ADLs than maximal exercise tolerance.

“Measurements including strength and balance are also important metrics of function and in many cases more strongly determine an older individual’s ability to remain independent, continue working, or safely perform ADLs than maximal exercise tolerance.”

Probably not a substantial claim: may not pass S4 (based). May combine two claims.

Despite the fact that older adults stand to benefit considerably from rehabilitation programs, both their referral and participation rates are lower than those in younger adults.

“Unfortunately, despite the fact that older adults stand to benefit considerably from rehabilitation programs, both their referral and participation rates are lower than those in younger adults.”

Probably not a substantial claim: may not pass S4 (based).

Current standards of evidence-based medications often manifest greater functional risks than anticipated benefits in the elderly.

“Moreover, current standards of evidence-based medications often manifest greater functional risks than anticipated benefits in the elderly.”

Classified as probably not a substantial claim.

Encouragement to make a bed, carry laundry, climb stairs, dance, or walk as part of a daily routine may better achieve healthful physically active behavior in many older adults.

“Encouragement to make a bed, carry laundry, climb stairs, dance, or walk as part of a daily routine may better achieve healthful physically active behavior in many older adults.”

May combine two claims.

Even when referred, fewer older adults actually enroll; many cite logistic, psychosocial, and financial impediments.

“Furthermore, even when they are referred, fewer older adults actually enroll; many cite logistic, psychosocial, and financial impediments.212”

• cites [212] Balady GJ, Ades PA, Bittner VA, Franklin BA, Gordon NF, Thomas RJ, Tomaselli GF, Yancy CW. Referral, enrollment, and delivery of cardiac rehabilitation/secondary prevention programs at clinical centers and beyond: a presidential advisory from the American Heart Association. Circulation. 2011; 124: 2951– 2960. doi: 10.1161/CIR.0b013e31823b21e2. 22082676 sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Novel programs using mobile technology or telehealth and home-based programs may increase accessibility and improve adherence and have been demonstrated to be as effective as traditional center-based programs.

“Novel programs using mobile technology or telehealth and home-based programs may increase accessibility to participants and improve adherence and have been demonstrated to be as effective as traditional center-based programs.”

May combine two claims.

Gait speeds at SNF discharge averaged 0.39 m/s, which is less than half of the 1.0 m/s necessary for community ambulation.

“Notably, gait speeds at SNF discharge averaged 0.39 m/s,239 which is less than half of the 1.0 m/s necessary for community ambulation.240”

• cites [239] Lenze EJ, Host HH, Hildebrand MW, Morrow-Howell N, Carpenter B, Freedland KE, Baum CA, Dixon D, Doré P, Wendleton L, Binder EF. Enhanced medical rehabilitation increases therapy intensity and engagement and improves functional outcomes in postacute rehabilitation of older adults: a randomized-controlled trial. J Am Med Dir Assoc 2012; 13: 708– 712. doi: 10.1016/j.jamda.2012.06.014. 22863663 PMC3601780 sourceNot checked yet

  Not checked in the free run.

• cites [240] Fritz S, Lusardi M. White paper: “walking speed: the sixth vital sign” [published correction appears in J Geriatr Phys Ther. 2009;32:110]. J Geriatr Phys Ther 2009; 32: 46– 49. 20039582 sourceNot checked yet

  Not checked in the free run.

Classified as probably not a substantial claim.

There is no specific guideline that dictates a schedule of assessments for older patients with CVD.

“There is no specific guideline that dictates a schedule of assessments for older patients with CVD, but clinical management provides many logical considerations.”

Probably not a substantial claim: may not pass S4 (based). May combine two claims.

The SPPB and Montreal Cognitive Assessment tests are easily administered in an office setting and provide relatively sensitive measures of longitudinal changes.

“The SPPB and Montreal Cognitive Assessment tests are easily administered in an office setting and provide relatively sensitive measures of longitudinal changes.”

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

Relatively simpler emphasis on increasing physical activity is often more successful than formal exercise training.

“Relatively simpler emphasis on increasing physical activity is often more successful than formal exercise training.”

May combine two claims.

Evidence suggests that patients in rehabilitation at SNF settings are ≈80% less active compared with community-dwelling older adults, and they do not engage in an adequate intensity of rehabilitation to facilitate meaningful improvements in physical function.

“Evidence suggests that patients in rehabilitation at SNF settings are ≈80% less active compared with community-dwelling older adults, and they do not engage in an adequate intensity of rehabilitation to facilitate meaningful improvements in physical function.236–238”

• cites [236] Peiris CL, Taylor NF, Shields N. Additional Saturday allied health services increase habitual physical activity among patients receiving inpatient rehabilitation for lower limb orthopedic conditions: a randomized controlled trial. Arch Phys Med Rehabil 2012; 93: 1365– 1370. doi: 10.1016/j.apmr.2012.03.004. 22446517 sourceNot checked yet

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• cites [237] Peiris CL, Taylor NF, Shields N. Patients receiving inpatient rehabilitation for lower limb orthopaedic conditions do much less physical activity than recommended in guidelines for healthy older adults: an observational study. J Physiother 2013; 59: 39– 44. doi: 10.1016/S1836-9553(13)70145-0. 23419914 sourceNot checked yet

  Not checked in the free run.

• cites [238] Grant PM, Granat MH, Thow MK, Maclaren WM. Analyzing free-living physical activity of older adults in different environments using body-worn activity monitors. J Aging Phys Act 2010; 18: 171– 184. 20440029 sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Low participation of older adults in outpatient phase II CR programs has been attributed to multimorbidity, baseline frailty, and disability, but patients with these features particularly benefit from CR.

“Paradoxically, low participation of older adults in outpatient phase II CR programs has been attributed to multimorbidity, baseline frailty, and disability (such that CR seems particularly daunting), but patients with these features particularly benefit from CR.”