U.S. Department of Health and Human Services

Principle 7: Reduce Cardiovascular Disease Risk

Hypertension and dyslipidemia commonly coexist with type 2 diabetes and are clear risk factors for cardiovascular disease (CVD), and diabetes itself confers independent risk. Because of their increased CVD risk, management of hypertension and cholesterol is pa​rticularly important for people with type 2 diabetes. 1 Increased CVD risk also increases the importance of lifestyle modification, including abstinence from smoking. Extensive trial evidence shows the efficacy of targeted treatment of hypertension and statin therapy in the prevention and management of CVD in people with type 2 diabetes.

Although clinical trials to address blood pressure targets and statin therapy have not been conducted in people with type 1 diabetes, attention to CVD risk factors may be particularly important in people with type 1 diabetes because of their high CVD risk.

Evidence for blood pressure control

Although epidemiologic studies suggest that blood pressure higher than 115/75 mmHg is associated with progressive increases in CVD events and mortality in people with diabetes, randomized clinical trials have not demonstrated that lowering blood pressure to less than 140/80 mmHg provides a significant clinical benefit in type 2 diabetes. The United Kingdom Prospective Diabetes Study (UKPDS) found that blood pressure control that targeted less than 150/85 mmHg (achieved 144/82 mmHg) significantly reduced risk for diabetes-related deaths, stroke, heart failure, microvascular disease, retinopathy progression, and deterioration of vision in people with type 2 diabetes compared to a target of 180/105 mmHg. 2  The Hypertension Optimal Treatment (HOT) trial found a 51 percent reduction in major CVD events in people with diabetes at a diastolic goal of 80 mmHg compared with 90 mmHg. 3

The Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial found no substantial advantage in lowering systolic blood pressure to less than 120 mmHg compared to less than 140 mmHg in people with type 2 diabetes, and found a higher risk of serious adverse events with lower blood pressure targets. 4 A meta-analysis of randomized trials in adults with type 2 diabetes found that the use of intensive blood pressure targets (upper limit of 130 mmHg systolic and 80 mmHg diastolic) was associated with a small but significant reduction in stroke but no significant decrease in mortality or myocardial infarction. 5

The Systolic Hypertension in the Elderly Program (SHEP) study found that diuretics reduced CVD death in people with diabetes by 31 percent. 6 Angiotensin converting enzyme (ACE) inhibitors have been shown to provide substantial benefits, including reduced risk of heart attack, stroke, and CVD death 7, 8 and prevention of progression of nephropathy. 9 The Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) study assessed the effects of the routine administration of an ACE inhibitor-diuretic combination in people with diabetes and found a significant reduction in relative risk of major macrovascular or microvascular events, death from CVD, and death from any cause. 10

Blood pressure management

  • Blood pressure should be measured at every routine medical visit.
  • Consider home blood pressure monitoring when office/clinic measurements are borderline or elevated.
  • The following strategies may have antihypertensive effects similar to pharmacologic monotherapy:
    • Reduce sodium intake by selecting low-sodium foods, not adding sodium to food, and limiting processed foods.
    • Reduce excess body weight by increasing consumption of fruits, vegetables, and low-fat dairy products; avoiding excessive alcohol consumption; and increasing activity levels.
    • Follow the Dietary Approaches to Stop Hypertension (DASH) Eating Plan. (See Resources.)
    • Engage in 40 minutes of aerobic physical activity at a moderate to vigorous intensity, at least 3 days a week. 11
  • Referral to a registered dietitian/registered dietitian nutritionist can also be helpful.

Therapy considerations

  • People with a systolic blood pressure of 130 to 139 mmHg or a diastolic blood pressure of 80 to 89 mmHg may initially be treated with lifestyle therapy alone. Overweight people with higher blood pressure should receive both pharmacologic and lifestyle therapy at the time of diagnosis of hypertension.
  • The primary goal of therapy is systolic blood pressure less than 140/90 mmHg. Lower blood pressure targets can be individualized, based upon shared decision making that addresses factors such as the level of CVD risk, presence of kidney disease, and burden of therapy.
  • ACE inhibitors and angiotensin II receptor blockers (ARBs) are contraindicated in pregnancy.

Consider initial therapy with a thiazide, calcium channel blocker, ACE inhibitor, or an ARB. Multi-drug therapy (two or more agents at maximal doses) usually is required to achieve and maintain blood pressure targets. An ACE inhibitor or an ARB reduces progression of chronic kidney disease in people with albuminuria. Individualize further medication choices according to patient characteristics such as age, race, and response to therapy. Measure blood pressure at every health visit and adjust treatment as necessary.

Resources for blood pressure management

Evidence for statin therapy

People with type 2 diabetes commonly have lipid patterns characterized by elevated triglyceride and reduced high-density lipoprotein cholesterol levels. Although their low-density lipoprotein (LDL) cholesterol values are generally not higher than those in non-diabetic individuals, they often have a greater number of smaller, denser, and more atherogenic LDL particles. 12  Studies using the HMG-CoA reductase inhibitors (statins) have clearly shown that moderate to intensive statin therapy can reduce CVD events in people with diabetes. 13, 14, 15, 16 Rather than targeting specific levels of LDL cholesterol, these studies have generally achieved 30 to 40 percent reductions from baseline LDL cholesterol levels. 17  In people with diabetes over age 40 and with other CVD risk factors, moderate- to high-intensity statin therapy reduces CVD risk regardless of the baseline LDL cholesterol level.

Cholesterol management

  • Lifestyle modification to improve lipid profiles is indicated to reduce the risk of CVD in all people with diabetes. This involves actions to reduce intake of saturated fat, trans fat, and cholesterol; to increase intake of omega-3 fatty acids, viscous fiber, and plant stanols/sterols; to increase physical activity; and to reduce weight (if indicated). See Principles 3, 4, and 5 for more information about nutrition and physical activity therapy.
  • Statin therapy should be added to lifestyle therapy, regardless of baseline lipid levels, for people with diabetes who have overt CVD. Statin therapy should be considered in individuals with diabetes who are without overt CVD but are at substantial risk of developing CVD (e.g., over age 40).
  • Risk of CVD is increased more in people with type 1 diabetes compared with type 2 diabetes, but it is not known if routine use of statins in people with type 1 diabetes under age 40 is useful for primary prevention of CVD.
  • The strongest evidence for statin use is in people with diabetes who are 45 to 75 years old. Additional lipid-lowering medications have not been shown to reduce CVD risk in people with type 2 diabetes on statin therapy. 18, 19, 20
  • Statins are contraindicated for women who are pregnant or considering pregnancy. 21

Statin therapy dosage should be carefully titrated according to individual responses to therapy and the occurrence of muscular and other side effects. Measurement of blood lipids may provide information on adherence to therapy. The small increase in the relative risk of developing diabetes with high dose statin therapy is outweighed by the major benefits of statin therapy in reducing CVD and mortality. 22

Resources for cholesterol management

Multiple risk factor reduction

In the Steno-2 Study, 23 a target-driven, long-term, intensified intervention aimed at multiple risk factors in people with type 2 diabetes and microalbuminuria, the risk of cardiovascular and microvascular events was reduced by about 50 percent. This study demonstrated the value of comprehensively addressing CVD risk factors. Long-term follow-up of the participants found significant reductions in CVD deaths. 24

Anti-platelet therapy

Aspirin has been shown to be effective in reducing cardiovascular morbidity and mortality in high-risk people with diabetes and previous myocardial infarction or stroke (secondary prevention). Daily low-dose aspirin therapy (e.g., 75–81 mg) appears to have a modest effect at best on primary CVD prevention in patients with diabetes. In adults with 10-year coronary heart disease (CHD) risk lower than 10 percent (e.g., women under age 60 and men under age 50 without other CVD risk factors), the risk of bleeding may outweigh the atherosclerotic CVD benefits. Studies have not found a clear benefit of low-dose aspirin for primary prevention of atherosclerotic CVD in people without prior disease events. 25, 26, 27

  • Use low-dose aspirin in adults with diabetes and a history of atherosclerotic CVD.
  • In men over 50 and women over 60 with diabetes and other major atherosclerotic CVD risk factors, low-dose aspirin may be considered as a prevention strategy for cardiovascular events. 24
  • For primary prevention of atherosclerotic CVD for people with diabetes, consider aspirin therapy in those who have a 10-year CHD risk of more than 10 percent. 28

Tobacco use cessation

Smoking more than doubles the risk for CVD in people with diabetes. 29 While smokeless tobacco poses a lesser risk for CVD than cigarette smoking, all forms of tobacco should be discouraged. 30 People who stop using tobacco greatly reduce their risk of premature death. Medications, counseling, telephone help lines, and smoking cessation programs increase a person’s chances of success at stopping tobacco use. Additional effective therapies include nicotine replacement products (e.g., gum, inhaler, and patch).

Resources for tobacco use cessation

Note: Failure to take medication regularly as directed should be considered in people who do not meet blood pressure targets or show evidence of cholesterol lowering. Using strategies to help people with diabetes take their medicines as directed can improve adherence and affect their clinical outcomes, productivity, and quality of life. 31

References

1. American Diabetes Association. Standards of medical care in diabetes—2014. Diabetes Care. 2014;37(Suppl 1):S14–80.

2. UK Prospective Diabetes Study (UKPDS) Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ. 1998;317(7160):703–13.

3. Hansson L, Zanchetti A, Carruthers SG, 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. HOT Study Group. Lancet. 1998;351(9118):1755–62.

4. Cushman WC, Evans GW, Byington RP, et al. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med. 2010;362(17):1575–85.

5. McBrien K, Rabi DM, Campbell N, et al. Intensive and standard blood pressure targets in patients with type 2 diabetes mellitus: systematic review and meta-analysis. Arch Intern Med. 2012;172(17):1296–303.

6. Kostis JB, Wilson AC, Freudenberger RS, Cosgrove NM, Pressel SL, Davis BR. Long-term effect of diuretic-based therapy on fatal outcomes in subjects with isolated systolic hypertension with and without diabetes. Am J Cardiol. 2005;95(1):29–35.

7. Heart Outcomes Prevention Evaluation Study Investigators. Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and the MICRO-HOPE substudy. Lancet. 2000;355(9200):253–9.

8. Niskanen L, Hedner T, Hansson L, Lanke J, Niklason A. Reduced cardiovascular morbidity and mortality in hypertensive diabetic patients on first-line therapy with an ACE inhibitor compared with a diuretic/beta-blocker-based treatment regimen: a subanalysis of the Captopril Prevention Project. Diabetes Care. 2001;24(12):2091–6.

9. Nielsen FS, Rossing P, Gall MA, Skott P, Smidt UM, Parving HH. Impact of lisinopril and atenolol on kidney function in hypertensive NIDDM subjects with diabetic nephropathy. Diabetes. 1994;43(9):1108–13.

10. Patel A, MacMahon S, Chalmers J, et al. Effects of a fixed combination of perindopril and indapamide on macrovascular and microvascular outcomes in patients with type 2 diabetes mellitus (the ADVANCE trial): a randomised controlled trial. Lancet. 2007;370(9590):829–40.

11. Eckel RH, Jakicic JM, Ard JD, et al. 2013 AHA/ACC Guideline on lifestyle management to reduce cardiovascular risk: a report of the American College of Cardiology/American Heart Association task force on practice guidelines. Circulation. 2013;129(25 Suppl 2):S76–99.

12. American Diabetes Association. Management of dyslipidemia in adults with diabetes. Diabetes Care. 2000;23(Suppl 1):S57–60.

13. Goldberg RB, Mellies MJ, Sacks FM, et al. Cardiovascular events and their reduction with pravastatin in diabetic and glucose-intolerant myocardial infarction survivors with average cholesterol levels: subgroup analyses in the cholesterol and recurrent events (CARE) trial. Circulation. 1998;98(23):2513–9.

14. Sacks FM, Pfeffer MA, Moye LA, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators. N Engl J Med. 1996;335(14):1001–9.

15. Haffner SM, Alexander CM, Cook TJ, et al. Reduced coronary events in simvastatin-treated patients with coronary heart disease and diabetes or impaired fasting glucose levels: subgroup analyses in the Scandinavian Simvastatin Survival Study. Arch Intern Med. 1999;159(22):2661­7.

16. Colhoun HM, Betteridge DJ, Durrington PN, et al. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet. 2004;364(9435):685–96.

17. Hayward RA, Hofer TP, Vijan S. Narrative review: lack of evidence for recommended low-density lipoprotein treatment targets: a solvable problem. Ann Intern Med. 2006;145(7):520–30.

18. Robins SJ, Collins D, Wittes JT, et al. Relation of gemfibrozil treatment and lipid levels with major coronary events: VA-HIT: a randomized controlled trial. JAMA. 2001;285(12):1585–91.

19. The ACCORD Study Group. Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med. 2010;362(17):1563–74.

20. Boden WE, Probstfield JL, Anderson T, et al. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med. 2011;365(24):2255–67.

21. Kazmin A, Garcia-Bournissen F, Koren G. Risks of statin use during pregnancy: a systematic review. J Obstet Gynaecol Can. 2007;29(11):906–8.

22. Ridker PM, Pradhan A, MacFadyen JG, Libby P, Glynn RJ. Cardiovascular benefits and diabetes risks of statin therapy in primary prevention: an analysis from the JUPITER trial. Lancet. 2012;380(9841):565–71.

23. Gaede P, Vedel P, Larsen N, Jensen GV, Parving HH, Pedersen O. Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N Engl J Med. 2003;348(5):383–93.

24. Gaede P, Lund-Andersen H, Parving HH, Pedersen O. Effect of a multifactorial intervention on mortality in type 2 diabetes. N Engl J Med. 2008;358(6):580–91.

25. Ogawa H, Nakayama M, Morimoto T, et al. Low-dose aspirin for primary prevention of atherosclerotic events in patients with type 2 diabetes: a randomized controlled trial. JAMA. 2008;300(18):2134–41.

26. De Berardis G, Sacco M, Strippoli GF, et al. Aspirin for primary prevention of cardiovascular events in people with diabetes: meta-analysis of randomised controlled trials. BMJ. 2009;339:b4531.

27. Zhang C, Sun A, Zhang P, et al. Aspirin for primary prevention of cardiovascular events in patients with diabetes: A meta-analysis. Diabetes Res Clin Pract. 2010;87(2):211–8.

28. Pignone M, Alberts MJ, Colwell JA, et al. Aspirin for primary prevention of cardiovascular events in people with diabetes: a position statement of the American Diabetes Association, a scientific statement of the American Heart Association, and an expert consensus document of the American College of Cardiology Foundation. Diabetes Care. 2010;33(6):1395–402.

29. Grundy SM, Benjamin IJ, Burke GL, et al. Diabetes and cardiovascular disease: a statement for healthcare professionals from the American Heart Association. Circulation. 1999;100(10):1134–46.

30. Piano MR, Benowitz NL, FitzGerald GA, et al. Impact of smokeless tobacco products on cardiovascular disease: implications for policy, prevention, and treatment—a policy statement from the American Heart Association. Circulation. 2010;122(15):1520–44.

31. Viswanathan M, Golin CE, Jones CD, et al. Interventions to improve adherence to self-administered medications for chronic diseases in the United States: a systematic review. Ann Intern Med. 2012;157(11):785–95.