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Atherosclerotic Cardiovascular Disease Risk (ASCVD) in Diabetes Patients

Treatment of hypoglycemia contributes to ASCVD risk reduction.

Therapies for ASCVD risk factor reduction are directed toward control of dyslipidemia, high blood pressure, glycemic control, and antiplatelet agents. The aim of these treatments is to increase longevity, reduce ASCVD-related events and need for hospitalization as well as improving health-related quality of life. Although older adult patients need these treatments, they should be used with caution due to their adverse effects like myalgias from statin therapy, hypotension, syncope and falls from blood pressure treatments, hypoglycemia from strict blood glucose control as well as risk of bleeding caused by antiplatelet therapy. Their fragile bodies and their short life expectancy confound this problem further.

The American Diabetes Association and American Geriatric Society recommend that relatively healthy older adults with longer life expectancy receive similar ASCVD risk reduction therapies the same as for younger adults. Diet and exercise are an important part of ASCVD risk reduction in both older and younger patients. In the Diabetes Prevention Program study, patients above 60 years of age had greater risk reduction for progressing to type 2 diabetes with diet and exercise compared with younger patients or patients on metformin. In the Look AHEAD study, older patients on diet and exercise treatment had greater improvements in physical function than younger subjects. Older adults at risk of undernutrition and obesity can benefit from nutritional counseling. For older adults with diabetes, reduction of sedentary time will include chair exercises, walking in place, or performing arm and leg lifts. Some of the patients above 65 have frail bodies and complex health, and these exercises can be safely and effectively used with good adherence.

ADA guidelines recommend moderate-intensity statins for treatment of dyslipidemia for patients with diabetes aged 65-75 years without ASCVD and high-intensity statins for patients with ASCVD. Those age ≥75 years with or without ASCVD should receive moderate-intensity statins as it is presumed they would be unable to tolerate higher dosages. Non-statins lipid lowering agents are not recommended in this patient population.

According to ADA, AGS, and JNC8, blood pressure goals should be tailored around individual patient characteristics to minimize risk of harm. Studies have shown that focusing on diastolic blood pressure control can result in harm in older adult patients. Due to advanced age, frail bodies and complex health, aggressive blood pressure control is not recommended. In the SPRINT trial, aggressive BP treatment to bring patients to goal lead to reduction in ASCVD and mortality, but these benefits were counterbalanced by a sharp increase in serious adverse events such as hypotension, dizziness, falls, electrolyte imbalance, and acute kidney injury. This would be a perilous route to take for older patients with diabetes.

The AGS recommends aspirin 75-325 mg a day only for older adults with known CVD unless contraindicated. In a Japanese study on individuals with diabetes but no ASCVD, benefit of aspirin use on ASCVD events was shown among subjects age ≥65 years (6.3% vs. 9.2%, P = 0.047) but not <65 years. However, this treatment led to Serious GI bleeds. Low dose aspirin showed no benefits in older adults at high risk of ASCVD some of whom had diabetes.

Diabetes patients who are above 65 years of age are very vulnerable to hypoglycemia due to impairment of their counterregulatory mechanisms that prevent detection and recovery from hypoglycemia. In the ACCORD trial, hypoglycemia was associated with increase in mortality with standard therapy while in ADVANCE trial, severe hypoglycemia lead to an increased incidence in micro and macrovascular events and ASCVD-related mortality. Therefore, minimizing hypoglycemia risk in older diabetes patients is important and can be achieved through patient education and use of therapies that have low risk for hypoglycemia.

In conclusion, additional research on risk-to-benefit ratio of treatments used in older adults keeping in mind their overall health status is needed. Hypoglycemia is a major contributor to ASCVD risk and diabetes medications should be used with caution in this vulnerable population, particularly in those with compromised renal function.

Practice Pearls:

  • Therapies for ASCVD risk factor reduction are directed toward control of dyslipidemia, high blood pressure, blood glucose as well as antiplatelet agents.
  • Blood pressure goals should be tailored around individual patient characteristics to minimize risk of harm.
  • Moderate-intensity statins are recommended for treatment of dyslipidemia in patients with diabetes aged 65-75 years without ASCVD and high-intensity statins in patients with ASCVD.
  • Hypoglycemia is a major contributor to ASCVD risk and diabetes medications should be used with caution and renal function monitored closely.

References:

Korytkowski MT. Forman DE.  Management of atherosclerotic cardiovascular disease risk factors in the older adult patient with diabetes. Diabetes Care 2017; 40:476–484

Ogawa H. Nakayama M. Morimoto T, et al.; Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes (JPAD) Trial Investigators. Low-dose aspirin for primary prevention of atherosclerotic events in patients with type 2 diabetes: a randomized controlled trial. JAMA 2008; 300:2134–2141pmid:18997198

 

Josephat Macharia, PharmD candidate, Lecom School of Pharmacy class of 2018