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

https://doi.org/10.1016/j.amjcard.2007.03.002Get rights and content

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.

Section snippets

Methods

Pertinent references were identified using Medline database searches of reports related to the prevention of CVD in patients with diabetes. Searches focused on the identification of reports published from January 1990 through January 2003. In addition, more recent reports from major studies and the reference lists of selected reports were reviewed. Pertinent results from randomized controlled trials were synthesized qualitatively.

References (117)

  • L. Hansson et al.

    Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial

    Lancet

    (1998)
  • P.J. Savage

    Cardiovascular complications of diabetes mellituswhat we know and what we need to know about their prevention

    Ann Intern Med

    (1996)
  • J. Stamler et al.

    Diabetes, other risk factors, and 12-yr cardiovascular mortality for men screened in the Multiple Risk Factor Intervention Trial

    Diabetes Care

    (1993)
  • W.B. Kannel et al.

    Diabetes and cardiovascular disease: the Framingham study

    JAMA

    (1979)
  • J.H. Fuller et al.

    Mortality from coronary heart disease and stroke in relation to degree of glycaemia: the Whitehall study

    BMJ

    (1983)
  • E. Barrett-Connor et al.

    Why is diabetes mellitus a stronger risk factor for fatal ischemic heart disease in women than in men?The Rancho Bernardo Study

    JAMA

    (1991)
  • U. Goldbourt et al.

    Factors predictive of long-term coronary heart disease mortality among 10059 male Israeli civil servants and municipal employees: a 23 year mortality follow-up in the Israeli Ischemic Heart Disease Study

    Cardiology

    (1993)
  • J.E. Manson et al.

    A prospective study of maturity-onset diabetes mellitus and risk of coronary heart disease and stroke in women

    Arch Int Med

    (1991)
  • S.M. Haffner et al.

    Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction

    N Engl J Med

    (1998)
  • D.L. Wingard et al.

    Heart disease and diabetes

  • N.J. Morrish et al.

    Incidence of macrovascular disease in diabetes mellitus: the London follow-up to the WHO Multinational Study of Vascular Disease in Diabetics

    Diabetologia

    (1991)

  • Aspirin effects on mortality and morbidity in patients with diabetes mellitusEarly Treatment of Diabetic Retinopathy Study report 14

    JAMA

    (1992)
  • E.M. Damsgaard et al.

    Eight to nine year mortality in known non-insulin dependent diabetes and controls

    Kidney Int

    (1992)
  • A. Neil et al.

    A prospective population-based study of microalbuminuria as a predictor of mortality in NIDDM

    Diabetes Care

    (1993)

  • Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and Micro-HOPE substudy

    Lancet

    (2000)
  • K. Gu et al.

    Diabetes and decline in heart disease mortality in US adults

    JAMA

    (1999)
  • C.S. Fox et al.

    Trends in cardiovascular complications of diabetes

    JAMA

    (2004)
  • G.L. Booth et al.

    Recent trends in cardiovascular complications among men and women with and without diabetes

    Diabetes Care

    (2006)
  • K. Malmberg et al.

    Impact of diabetes on long-term prognosis in patients with unstable angina and non-Q-wave myocardial infarction: results of the OASIS (Organization to Assess Strategies for Ischemic Syndromes) Registry

    Circulation

    (2000)
  • P. Gaede et al.

    Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes

    N Engl J Med

    (2003)
  • S.E. Moss et al.

    The association of glycemia and cause-specific mortality in a diabetic population

    Arch Intern Med

    (1994)
  • J. Kuusisto et al.

    NIDDM and its metabolic control predict coronary heart disease in elderly subjects

    Diabetes

    (1994)
  • D.K.G. Andersson et al.

    Long-term glycemic control relates to mortality in type II diabetes

    Diabetes Care

    (1995)
  • M.-A. Gall et al.

    Albuminuria and poor glycemic control predict mortality in NIDDM

    Diabetes

    (1995)
  • R.C. Turner

    The UK Prospective Diabetes Study: a review

    Diabetes Care

    (1998)
  • M. Wei et al.

    Effects of diabetes and level of glycemia on all-cause and cardiovascular mortality: the San Antonio Heart Study

    Diabetes Care

    (1998)
  • D.R. Hadden et al.

    Macrovascular disease and hyperglycaemia: 10-year survival analysis in type 2 diabetes mellitusThe Belfast Diet Study

    Diabet Med

    (1997)
  • C.C. Fu et al.

    Development of macrovascular diseases in NIDDM patients in northern Taiwan: a 4-yr follow-up study

    Diabetes Care

    (1993)
  • I.M. Stratton et al.

    Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study

    BMJ

    (2000)
  • S. Lehto et al.

    Dyslipidemia and hyperglycemia predict coronary heart disease events in middle-aged patients with NIDDM

    Diabetes

    (1997)
  • H.C. Gerstein et al.

    Cardiovascular diseases

  • E. Selvin et al.

    Meta-analysis: glycosylated hemoglobin and cardiovascular disease in diabetes mellitus

    Ann Intern Med

    (2004)
  • M. Coutinho et al.

    The relationship between glucose and incident cardiovascular events: a metaregression analysis of published data from 20 studies of 95,783 individuals followed for 12.4 years

    Diabetes Care

    (1999)
  • H.C. Gerstein

    Glucose: a continuous risk factor for cardiovascular disease

    Diabet Med

    (1997)
  • B. Balkau et al.

    High blood glucose concentration is a risk factor for mortality in middle-aged nondiabetic men: 20-year follow-up in the Whitehall Study, the Paris Prospective Study, and the Helsinki Policemen Study

    Diabetes Care

    (1998)
  • J.V. Bjornholt et al.

    Fasting blood glucose: an underestimated risk factor for cardiovascular deathResults from a 22-year follow-up of healthy nondiabetic men

    Diabetes Care

    (1999)
  • S.M. Haffner

    The importance of hyperglycemia in the nonfasting state to the development of cardiovascular disease

    Endocr Rev

    (1998)
  • H.C. Gerstein et al.

    Dysglycemia: a key cardiovascular risk factor

    Semin Vasc Med

    (2002)
  • K.T. Khaw et al.

    Association of hemoglobin A1c with cardiovascular disease and mortality in adults: the European Prospective Investigation into Cancer in Norfolk

    Ann Intern Med

    (2004)

  • Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33)

    Lancet

    (1998)

    • Cited by (0)

    This work was supported by Contract Nos. N01-HC-95178, N01-HC-95179, N01-HC-95180, N01-HC-95181, N01-HC-95182, N01-HC-95183, N01-HC-95184, IAA #Y1-HC-9035, and IAA #Y1-HC-1010 from the National Heart, Lung, and Blood Institute (NHLBI), with additional support from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the National Eye Institute (NEI), the National Institute on Aging (NIA), and the Centers for Disease Control and Prevention (CDC). General Clinical Research Centers provide support at many sites.

    †

    A complete list of the members of the ACCORD Study Group is included in the Appendix.

    View full text
    Copyright © 2007 Elsevier Inc. All rights reserved.