Lowering Cardiovascular Disease Risk for Patients With Diabetes

BACKGROUND

Pharmacists are in the unique position to not only educate patients about diabetes but also discuss the preventable complications that can stem from diabetes. Specifically, pharmacists can help to address risk factors that contribute to cardiovascular disease, such as hypertension, lipid levels, and antiplatelet agents and offer lifestyle modifications when reviewing medications and counseling their patients about this chronic health disease.

The CDC 2017 National Diabetes Statistics Report estimated that over 30 million individuals, or 9.4% of the US population, have diabetes.¹ Of these 30 million people, about 25% do not have a diabetes diagnosis.¹ In 2015, diabetes was the seventh leading cause of death, with heart disease as the leading cause.² The contributing factors to these statistics include the complications that accompany diabetes, such as heart disease and stroke; eye problems that can lead to blindness; and kidney disease and amputations. There is a strong correlation between diabetes and cardiovascular disease (CVD), which is the leading cause of death in patients with diabetes.³ In fact, at least 68% of adults >65 years with diabetes die from some form of heart disease, and adults with diabetes are 2 to 4 times more likely to die from heart disease than adults without the condition (figure 1⁴).^5,6

Pharmacists should ensure that patients have access to all the resources needed to control blood glucose and glycated hemoglobin and should edu- cate patients to ensure they take the steps necessary to minimize risks for complications. Even when glucose is controlled, patients with diabetes have an increased risk of heart disease and stroke, as there are often other risk factors present that contribute to CVD, such as hypertension, dyslipidemia, obesity, tobacco use, and physical inactivity.¹

Hypertension

Hypertension is associated with insulin resistance and is a major risk factor for both atherosclerotic CVD (ASCVD) and microvascular complications

of diabetes.^3,5 Adjusted for age, the prevalence of hypertension in the United States is 57.3% in adults with diabetes compared with 28.6% in those without. Higher rates may be seen in older adults (figure 2⁸).⁷ In type 1 diabetes, hypertension often results from diabetic kidney disease. In type 2 diabetes, it often presents with other risk factors such as using tobacco, being overweight or obese, and living a sedentary lifestyle.^3,9

Based on data from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) and Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) blood pressure (BP) trials, the American Diabetes Association (ADA) recommends that BP be measured at every visit; elevated readings should be confirmed at a separate visit.₃

In patients with BP >140/90 mm Hg, pharmacologic therapy and lifestyle interventions should be initiated promptly.3 Per the ADA and the Eighth Joint National Committee, patients with diabetes and hypertension should be treated for a goal of <140/90 mm Hg; lower targets (eg, <130/80 mm Hg) may be considered for patients with a high CVD risk if they can be achieved without increased burden on the patient._^3,7 An angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) is recommended as first-line treat- ment, and if one class is not tolerated, the other class should be initiated.3 Other options include thiazide-like diuretics or dihydropyridine calci- um channel blockers. Multiple drug therapies are often required to achieve BP targets.3 For patients with confirmed BP >160/100 mm Hg, a new rec- ommendation by the ADA in 2017 states that in addition to lifestyle modifications, patients should have prompt initiation of 2 drugs (separate or in a combination formulation) to reduce cardiovascular events.3 The American Association of Clinical Endocrinologists (AACE) and American College of Endocrinology (ACE) guidelines recommend a BP goal of <130/80 mm Hg and an ACE inhibitor or ARB—or an ACE inhibitor/ARB plus a calcium channel blocker, a beta-blocker, or a thiazide diuretic&mdash;if initial BP is >150/100 mm Hg.¹⁰

LIPID MANAGEMENT

Statins, or 3-hydroxy-3-methylglu- taryl-coenzyme reductase inhibitors, have been shown to reduce ASCVD event rates in diabetes, with some of the benefit being attributed to their anti-inflammatory effects.7 When low-density lipoprotein (LDL) cholesterol is reduced by just 39 mg/dL (1 mmol/L), mortality in high-risk individuals is reduced by 19% and major vascular events are reduced by 21% in patients, regardless of risk factors.⁷ ASCVD risk factors include LDL cho- lesterol >100 mg/dL, high BP, smoking, chronic kidney disease, albuminuria, and a family history of premature ASCVD.³

The AACE/ACE guidelines recommend treatment with a moderate-intensity statin for patients with diabetes between the ages of 40 and 75 and a high-intensity statin for ages 40 to 75 years with a >7.5%10-year risk of cardiovascular disease.¹¹

In those <40 or >75 years, statin therapy should be individualized based on the benefits of ASCVD risk reduction versus potential adverse effects, drug interactions, and patient preference.¹¹ For patients >75 years, moderate-intensity therapy is recommended for those with or without ASCVD, as higher dosages are expected to be less tolerable. These recommendations are consistent with ADA rec- ommendations, with the added caveat that decisions for intensity of therapy be based on health status rather than age alone.¹²

AACE/ACE guidelines stratify 3 risk levels of patients: high (diabetes but no other major risk and/or age <40), very high (diabetes + major ASCVD risk factors), and extreme (diabetes + established clinical CVD).10 These guidelines recommend treat- ment of dyslipidemia with statins to desirable levels of LDL cho- lesterol <100 mg/dL for high, <70 mg/dL for very high, and <55 mg/dL for extreme risk levels. Desirable levels of non—high-density lipoprotein (HDL) cholesterol are <130 mg/dL for high risk, <100 mg/dL for very high risk, and <80 mg/dL for extreme risk levels. The desirable level for triglycerides is <150 mg/dL for all risk levels.¹⁰

ANTIPLATELET AGENTS

Platelet activation and atherothrombosis play key roles in heart attacks, strokes, and the formation and progression of athero- sclerotic plaques^.7 Aspirin has been shown to be beneficial as secondary prevention in reducing cardiovascular morbidity and mortality in high-risk patients with previous myocardial infarction or stroke.3 In these high-risk patients, aspirin was associated with a 27% odds reduction in major adverse cardiovascular events but only a 10% reduction in low-risk patients for primary prevention, which was nonsignificant.7 The net benefit of aspirin use for primary prevention in patients with no previous cardiovascular event remains controversial. ³

The 2016 ADA recommendations regarding aspirin therapy are consistent with the AHA/ACC’s statement on aspirin for primary prevention in patients with diabetes.7 Aspirin should be considered for primary prevention in patients with diabetes who are at increased cardiovascular risk, including most men and women >50 years with at least 1 major risk factor who are not at increased risk of bleeding^.3 As dosages in clinical trials in patients with diabetes varied, there is lacking evidence to support any specific dose. The ADA recommends using dosages 75 to 162 mg/day but notes using the lowest-possible dose may help reduce adverse effects. For patients with ASCVD and documented aspi- rin allergy, clopidogrel (75 mg/day) should be used. Aspirin in combination with clopidogrel is reasonable for up to a year after an acute coronary syndrome^.3

Aspirin is not recommended for patients with diabetes at low risk of ASCVD (<50 years with no other major ASCVD risk fac- tors; 10-year ASCVD risk <5%), as risks of significant bleeding outweigh the benefit.³ Aspirin use is contraindicated in patients <21 years because of the risk of Reye syndrome.³

LIFESTYLE INTERVENTIONS

In addition to interventions to ensure that patients receive proper hypertension, dyslipidemia, and antiplatelet agents, pharmacists should also recommend lifestyle interventions for all patients with diabetes who are at risk for ASCVD and those with known ASCVD.3,7 Over 87% of adults with diabetes in the United States between 2011 and 2014 were overweight or obese (body mass index >25 kg/m2), with 43.5% of those having obesity and 17.8% having severe obesity. Also, 40.8% of these patients were physically inactive, 15.9% were current smokers, and 34.5% had a history of smoking.1 These are modifiable risk factors that pharmacists can affect when counseling patients.

Physical activity should be recommended to all patients, as physical inactivity is associated with increased risk of mortality^.7 Even occasional physical activity (< once/week) reduces the risk of all-cause mortality by 28%, and exercising once weekly reduces risk of mortality by 40% compared with a completely sedentary lifestyle.⁷

Weight loss, for overweight or obese patients, is one of the major lifestyle modifications for the prevention and management of ASCVD.³ Weight loss increases HDL cholesterol, decreases triglycerides, and decreases blood pressure. Even weight loss of 5% to 7% of body weight is beneficial and is recommended for those who are overweight or obese.⁶ Strategies for weight loss in diabetes include^:7

• Following a Mediterranean diet
• Following an intensive program combining diet and physical
• activity
• Self-weighing on a weekly basis
• Eating breakfast regularly
• Increasing physical activity
• Decreasing portion sizes
• Replacing meals

Patients should reduce their intake of saturated fat, trans fat, and cholesterol and increase their intake of dietary fiber, omega-3 fatty acids, fiber, and plant sterols and stanols.³ Pharmacists may refer to the dietary approaches to stop hypertension (DASH) diet, the ADA recommendations for medical nutritiontherapy,and the AHA/ACC lifestyle management guidelines for further information regarding dietary recommendations.

Finally, all patients should be routinely asked about tobacco use. Tobacco users should be recommended for pharmacologic therapy and referred to educational and support programs to assist with tobacco cessation.

CONCLUSION

Although there are many ways a patient can reduce the risk for diabetes or complications from diabetes, pharmacists have intimate knowledge of a patient’s health and a holistic perspec- tive to guide them toward healthier outcomes. It is because of this position that pharmacists can make lasting impacts on their patient’s well-being with simple review, education, and coun- seling of what they see from a health provider’s perspective and how the patient can set the foundation for their short- and long-term health goals.

JEFFREY HAMPER, PHARMD, BCACP, is manager of academic relations at Albertsons Companies in Boise, Idaho, and an affiliate faculty member at Idaho State University, Pocatello, Idaho.

REFERENCES

1. National Diabetes Statistics Report, 2017. CDC website. cdc.gov/diabetes/ pdfs/data/statistics/national-diabetes-statistics-report.pdf. Accessed July 12, 2017. 2. Health, United States, 2016: with chartbook on long-term trends in health. Hyattsville, MD. 2017. CDC website. cdc.gov/nchs/data/hus/hus16.pdf. Accessed August 13, 2017.

3. American Diabetes Association. Cardiovascular disease and risk management. Diabetes Care. 2017;40(suppl 1):S75-S87. doi: 10.2337/dc17-S012.

4. Rosenquist KJ, MD, and Caroline S. Fox CS. Mortality trends in type 2 diabetes. National Institute of Diabetes and Digestive and Kidney Diseases web- site. niddk.nih.gov/about-niddk/strategic-plans-reports/Documents/Diabetes%20 in%20America%203rd%20Edition/DIA_Ch36.pdf. Published December 2016. Accessed August 29, 2017.

5. Cardiovascular disease & diabetes. American Heart Association website. heart. org/HEARTORG/Conditions/More/Diabetes/WhyDiabetesMatters/Cardiovas- cular-Disease-Diabetes_UCM_313865_Article.jsp/#.WXExk8aWyUk. Updated April 14, 2017. Accessed August 13, 2017.

6. Prevent complications. CDC website. cdc.gov/diabetes/managing/problems. html. Updated September 27, 2016. Accessed July 12, 2017.

7. Low Wang CC, Hess CN, Hiatt WR, Goldfine AB. Clinical update: cardio- vascular disease in diabetes mellitus. Atherosclerotic cardiovascular disease and heart failure in type 2 diabetes mellitus—mechanisms, management, and clinical considerations. Circulation. 2016;133(24):2459-2502. doi: 10.1161/CIRCULA- TIONAHA.116.022194.

8. Barrett-Connor E, Wingard D, Wong N, Goldberg R. Heart disease and diabetes. National Institute of Diabetes and Digestive and Kidney Diseases web- site. niddk.nih.gov/about-niddk/strategic-plans-reports/Documents/Diabetes%20 in%20America%203rd%20Edition/DIA_Ch18.pdf. Accessed August 29, 2017. 9. Ganda OP. Diabetes and heart disease—an intimate connection. Joslin Diabetes Center website. joslin.org/info/diabetes_and_heart_disease_an_intimate_connec- tion.html. Accessed July 12, 2017.

10. Garber AJ, Abrahamson MJ, Barzilay JI, et al. Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the comprehensive type 2 diabetes management algorithm—2017 executive summary. Endocr Pract. 2017;23(2):207-238. doi: 10.4158/EP161682.CS.

11. Stone NJ, Robinson JG, Lichtenstein AH, et al; American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2013 ACC/ AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines [erratum in J Am Coll Cardiol. 2015;66(24):2812] [erratum in J Am Coll Cardiol. 2014;63(25 Pt B):3024-3025]. J Am Coll Cardiol. 2014;63(25 Pt B):2889-2934. doi: 10.1016/j. jacc.2013.11.002.

12. Korytkowski MT, Forman DE. Management of atherosclerotic cardiovascular disease risk factors in the older adult patient with diabetes. Diabetes Care. 2017;40(4):476-484. doi: 10.2337/dc16-0815.