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Prevention of Cardiovascular Disease in Persons with Type 2 Diabetes Mellitus: Current Knowledge and Rationale for the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Trial
Open accessAbstract
Patients with type 2 diabetes mellitus die of cardiovascular disease (CVD) at rates 2-4 times higher than patients without diabetes but with similar demographic characteristics. The prevalence of diabetes is increasing in the United States and, thus, the prevention of CVD in patients with diabetes poses an urgent public health challenge. The objective of this report is to review the current knowledge base for the prevention of CVD in patients with diabetes, with particular emphasis on the control of glycemia, lipids, and blood pressure. Epidemiologic analyses suggest that each 1% increase in glycosylated hemoglobin increases the risk for CVD by approximately 18%; however, evidence from the randomized trials that have examined whether glucose lowering reduces this risk is conflicting. Randomized trials have shown that lowering low-density lipoprotein cholesterol reduces CVD event rates by 17%-43% in patients with diabetes. Limited data support a role for lowering triglycerides and increasing high-density lipoprotein cholesterol in the prevention of CVD. Evidence from clinical trials shows that reducing systolic blood pressure to <140 mm Hg results in 30%-60% reductions in CVD events; however, epidemiologic evidence suggests that lowering to optimal systolic blood pressure levels (<120 mm Hg) may be additionally beneficial. Important questions regarding prevention of CVD in patients with diabetes remain unresolved, including the benefits of near-normal glycemic control, comprehensive therapy for diabetes-related dyslipidemia, and optimal blood pressure control. The Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial will test hypotheses to address these unanswered questions.
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“As hyperglycaemia is linearly associated with increased cardiovascular disease risk 143, 144”
From Type 2 diabetes mellitus and psychological stress — a modifiable risk factor (2017) · cites this paper as [144]
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“When the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study was initiated, however, the available evidence did not clearly support the hypothesis that aggressive lowering of blood glucose concentration in patients with type 2 diabetes would result in cardiovascular benefit.5”
From The association between symptomatic, severe hypoglycaemia and mortality in type 2 diabetes: Retrospective epidemiological analysis of the ACCORD study (2010) · cites this paper as [5]
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“The rationale and study design for the ACCORD trial are described elsewhere.(17,18) Briefly, the ACCORD trial enrolled 10 251 volunteers who had T2DM with a known duration of >3 months, had a glycosylated hemoglobin (HbA1c) of 7.”
MethodGlycemic Control and Cardiovascular Disease: What’s a Doctor to Do?
Kishore, P., Kim, S. H., & Crandall, J. P. (2012) · Current Diabetes Reports · doi:10.1007/s11892-012-0268-5 · Cited by 30
Spagnuolo, C. M., & Hegele, R. A. (2023) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2023.2206015 · Cited by 27
Cardioprotective Properties of HDL: Structural and Functional Considerations
Pappa, E. T., Elisaf, M., Kostara, C. E., Bairaktari, E. T., & Tsimihodimos, V. (2019) · Current Medicinal Chemistry · doi:10.2174/0929867326666190201142321 · Cited by 28
What Is the Role of Advanced Lipoprotein Analysis in Practice?
Robinson, J. G. (2012) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2012.04.067 · Cited by 26
Waly, M. I., Ali, A., Al‐Nassri, A., Mukhaini, M. A., Valliatte, J., & Al-Farsi, Y. M. (2015) · Experimental Biology and Medicine · doi:10.1177/1535370215596860 · Cited by 25
Teaching children with diabetes about adequate dietary choices
Maffeis, C., & Pinelli, L. (2008) · British Journal Of Nutrition · doi:10.1017/s0007114508892495 · Cited by 25
Management of Dyslipidemias in the Presence of the Metabolic Syndrome or Type 2 Diabetes
Matikainen, N., & Taskinen, M. (2012) · Current Cardiology Reports · doi:10.1007/s11886-012-0309-3 · Cited by 24
“These findings reflect the significance of compositional and functional changes in plasma lipoproteins over the fasting plasma lipid concentrations [8, 9].”
BackgroundDoes intensive therapy of type 2 diabetes help or harm? Seeking accord on ACCORD
Hoogwerf, B. J. (2008) · Cleveland Clinic Journal of Medicine · doi:10.3949/ccjm.75.10.729 · Cited by 23
Sridevi, M., Kalaiarasi, P., & Pugalendi, K. V. (2011) · Asian Pacific Journal of Tropical Biomedicine · doi:10.1016/s2221-1691(11)60171-8 · Cited by 24
“elevated triglycerides (TG), low high density lipoprotein cholesterol (HDL-C), and elevated very low density lipoprotein cholesterol (VLDL-C) and low density lipoprotein cholesterol (LDL-C) that increases their risk of cardiovascular disease[3,4].”
BackgroundZhang, Q., Rajagopalan, S. P., Marrett, E., Davies, M. J., Radican, L., & Engel, S. S. (2011) · Diabetes Obesity and Metabolism · doi:10.1111/j.1463-1326.2011.01498.x · Cited by 22
Geulayov, G., Goral, A., Muhsen, K., Lipsitz, J. D., & Gross, R. (2010) · General Hospital Psychiatry · doi:10.1016/j.genhosppsych.2010.09.004 · Cited by 24
“Diabetes is a leading cause of cardiovascular morbidity and mortality and significant contributor to disability in many countries [2].”
BackgroundEskesen, K., Jensen, M. T., Galatius, S., Vestergaard, H., Hildebrandt, P. R., Marott, J. L., & Jensen, J. S. (2012) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2012.02594.x · Cited by 23
Byington, R. P., Bigger, J. T., Buse, J. B., & William, W. (2008) · Cited by 23
Self-citationKhadke, S. P., Mandave, P. C., Kuvalekar, A., Pandit, V. A., Karandikar, M., & Mantri, N. L. (2020) · Nutrients · doi:10.3390/nu12123652 · Cited by 22
“The majority of T2DM individuals failed to achieve all standard goals for lipid management, and, therefore, aggressive management strategies are required to lower lipid abnormalities in T2DM individuals [7,8].”
BackgroundGower, E. W., Lovato, J. F., Ambrosius, W. T., Chew, E. Y., Danis, R. P., Davis, M. D., Goff, D. C., Greven, C. M., Gotto, A. M., Bailey, K. R., et al. (2017) · American Journal of Ophthalmology · doi:10.1016/j.ajo.2017.12.007 · Cited by 22
Self-citationSanches, Í. C., Buzin, M., Conti, F. F., Dias, D. D. S., dos Santos, C. P., Sirvente, R. A., Salemi, V. M. C., Llesuy, S., Irigoyen, M. C., & Angelis, K. D. (2018) · PLoS ONE · doi:10.1371/journal.pone.0202731 · Cited by 22
Linz, P. E., Lovato, L., Byington, R. P., O’Connor, P. J., Leiter, L. A., Weiß, D., Force, R. W., Crouse, J. R., Ismail‐Beigi, F., Simmons, D. L., et al. (2013) · Diabetes Care · doi:10.2337/dc13-0790 · Cited by 21
Self-citationBeeri, M. S., Lin, H., Sano, M. C., Ravona‐Springer, R., Liu, X., Bendlin, B. B., Gleason, C. E., Guerrero‐Berroa, E., Soleimani, L., Launer, L. J., et al. (2018) · JAMA Network Open · doi:10.1001/jamanetworkopen.2018.4458 · Cited by 21
Association of hemoglobin A1c time in range with risk for diabetes complications
Mohr, D. C., Zhang, L., Prentice, J. C., Nelson, R. E., Li, D., Pleasants, E. A., & Conlin, P. R. (2022) · BMJ Open Diabetes Research & Care · doi:10.1136/bmjdrc-2021-002738 · Cited by 22
Triglycerides and coronary heart disease: have recent insights yielded conclusive answers?
Sarwar, N., & Sattar, N. A. (2009) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e32832dd4dc · Cited by 18
Marvel, S. W., Rotroff, D. M., Wagner, M. J., Buse, J. B., Havener, T. M., McLeod, H. L., Motsinger‐Reif, A. A., & The ACCORD/ACCORDion Investigators (2017) · PeerJ · doi:10.7717/peerj.3187 · Cited by 18
“…combined statin-fenofibrate therapy versus strategies with standard targets and approaches in patients with type 2 diabetes at high risk forCVD (Goff et al., 2007; Buse, 2007) The clinical trial was conducted at clinical centers across the United States and Canada, and enrolled 10,251…”
MethodSelf-citationEmerging antidyslipidemic drugs
Pollex, R. L., JOY, T. R., & Hegele, R. A. (2008) · Expert Opinion on Emerging Drugs · doi:10.1517/14728214.13.2.363 · Cited by 19
“Potential beneficial effects of the combination of a statin and fibrate in type 2 diabetes are currently being studied in the ongoing Action to Control Cardiovascular Risk in Diabetes (ACCORD) study [92] .”
BackgroundWest, D. S., Coulon, S. M., Monroe, C. M., & Wilson, D. K. (2016) · American Psychologist · doi:10.1037/a0040394 · Cited by 20
Katula, J. A., Kirk, J. K., Pedley, C. F., Savoca, M. R., Effoe, V. S., Bell, R. A., & Bertoni, A. G. (2017) · Contemporary Clinical Trials · doi:10.1016/j.cct.2016.12.005 · Cited by 17
“These complications can be reduced or delayed by intensive management of glycated hemoglobin (A1C), blood pressure (BP), and lipids [9].”
Zheng, X., Jiang, M., Ren, X., & Han, L. (2022) · Journal of Diabetes and its Complications · doi:10.1016/j.jdiacomp.2022.108360 · Cited by 18
Metadata
- Authors
- Goff, D. C., Gerstein, H. C., Ginsberg, H. N., Cushman, W. C., Margolis, K. L., Byington, R. P., Buse, J. B., Genuth, S., Probstfield, J. L., & Simons-Morton, D. G.
- Affiliations
- Wake Forest University Health Sciences (US)
- Population Health Research Institute (CA)
- Columbia University (US)
- Memphis VA Medical Center (US)
- Hennepin County Medical Center (US)
- University of North Carolina at Chapel Hill (US)
- Case Western Reserve University (US)
- University of Washington Medical Center (US)
- Corresponding author
- Goff, David C.
- ORCID
- Venue
- The American Journal of Cardiology
- Publisher
- Elsevier BV
- Published
- 2007-06
- Volume
- 99
- Issue
- 12
- Pages
- S4-S20
- ISSN
- 0002-9149 (ISSN-L)
- OpenAlex
- W2086199335
- Cited by
- 229
- References
- 136
- Citations by year
- 2025: 8 · 2024: 8 · 2023: 4 · 2022: 6 · 2021: 6 · 2020: 14 · 2019: 11 · 2018: 13 · 2017: 18 · 2016: 14 · 2015: 14 · 2014: 13 · 2013: 10 · 2012: 9
- FWCI
- 14.86
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The American Journal of Cardiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (n01hc95183-23-0-0, n01hc95180-24-0-1, n01hc95184-24-0-1, n01hc95181-23-0-1, n01hc95182-23-0-1, n01hc95178-28-0-1, n01hc95179-25-0-0)
- Centers for Disease Control and Prevention
- National Institute on Aging
- National Heart, Lung, and Blood Institute (N01- HC-95181, N01-HC- 95180, N01-HC-95178, Y1-HC-9035, N01-HC-95184, N01HC95179, IAA #Y1-HC-9035, Y1-HC-1010, N01‐HC‐95183, N01-HC-95182)
- National Eye Institute
- National Institute of Diabetes and Digestive and Kidney Diseases
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Keywords
- type 2 diabetes, cardiovascular disease prevention, cardiovascular risk, glycemic control, HbA1c, LDL cholesterol lowering, triglycerides, HDL cholesterol, blood pressure control, dyslipidemia, ACCORD trial, cardiovascular events
- MeSH terms
- Antihypertensive Agents, Hypolipidemic Agents, Coronary Disease, Diabetes Mellitus, Type 2, Diabetic Angiopathies, Humans, Fenofibrate, Randomized Controlled Trials as Topic, Hydroxymethylglutaryl-CoA Reductase Inhibitors
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