Chapter 42

Diabetes and Cardiovascular Disease

Ashish Aneja, MD and Michael E. Farkouh, MD, MSc, FACC

1. What is the current global burden of diabetes, and what is its impact on the epidemiology of cardiovascular disease (CVD)?

    The global burden of diabetes mellitus (DM) in 1985 was an estimated 30 million people. By 2003, it was estimated that there were around 194 million people with diabetes, and this figure is expected to rise to almost 350 million by 2025. At present, the prevalence of DM is much higher in developed countries, but because of urbanization and adoption of western diets and lifestyles, developing countries are rapidly catching up with their developed counterparts. The disease affects a disproportionately higher number of young people in the developing world. The lifetime risk of diabetes is estimated at 32.8% for U.S. males and 38.5% for U.S. females.

    Knowledge of the epidemiology of DM is important to place the expected contribution of DM to the global CVD burden into perspective. The relationship between DM type 1 and type 2 and CVD is well established. In particular, DM is a very strong risk factor for the development of coronary artery disease (CAD) and stroke. The hazard ratio for CAD death in diabetic patients is considered as high as 2.03 (95% confidence interval [CI], 1.60 to 2.59) for men and 2.54 (95% CI, 1.84 to 3.49) for women. Atherosclerosis accounts for 80% of all deaths in diabetic persons, compared with about 30% among nondiabetic persons. Atherosclerotic disease also accounts for greater than 75% of hospitalizations for diabetes-related complications. Patients with diabetes but without previous myocardial infarction (MI) carry the same level of risk for subsequent acute coronary events as nondiabetic patients with previous MI. These results have prompted the Adult Treatment Panel III of the National Cholesterol Education Program to establish diabetes as a CAD risk equivalent, mandating aggressive antiatherosclerotic therapy.

2. What is the impact of diabetes on CVD outcomes?

    In addition to its salutary effects on stable atherosclerotic disease, diabetic patients experience an increased rate of early and late complications following acute coronary syndrome (ACS). Diabetic patients with non–ST segment elevation ACS also experience more in-hospital MIs, associated complications and higher death rates. Diabetic patients also respond less optimally to fibrinolytic therapy, an effect that is sex-dependent—diabetic women fare worse than men. In patients with ACS complicated by hypotension and cardiogenic shock, diabetes is an independent risk variable for adverse outcomes, including death. In the short and long terms, diabetic patients with ACS experience higher rates of heart failure, death, and repeat infarction and require more frequent coronary revascularization.

3. What effect, if any, does diabetes have on the clinical manifestations and prognosis of peripheral arterial disease (PAD) and cerebrovascular disease?

    Diabetes increases the risk of PAD about two- to fourfold. It is more commonly associated with femoral bruits and absent pedal pulses and with a high rate of abnormal ankle-brachial indices, ranging from 11% to 16% in different studies. The duration and severity of diabetes correlates with the incidence and extent of PAD. The pattern of PAD in diabetic patients is characterized by a preponderance of infrapopliteal occlusive disease and vascular calcification. Clinically, PAD in diabetic patients manifests more commonly with claudication and also a higher rate of amputation—the most common cause of nontraumatic amputations.

    Diabetic patients also have a higher rate of intracranial and extracranial cerebrovascular atherosclerosis and calcifications. Patients with a history of stroke have a threefold higher likelihood of being diabetic than do controls, with a risk of stroke that may be up to three- to fourfold higher than that of nondiabetic patients. Compared with nondiabetic subjects, the mortality from stroke in diabetic patients is almost threefold higher. Diabetes also results in a disproportionately higher stroke rate in younger patients and increases the risk of severe carotid disease. In patients younger than 55 years, diabetes increases the risk of stroke about 10 times according to one study. Diabetic patients also suffer worse poststroke outcomes, including a higher mortality rate and recurrence risk and a greater probability of vascular dementia.

4. What is the overall impact of diabetes on the vascular tree?

    Cardiovascular (CV) complications in diabetic patients can be the result of macrovascular disease, including CAD, peripheral arterial disease, and cerebrovascular disease, or can be due to microvascular disease that can result in nephropathy, retinopathy, and neuropathy. Many regard diabetic cardiomyopathy as a distinct entity that is thought to result primarily from hyperglycemia-induced myocardial adverse effects.

5. What is the burden of additional CV risk factors in diabetic patients, and what is their cumulative impact on the atherosclerosis morphology and burden?

    Diabetic patients are known to bear a higher burden of CV risk factors, including twice the prevalence of hypertension, and a higher prevalence of dyslipidemia, including lower high-density lipoprotein (HDL) cholesterol, higher triglycerides, and higher small, dense low-density lipoprotein (LDL) cholesterol levels. The clustering of CV risk factors appears to have a multiplicative effect in diabetic patients, who experience a threefold higher CV mortality than do nondiabetic persons for each risk factor present. In addition, CAD in diabetic patients involves a greater number of coronary vessels and more diffuse atherosclerotic lesions, including significantly more severe proximal and distal CAD.

    Atherosclerotic plaque ulceration and thrombosis also occur more often in diabetic patients. Atherosclerotic plaques in diabetic patients are considered high-risk because of a greater propensity for erosion or rupture, which accounts for a higher incidence of ACS in this population. Diabetic plaques are characterized by high levels of inflammatory cell infiltration, large lipid cores, thin fibrous caps, the presence of new vessel formation (neovascularization) and hemorrhage within the plaque.

6. What characteristics of the atherosclerotic plaque in diabetic patients make it unstable compared with plaque in nondiabetic patients?

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