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Treatment and Prevention of Cardiovascular Disease
 Heart disease is the leading cause of death in the United States, but for patients with diabetes, the concern is even greater to intervene and prevent heart disease before it strikes. Patients with diabetes with no history of cardiovascular disease have as high a risk of a myocardial infarction as the individual without diabetes who has had a cardiac event.[1] Decades ago, the Framingham Study demonstrated that the risk for heart disease and cardiovascular events is two- to three-fold higher among patients with diabetes, as compared with those who do not have the disease.[2] Interestingly, cardiovascular intervention studies like the Scandinavian Simvastatin Survival Study (4S) have demonstrated that patients with diabetes have even a greater risk reduction than nondiabetes patients when lipid-lowering agents with statins are instituted.[3]
Because of this increased cardiovascular risk, it is critical that blood pressure and cholesterol, in addition to glucose, be optimized in the patient with diabetes. The United Kingdom Prospective Diabetes Study (UKPDS) found that LDL cholesterol-lowering was more important a risk factor to modify than blood pressure or blood glucose in reducing the risk for future cardiovascular morbidity and mortality.[4] In addition to lipid lowering, blood pressure control to less than 130/80[5] and aspirin therapy are recommended for prevention of cardiovascular disease in men and women with diabetes who are over age 40; treatment can be initiated at a younger age in people who have cardiovascular disease risk factors.[6]
Cholesterol Guidelines
The American Diabetes Association (ADA) recommends that LDL cholesterol should be less than 100 mg/dL[7,8], though some feel that the goal for LDL should be much lower.[7] The National Cholesterol Education Program's Adult Treatment Panel III (NCEP ATP III) recently recommended that 70 mg/dL is a reasonable therapeutic strategy for patients at very high risk for cardiovascular disease.[9] American diabetes Association treatment recommendations for dyslipidemia are summarized in Table 1.[8] In April of 2004, the American College of Physicians (ACP) published new clinical guidelines for lipid control in the management of type 2 diabetes.[10] The ACP recommended that lipid-lowering therapy should be used for primary prevention of cardiovascular disease among people with diabetes who have never had a cardiovascular event and for secondary prevention among people with known coronary artery disease and type 2 diabetes. Further, once lipid-lowering therapy is initiated, patients with type 2 diabetes should be taking at least moderate doses of a statin and do not typically require routine monitoring of muscle enzymes and liver function.
Table 1. ADA treatment recommendations and goals for cholesterol lowering [8]
- Lifestyle modification focusing on the reduction of saturated fat and cholesterol intake, weight loss, increased physical activity, and smoking cessation has been shown to improve the lipid profile in patients with diabetes.
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- Patients who do not achieve lipid goals with lifestyle modifications require pharmacological therapy.
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- Lower LDL cholesterol to <100 mg/dL (2.6 mmol/L) as the primary goal of therapy for adults.
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- Lowering LDL cholesterol with a statin is associated with a reduction in cardiovascular events.
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- In people with diabetes over the age of 40 years with a total cholesterol >135 mg/dL, statin therapy to achieve an LDL reduction of 30% regardless of baseline LDL levels maybe appropriate.
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- Lower triglycerides to <150 mg/dL (1.7mmol/L), and raise HDL cholesterol to >40 mg/dL (1.15 mmol/L). In women, a HDL goal of 50 mg/dL may be appropriate.
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- Lowering triglycerides and increasing HDL cholesterol with a fibrate is associated with a reduction in cardiovascular events in patients with clinical CVD, low HDL, and near-normal levels of LDL.
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- Combination therapy using statins and fibrates or niacin may be necessary to achieve lipid targets but has not been evaluated in outcomes studies for either event reduction or safety.
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Blood Pressure Guidelines
Based upon a number of studies, a target blood pressure goal of <130/80 mm Hg is recommended for patients with diabetes.5 In the U.K. Prospective Diabetes Study (UKPDS), each 10-mm Hg decrease in mean systolic blood pressure was associated with reductions in risk of 12% for any complication related to diabetes, 15% for deaths related to diabetes, 11% for myocardial infarction, and 13% for microvascular complications. No threshold of risk was observed for any end point.[11]
The Hypertension Optimal Treatment (HOT) trial also found improved outcomes, especially in preventing stroke in patients assigned to lower blood pressure targets. Optimal outcomes in the HOT study were achieved in the group with a target diastolic blood pressure of 80 mmHg (achieved 82.6 mmHg). There is no lower-end threshold value for blood pressure, and many studies have demonstrated that risk continues to decrease well into the normal range.
Table 2. ADA guidelines for hypertension treatment in diabetes[5,8]
- Patients with a systolic blood pressure of 130–139 mmHg or a diastolic blood pressure of 80 mm Hg to 89 mm Hg should be given lifestyle/behavioral therapy alone for a maximum of 3 months and then, if targets are not achieved, should also be treated pharmacologically with agents that block the renin-anglotensin system.
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- Patients with hypertension (systolic blood pressure >140 mm Hg) should receive drug therapy in addition to lifestyle/behavioral therapy.
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- Multiple drug therapy (two or more agents at proper doses) is generally required to achieve blood pressure targets.
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- Initial drug therapy for those with a blood pressure >140/90 should use a drug class demonstrated to reduce CVD events in patients with diabetes (ACE inhibitors, ARBs, β-blockers, diuretics, calcium channel blockers).
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- All patients with diabetes and hypertension should be treated with a regimen that includes either an ACE inhibitor or ARB. If one class is not tolerated, the other should be substituted. If needed to achieve blood pressure targets, a thiazide diuretic should be added.
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- If ACE inhibitors or ARBs are used, monitor renal function and serum potassium levels.
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- There is clinical trial support for each of the following statements:
- In patients with type 1 diabetes with hypertension and any degree of albuminuria, ACE inhibitors have been shown to delay the progression of nephropathy.
- In patients with type 2 diabetes, hypertension, and microalbuminuria, ACE inhibitors and ARBs have been shown to delay the progression to macroalbuminuria.
- In those with type 2 diabetes, hypertension, macroalbuminuria (>300 mg/day), and renal insufficiency, an ARB should be strongly considered.
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Aspirin Therapy
For the past several decades, aspirin via the mechanism of blocking thromboxane synthesis has been used as a primary and secondary strategy to prevent cardiovascular events in nondiabetic and diabetic individuals. Meta-analyses of large-scale trials in men and women with diabetes support the view that low-dose aspirin therapy should be prescribed as a secondary prevention strategy, if no contraindications exist. The current evidence suggests that low-dose aspirin therapy should also be used as a primary prevention strategy in men and women with diabetes who are at high risk (over age 40 or with other CVD risk factors) for cardiovascular events[10,11,12] summary of the American Diabetes Association’s guidelines for aspirin use among people with diabetes appears in Table 3.
Table 3. Aspirin guidelines in patients with diabetes[6,8]
- Use aspirin therapy (75 mg/day to 162 mg/day) as a secondary prevention strategy in diabetic men and women with a history of myocardial infarction, vascular bypass procedure, stroke or transient ischemic attack, peripheral vascular disease, claudication, and/or angina.
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- Use aspirin therapy (75 mg/day to 162 mg/day) as a primary prevention strategy in men and women with type 2 diabetes at increased cardiovascular risk, including those over 40 years of age or who have additional risk factors (family history of CVD, hypertension, smoking, dyslipidemia, albuminuria).
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- Use aspirin therapy as a primary prevention strategy in menand women with type 1 diabetes at increased cardiovascular risk, including those over 40 years of age or who have additional risk factors (family history of CVD, hypertension, smoking, dyslipidemia, albuminuria).
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- People with aspirin allergy, bleeding tendency, anticoagulant therapy, recent gastrointestinal bleeding, and clinically active hepatic disease are not candidates for aspirin therapy. Other antiplatelet agents may be a reasonable alternative for patients with high risk.
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- Aspirin therapy should not be recommended for patients under the age of 21 years because of the increased risk of Reye’s syndrome associated with aspirin use in this population. Generally, aspirin therapy has not been studied in people under the age of 30.
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Conclusions
Prevention of cardiovascular disease among patients with diabetes must be initiated early in the course of disease. In addition to achieving their glycemic goals, patients with diabetes must also control their blood pressure, cholesterol, triglycerides; in patients above the age of 40, unless contraindicated, aspirin therapy should be initiated.
References
- Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laasko M. 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; 339:229-234.
- Kannel WB, McGee DL. Diabetes and cardiovascular disease. The Framingham study. JAMA. 1979; 241:2035-2038.
- Girman CJ, Rhodes T, Mercuri M, et al. The metabolic syndrome and risk of major coronary events in the Scandinavian Simvastatin Survival Study (4S) and the Air Force/Texas Coronary Athersclerosis Prevention Study (AFCAPS/TexCAPS). Am J Cardiol. 2004; 93:136-141.
- Turner RC, Neil HAW, Stratton IM et al. Risk factors for coronary artery disease in non-insulin dependent diabetes mellitus: United Kingdon prospective diabetes study (UKPDS:23). BMJ. 1998; 316:823-828.
- American Diabetes Association. Hypertension management in adults with diabetes. Diabetes Care. 2004;27(suppl 1):S65-S67.
- American Diabetes Association. Aspirin therapy in diabetes. Diabetes Care. 2004; 27(suppl 1):S72-S73.
- American Diabetes Association. Dyslipidemia management in adults with diabetes. Diabetes Care. 2004; 27(suppl 1):S68-S71.
- American Diabetes Association. Standards of medical care in diabetes. Diabetes Care. 2005;28:S4-S36.
- Grundy SM, Cleeman JI, Merz NB, et al. for the Coordinating Committee of the National Cholesterol Education Program. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation. 2004; 110:227-239.
- Snow V, Aronson MD, Hornbake R, et al. Lipid control in the management of type 2 diabetes mellitus: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2004; 140:644-649.
- Adler AI, Stratton IM, Neil HAW, et al for the UK Prospective Diabetes Study Group. Association of systolic blood pressure with macrovascular and microvascular complications of type 2 diabetes. BMJ. 2000; 321:412-419.
- Colwell JA. Aspirin therapy in diabetes. Diabetes Care. 1997; 20:1767–1771.
- Hayden M, Pignone M, Phillips C. Aspirin for the primary prevention of cardiovascular events: a summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med. 2002; 136:161–171.
- US Preventive Services Task Force. Aspirin for the primary prevention of cardiovascular events: recommendation and rationale. Ann Intern Med. 2002; 136:157–160.
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