How Cardiovascular Therapies Influence Glucose Metabolism

ACCEL | Despite a decline in cardiovascular disease (CVD) since the 1950s, individuals with diabetes mellitus (DM) still have twice the risk of developing CVD as those without DM and, importantly, the onset of CVD is happening 15 years earlier in people with diabetes. Consequently, the risk of acute myocardial infarction (MI) starts to increase significantly when patients with DM are still in their 40s.1 Moreover, the presence of diabetes has a major influence on coronary heart disease (CHD) risk: lifetime risk of CHD for men is 30% and for women 16%, but in the presence of diabetes, lifetime risk soars to 67% in men and 57% in women. In brief, diabetes confers the highest lifetime risk for CHD than any other single risk factor.2


  • In recent years, new research and updated guidelines have changed some of the standard recommendations for managing cardiovascular risk in patients with diabetes.
  • The presence of diabetes should no longer be considered a coronary heart disease risk equivalent, meaning it is still appropriate to consider preventive therapy in patients with DM.
  • No glucose-lowering medication has yet been shown definitively to reduce the risk of CVD and CVD events in patients with type 2 diabetes.
Having said that, and contrary to previous belief, DM is not a risk equivalent for CHD.3 This is based on a systematic review and meta-analysis of 13 studies involving more than 45,000 individuals followed for up to 25 years (mean = 13.4 years). If a true risk equivalent, people with diabetes but no prior MI should have similar outcomes to patients without DM but a history of MI. Instead, patients with diabetes without prior MI had a 43% lower risk of developing total CHD events compared to patients without diabetes and previous MI.

The take-away message: risk is not set in stone for patients with DM, so preventive CHD therapy is still an option. Also, public health decisions to initiate cardio-protective drugs in patients with diabetes for primary CHD prevention should be based on individual risk assessment and individualized therapy rather than a “blanket” approach of treatment.

Recent research has changed some of the standard recommendations for treating patients with DM, such as the Canadian vascular protection checklist, which traditionally looks like this:

  • A1c: optimal glycemic control (usually ≤7%)
  • Blood pressure: optimal blood pressure control (<130/80 mm Hg)
  • Cholesterol: if there is a decision to treat, Canadian guidelines aim for an LDL <2.0 mmol/l
  • Drugs to protect the heart: ACEI or ARB, statin, aspirin if indicated
  • Exercise: regular physical activity and a healthy diet to achieve and maintain a healthy body weight
  • Smoking cessation

The first issue relating to these recommendations is how often they are not achieved. While the prevalence of meeting those goals has improved in the last 2 decades, NHANES data suggests that only about half of appropriate patients are on statin therapy, for example. For A1c, blood pressure, and target LDL, only 1 in 5 patients meet all three goals.4 Secondly, based on current literature, there are some of nuances that should be recalled when considering checklists like this.

A1c and Glycemic Control

Recent evidence provides the basis for placing a little less emphasis on optimal glycemic control for patients with CHD. The emphasis on glycated hemoglobin or A1c came from data that said, like glucose measurements, the continuum of risk is curvilinear; as A1c rises, the diabetes risk rises disproportionately. The American Diabetes Association recommends lowering A1c to below or around 7%, stating in their 2014 clinical guidelines that this has been shown to reduce microvascular complications of DM and, if implemented soon after the diagnosis of diabetes, is associated with long-term reduction in macrovascular disease.

Cardiologists, however, have found reason for caution after evidence that some new agents to treat diabetes may be associated with increased cardiovascular risk that may wipe out any gains from better glycemic control. Keith A.A. Fox, MD, immediate past-president of ESC, said that based on recent evidence, no one should consider glycated hemoglobin a good biomarker of macrovascular complications. Sanjay Sharma, MD, agreed, noting that good glycemic control benefits microvascular disease but not macrovascular disease. Consequently, he said, “We need to ease off on the ‘sweet spot’ for glycated hemoglobin and focus more on other risk factors for atherosclerosis because in high-risk individuals, there is evidence long-acting insulins have precipitated MI and now the glitazones and gliptins have been associated with heart failure.”

In other words, Dr. Sharma suggests less emphasis on hard and fast targets of glucose and more attention to the metabolic syndrome; this means more global risk reduction as well as pushing harder to get patients to increase activity to improve their metabolic profile. Evidence suggests even a brisk 1-hour weekly walk would be enough to significantly reduce CVD risk as well as all-cause mortality. He said: “For every MET (metabolic equivalent) increase in exercise you reduce your cardiovascular risk by 13%. That makes it more powerful than statins or any other intervention you can name—and it’s free.”

Bottom line: We assumed forever that glucose control was a focus for type 2 diabetes, and that may still be valid for preventing microvascular disease, but we’re much less certain today in terms of the role of glucose control in the prevention of atherosclerotic vascular disease.


  1. Booth GL, Kapral MK, Fung K, Tu JV. Lancet. 2006;368:29-36.
  2. Lloyd-Jones DM, Leip EP, Larson MG, et al. Circulation. 2006;113:791-8.
  3. Bulugahapitiya U, Siyambalapitiya S, Sithole J, Idris I. Diabet Med. 2009;26:142-8.
  4. Stark Casagrande S, Fradkin JE, Saydah SH, et al. Diabetes Care. 2013;36:2271-9.
To listen to an interview with Paul Poirier, MD, about medical therapy for diabetic patients, visit The interview was conducted by Raymond J. Gibbons, MD.

Keywords: CardioSource WorldNews Interventions

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