Lifelong endurance exercise and its relation with coronary atherosclerosis

In the paper

“Some studies have shown that endurance exercise reduces the risk for ischaemic events regardless of CAC score, and this reduction is greatest at the higher CAC scores.24,26”

What the sources say

• Disputed

  The Results (Overall Relationship Between PA, CAC and Cardiovascular Outcomes) report fewer incident CVD events with higher physical activity only for participants with CAC <100 AU; they state there was no significant association with CVD for participants with CAC ≥100 AU. The Discussion describes the largest risk differences at high CAC in another analysis, but those differences concerned mortality, not ischaemic events. (LLM, conf=0.88)

  Checked by a reasoning model — may be wrong.

  cites [24] German, 2022, Physical activity, coronary artery calcium, and cardiovascular outcomes in the Multi-Ethnic Study of Atherosclerosis (MESA), Med Sci Sports Exerc sourceExperimental — accuracy not yet measured
• Partly supported

  The Abstract reports lower CVD event risk with higher cardiorespiratory fitness at all CAC levels, and the Discussion reports a stronger inverse association as CAC burden increased. But this observational study of generally healthy men did not test whether endurance exercise itself reduces ischaemic events; the Clinical Implications section explicitly says it did not examine the effect of changes in fitness on CVD risk. (LLM, conf=0.88)

  cites [26] Radford, 2018, Cardiorespiratory fitness, coronary artery calcium, and cardiovascular disease events in a cohort of generally healthy middle-age men: results from the Cooper Center Longitudinal Study, Circulation sourceExperimental — accuracy not yet measured

In the paper

“Regular exercise improves blood pressure control and lipid profiles, reduces the incidence of diabetes and myocardial infarction, and increases life expectancy.6–9”

What the sources say

• Partly supported

  The Perspectives and Discussion sections report improved blood pressure and HDL cholesterol with endurance training; triglycerides tended to decrease. The Discussion also describes an association between physical activity and lower cardiovascular mortality, but the paper does not establish reduced diabetes or myocardial-infarction incidence or increased life expectancy. Page numbers are not available in our copy. (LLM, conf=0.88)

  cites [6] Cornelissen, 2005, Effects of endurance training on blood pressure, blood pressure-regulating mechanisms, and cardiovascular risk factors, Hypertension sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [7] Kelley, 2006, Aerobic exercise and lipids and lipoproteins in patients with cardiovascular disease: a meta-analysis of randomized controlled trials, J Cardiopulm Rehabil source
• Partly supported

  The Results (page unavailable) report that exercise lowered plasma triglycerides in people with type 2 diabetes, supporting only part of the lipid-profile claim; they found no significant improvement in cholesterol or blood pressure. The review did not assess diabetes incidence, myocardial infarction incidence, or mortality, so it cannot support the claimed reductions in incidence or increase in life expectancy. (LLM, conf=0.91)

  cites [8] Thomas, 2006, Exercise for type 2 diabetes mellitus, Cochrane Database Syst Rev sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [9] Koolhaas, 2016, Physical activity types and coronary heart disease risk in middle-aged and elderly persons: the Rotterdam study, Am J Epidemiol source

In the paper

“meaning that the plaque-to-vessel ratio in athletes could be lower and thus lead to less significant stenosis.27,28”

What the sources say

• ?Not checked — no full text of the sourcecites [27] Parker, 1994, Effects of exercise training on regulation of tone in coronary arteries and arterioles, Med Sci Sports Exerc source
• Supported

  In “Coronary Artery Size Before Nitroglycerin” (page unavailable), the paper reports an autopsy finding that physically active Masai men had as much coronary atherosclerosis as US men but patent arterial lumens because their vessels were larger. That supports the citing sentence’s hedged suggestion that plaque could cause less consequential narrowing in athletes; the paper does not present it as a measured plaque-to-vessel ratio in its runners. (LLM, conf=0.84)

  cites [28] Haskell, 1993, Coronary artery size and dilating capacity in ultradistance runners, Circulation source

In the paper

“In 2017, two other studies added a relevant nuance that athletes presenting with coronary plaques were more likely to have calcified plaques, whereas non-athletes with plaques more frequently had mixed plaques.3,4”

What the sources say

• ?Not checked — no full text of the sourcecites [3] Merghani, 2017, Prevalence of subclinical coronary artery disease in masters endurance athletes with a low atherosclerotic risk profile, Circulation source
• Partly supported

  The Results (p. 13) report fewer mixed plaques and more exclusively calcified plaques among plaque-bearing athletes in the most active group than in the least active group. But the comparison was between groups of athletes, not between athletes and non-athletes; the Accelerated Coronary Artery Calcification section (p. 15) says even the least active group averaged about one hour of running per week. (LLM, conf=0.90)

  cites [4] Aengevaeren, 2017, Relationship between lifelong exercise volume and coronary atherosclerosis in athletes, Circulation sourceExperimental — accuracy not yet measured

In the paper

“Increased cardiorespiratory fitness is associated with a progressive reduction of cardiovascular events, which would seem to be at odds with the aforementioned link between lifelong exercise load and increased coronary atherosclerosis.”

What the sources say

• Supported

  The Discussion (page unavailable) reports that prospective epidemiological studies find physical activity and fitness inversely related to cardiovascular disease incidence and mortality. That supports the claimed association between greater fitness and fewer cardiovascular events; the paper reports this as background evidence, not as an outcome measured in its training analysis. (LLM, conf=0.87)

  cites [6] Cornelissen, 2005, Effects of endurance training on blood pressure, blood pressure-regulating mechanisms, and cardiovascular risk factors, Hypertension source
• ?Not checked — no full text of the sourcecites [7] Kelley, 2006, Aerobic exercise and lipids and lipoproteins in patients with cardiovascular disease: a meta-analysis of randomized controlled trials, J Cardiopulm Rehabil source
• ?Could not verify

  The Results (page unavailable) report fitness outcomes but say that no study included diabetic complications as an outcome; the Discussion (page unavailable) says the trials were too short to report significant long-term complications. Searches for cardiovascular events and fitness-related cardiovascular risk found no passage establishing a progressive reduction in events as fitness increases. (LLM, conf=0.76)

  cites [8] Thomas, 2006, Exercise for type 2 diabetes mellitus, Cochrane Database Syst Rev sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [9] Koolhaas, 2016, Physical activity types and coronary heart disease risk in middle-aged and elderly persons: the Rotterdam study, Am J Epidemiol source

In the paper

“The SSS and SIS have demonstrated clinical validity in detecting major adverse cardiac events in multiple populations.15–19”

What the sources say

• Partly supported

  The Multivariable Cox models section reports that adding SSS or SIS improved prediction of death or myocardial infarction, and Table 3 shows improved C-statistics for both scores. The evidence comes from one multicenter cohort of symptomatic patients with suspected coronary artery disease, not multiple distinct populations; the measured endpoint was all-cause mortality or non-fatal MI. (LLM, conf=0.84)

  cites [15] Al-Mallah, 2014, Does coronary CT angiography improve risk stratification over coronary calcium scoring in symptomatic patients with suspected coronary artery disease? Results from the prospective multicenter international CONFIRM registry, Eur Heart J Cardiovasc Imaging sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [16] Tesche, 2016, Prognostic implications of coronary CT angiography-derived quantitative markers for the prediction of major adverse cardiac events, J Cardiovasc Comput Tomogr source
• ?Not checked — no full text of the sourcecites [17] Nadjiri, 2016, Prognostic value of coronary CT angiography in diabetic patients: a 5-year follow up study, Int J Cardiovasc Imaging source
• Partly supported

  The Prediction all-cause mortality section reports that both SSS and SIS predicted five-year all-cause mortality in patients with suspected coronary artery disease. It does not report their performance for major adverse cardiac events or establish validity across multiple populations; the Study limitations section says cardiac-specific endpoints were unavailable for all centres. (LLM, conf=0.88)

  cites [18] Motwani, 2017, Machine learning for prediction of all-cause mortality in patients with suspected coronary artery disease: a 5-year multicentre prospective registry analysis, Eur Heart J sourceExperimental — accuracy not yet measured
• Supported

  Section 3.3.1 reports that all semiquantitative CCTA risk scores, including SIS and SSS, independently predicted events in patients with and without diabetes. The Discussion identifies the endpoint as all-cause death and non-fatal myocardial infarction, supporting the claim across these two patient groups. (LLM, conf=0.91)

  cites [19] van den Hoogen, 2020, Coronary atherosclerosis scoring with semiquantitative CCTA risk scores for prediction of major adverse cardiac events: propensity score-based analysis of diabetic and non-diabetic patients, J Cardiovasc Comput Tomogr source

In the paper

“Since calcified plaques are more stable and less prone to rupture than mixed and non-calcified plaques”

What the sources say

• Partly supported

  The Discussion (page unavailable) reports significantly higher three-year major adverse cardiac event rates for noncalcified and mixed plaques than for calcified plaques, and describes soft, lipid-filled plaques as more vulnerable. The study does not establish that calcified plaques are mechanically more stable or specifically less prone to rupture; it measured clinical events, not plaque rupture. (LLM, conf=0.86)

  cites [20] Hou, 2012, Prognostic value of coronary CT angiography and calcium score for major adverse cardiac events in outpatients, JACC Cardiovasc Imaging sourceExperimental — accuracy not yet measured

In the paper

“it is known that endurance athletes have larger coronary arteries and a greater vasodilatory potential”

What the sources say

• ?Not checked — no full text of the sourcecites [27] Parker, 1994, Effects of exercise training on regulation of tone in coronary arteries and arterioles, Med Sci Sports Exerc source
• Partly supported

  The Abstract reports greater coronary-artery dilation after nitroglycerin in the ultradistance runners. It also reports no significant difference in artery size before nitroglycerin, so the unqualified claim that endurance athletes have larger coronary arteries is not supported by this study's measurements. (LLM, conf=0.90)

  cites [28] Haskell, 1993, Coronary artery size and dilating capacity in ultradistance runners, Circulation sourceExperimental — accuracy not yet measured

In the paper

“these prior studies only looked at the relative distribution of plaque type in individuals with evidence of plaque, but differences in the absolute prevalence of calcified, mixed, and non-calcified plaques were not reported.”

What the sources say

• ?Not checked — no full text of the sourcecites [3] Merghani, 2017, Prevalence of subclinical coronary artery disease in masters endurance athletes with a low atherosclerotic risk profile, Circulation source
• Supported

  The Results (pp. 13–14) compare plaque types among participants who already had coronary atherosclerosis. The plaque-type percentages in Supplemental Table 1 (p. 46) likewise use participants with plaque as their denominator; the paper does not report differences in the absolute prevalence of each plaque type across all participants. (LLM, conf=0.87)

  cites [4] Aengevaeren, 2017, Relationship between lifelong exercise volume and coronary atherosclerosis in athletes, Circulation source

In the paper

“All coronary lesions were interpreted following the 2016 SCCT guidelines for their location, stenosis grade, composition (calcified, mixed, and non-calcified) as well as their vulnerability (positive remodeling, low-attenuation plaque, spotty calcification, and the napkin-ring sign).12,13”

What the sources say

• Partly supported

  The CAD-RADS stenosis grading table gives stenosis categories, and Figure 2 identifies lesion locations and calcified plaque. The modifier V passage lists all four vulnerability features in the claim, but specifies that at least two are needed to designate a plaque high-risk. The passages do not establish the claimed three-part composition classification, particularly the mixed-plaque category. (LLM, conf=0.84)

  cites [12] Cury, 2016, Coronary Artery Disease - Reporting and Data System (CAD-RADS): an expert consensus document of SCCT, ACR and NASCI: endorsed by the ACC, JACC Cardiovasc Imaging sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [13] Hecht, 2017, 2016 SCCT/STR guidelines for coronary artery calcium scoring of noncontrast noncardiac chest CT scans: a report of the Society of Cardiovascular Computed Tomography and Society of Thoracic Radiology, J Cardiovasc Comput Tomogr source

In the paper

“The non-calcified/mixed characteristics, a stenosis grade of ≥50%, and the proximal location of coronary plaques are all established risk factors for ischaemic heart disease.14,21”

What the sources say

• ?Not checked — no full text of the sourcecites [14] Min, 2007, Prognostic value of multidetector coronary computed tomographic angiography for prediction of all-cause mortality, J Am Coll Cardiol source
• Partly supported

  The Results and Discussion (page unavailable) support ≥50% stenosis as a predictor of acute coronary syndrome and associate specific high-risk plaque features, including low attenuation, with it. They do not establish non-calcified or mixed composition as such a risk factor, nor do they address proximal plaque location. The study’s finding in patients with acute chest pain is also narrower than a general claim about ischaemic heart disease. (LLM, conf=0.87)

  cites [21] Puchner, 2014, High-risk plaque detected on coronary CT angiography predicts acute coronary syndromes independent of significant stenosis in acute chest pain: results from the ROMICAT-II trial, J Am Coll Cardiol sourceExperimental — accuracy not yet measured

In the paper

“our non-athletes exhibited a higher level of fitness with a higher METmin/week than the controls by Aengevaeren et al. (888 vs. 669 METmin/week) and a greater average percentage predicted VO2peak of 122% compared to 96% reported by Merghani et al.3,4”

What the sources say

• ?Not checked — no full text of the sourcecites [3] Merghani, 2017, Prevalence of subclinical coronary artery disease in masters endurance athletes with a low atherosclerotic risk profile, Circulation source
• Partly supported

  The Exercise volume patterns table (p. 34) reports 669 [405–802] MET-min/week for Aengevaeren et al.’s lowest-exercise group, supporting the numerical comparison. But the Study population (p. 7) identifies participants as recreational or competitive athletes, and the Limitations (p. 19) explicitly say the study had no non-athlete control group. The VO2peak figure is attributed to Merghani et al., not this source. (LLM, conf=0.88)

  cites [4] Aengevaeren, 2017, Relationship between lifelong exercise volume and coronary atherosclerosis in athletes, Circulation sourceExperimental — accuracy not yet measured

In the paper

“In the paper by Merghani et al. and Molhenkamp et al., athletes were mostly engaged in running whilst the athletic population in the trial by Aengevaeren et al. was more diverse with 29% cyclists and 25% runners.2–4”

What the sources say

• ?Not checked — no full text of the sourcecites [2] Mohlenkamp, 2008, Running: the risk of coronary events: prevalence and prognostic relevance of coronary atherosclerosis in marathon runners, Eur Heart J source
• ?Not checked — no full text of the sourcecites [3] Merghani, 2017, Prevalence of subclinical coronary artery disease in masters endurance athletes with a low atherosclerotic risk profile, Circulation source
• Supported

  Supplemental Table 1 (pp. 40–41) lists a range of sports and reports cycling as the dominant sport for 81 participants (29%) and running for 72 (25%). These figures support the part of the sentence attributed to Aengevaeren et al.; they refer to dominant sport, not all participation in each sport. (LLM, conf=0.94)

  cites [4] Aengevaeren, 2017, Relationship between lifelong exercise volume and coronary atherosclerosis in athletes, Circulation source

In the paper

“vulnerable plaques, which carry the highest risk for events, were rare and not associated with an athletic lifestyle.”

In the paper

“There was no difference in the hours per week of endurance exercise between lifelong and late-onset athletes, but both athlete groups performed more hours than controls [11 h/week (10–14) vs. 10 h/week (8–12) vs. 1 h/week (0–3)].”

In the paper

“lifelong middle-aged athletes had more coronary plaques, including more unstable non-calcified plaques in proximal segments”

• Also stated in: § Conclusion · plain

  “Lifelong middle-aged athletes had more coronary plaques, including more non-calcified and mixed plaques and plaques in proximal segments with significant luminal stenosis, than fit and healthy individuals with a similarly low cardiovascular risk profile.”

In the paper

“Controls had a higher body fat percentage than lifelong and late-onset athletes (19.4% vs. 13.9% vs. 15%).”

In the paper

“a greater proportion of lifelong athletes had proximal plaques and lesions with significant stenosis, as well as plaques of non-calcified and mixed morphology.”

In the paper

“Lifelong and late-onset had a similar VO2peak which was significantly higher than in controls [VO2peak 48 mL/min/kg (43–53) vs. 46 mL/min/kg (41–51) vs. 37 mL/min/kg (32–42); % predicted VO2peak 159% (143–177) vs. 155% (138–169) vs. 122% (108–138)].”

• Also stated in: § Methods and results · plain

  “Lifelong and late-onset athletes had higher peak oxygen uptake than non-athletes [159 (143–177) vs. 155 (138–169) vs. 122 (108–138) % predicted].”

In the paper

“whilst we did observe an increased plaque burden in lifelong athletes (i.e. SSS >0–5 and SIS >0–3), this did not extend beyond an SSS >10 or SIS >6 meaning that the overall plaque burden remains low in athletes.”

In the paper

“controls had a higher body weight leading to a higher BMI than lifelong and late-onset athletes (24.0 vs. 23.2 vs. 23.5 kg/m²).”

In the paper

“In the Master@Heart study, cyclists represented the largest group within the athlete population, whereas active controls were mostly engaged in running.”

In the paper

“Lifelong and late-onset athletes from the Master@Heart study performed more training hours per week and had a higher METmin/week with a higher VO2peak than in other studies.”

In the paper

“lifetime intensive endurance training increases the overall coronary atherosclerotic burden with more plaques, including non-calcified and mixed plaques, plaques in proximal segments, and those with a significant degree of stenosis.”

In the paper

“Sampling was however stratified by current age (45–53, 54–62, and 63–70 years).”

In the paper

“Lifelong endurance athletes had more coronary plaques, including more non-calcified plaques in proximal segments, than fit and healthy individuals with a similarly low cardiovascular risk profile.”

In the paper

“carefully stratified for age and exercise exposure”

In the paper

“The mean age of all participants was 56 ± 6 years and was similar amongst all groups.”

In the paper

“Previous studies have investigated the dose–response relationship between exercise and coronary artery disease and reported a higher CAC burden in healthy marathon runners compared to risk-factor matched non-athletes.2”

What the sources say

• ?Not checked — no full text of the sourcecites [2] Mohlenkamp, 2008, Running: the risk of coronary events: prevalence and prognostic relevance of coronary atherosclerosis in marathon runners, Eur Heart J source

In the paper

“The widths of CIs have not been adjusted for multiplicity, and therefore the intervals should not be used to infer definitive exercise effects on primary outcomes.”

In the paper

“Systolic blood pressure, diastolic blood pressure, total cholesterol, LDL cholesterol, and HbA1c were similar in all groups.”

In the paper

“multiple linear and logistic regression analysis that adjusted for age, body mass index (BMI), systolic and diastolic blood pressure, total cholesterol, low-density lipoprotein (LDL) cholesterol, glycated haemoglobin (HbA1c), and family history of coronary artery disease”

• Also stated in: § Methods and results · plain

  “Analyses were corrected for multiple cardiovascular risk factors.”

In the paper

“There were no missing data from population characteristics, exercise testing, and CTCA in any group.”

In the paper

“From all eligible subjects, 605 were sampled at random for inclusion to minimize the risk of selection bias.”

In the paper

“Computed tomography coronary angiography interpreters were blinded to the athletic background of the study participants and to the other study examinations.”

In the paper

“The family incidence of coronary artery disease was 6.3% in lifelong athletes, 6.8% in late-onset athletes, and 6.3% in controls.”

In the paper

“All participants of the Master@Heart study were of White ethnicity, so our results may not be extrapolated to other ethnicities.”

In the paper

“All athletes denied using illicit performance-enhancing drugs that might induce or accelerate coronary atherosclerosis. However, no laboratory tests were performed to exclude this possibility.”

In the paper

“The Master@Heart study was limited to male individuals and did not provide insights on the exercise dose–response relationship in women.”

In the paper

“Our data demonstrate that a healthy lifestyle and above-average cardiorespiratory training and fitness prevents coronary atherosclerosis with a more favourable pattern of more calcified and less mixed or non-calcified plaques.”

In the paper

“We cannot exclude that some athletes may have temporarily interrupted exercise training during their lifetime.”

In the paper

“This stringent process enabled us to include study participants at random, thereby diminishing the possibility of including individuals who registered because of personal health concerns.”

In the paper

“lifetime training load was assessed using questionnaires rather than continuous tracking of training logs over time.”

In the paper

“a higher VO2peak is associated with a lower lipid volume, higher fibrous volume, and thicker fibrous cap in coronary plaques”

What the sources say

• ?Not checked — no full text of the sourcecites [30] Yoshikawa, 2013, Association of cardiorespiratory fitness with characteristics of coronary plaque: assessment using integrated backscatter intravascular ultrasound and optical coherence tomography, Int J Cardiol source

In the paper

“The primary endpoint from the Master@Heart study was investigated in a cross-sectional design. Therefore, a definitive causal relationship between endurance exercise and coronary artery disease cannot be made.”

In the paper

“superior aerobic capacity and lowest body fat percentage provide indirect evidence of superior training levels in the athletic population.”

In the paper

“Multiple comparisons were performed between lifelong athletes, late-onset athletes, and controls which may increase the risk of Type 1 errors.”

In the paper

“we do not believe that the higher prevalence of coronary plaques in athlete was influenced by occult arterial hypertension or dyslipidaemia as blood pressure was similar between groups and athletes had even more favourable lipid profiles than controls.”

In the paper

“we did not perform blood sampling or blood pressure monitoring prior to study inclusion.”