Interventions for Cardiovascular Risk Reduction in Type 2 Diabetes Must Be Multifactorial

Heart disease the leading cause of death in diabetic patients
Value-Based Care in Cardiometabolic Health Dec 2012, Vol 1, No 3 - Cardiometabolic Health
Wayne Kuznar

Boston, MA—Optimal cardiovascular (CV) risk reduction in patients with diabetes must be multifactorial, stated James R. Gavin III, MD, PhD, Clinical Professor of Medicine, Emory University, Atlanta, GA, at the 2012 Cardio­metabolic Health Congress.

A great deal is known about CV disease (CVD) in diabetes, yet its prevention remains a paradox. No matter how well its risks are mitigated, the rates of CVD in the presence of diabetes remain higher than in its absence “in ways that simply make no sense,” Dr Gavin said.

Coronary heart disease (CHD) is the leading cause of death in patients with diabetes. Although there are a host of emerging risk factors for CHD that ultimately lead to atherosclerosis and vulnerable plaque, 9 modifiable risk factors account for 90% of the risk for myocardial infarction (MI) worldwide, said Dr Gavin.

Multifactorial Risk Factors
As demonstrated in the Interheart study, these 9 risk factors are dyslip­idemia, smoking, hypertension, diabetes, abdominal obesity, psychosocial factors, a low consumption of fruits and vegetables, excessive alcohol intake, and being inactive.
Therefore, for optimal CV risk reduction, interventions must be multifactorial, he argued.

“The greater the number of traditional risk factors, the greater the incidence of events, including definitive events [ie, death],” Dr Gavin noted. In patients with diabetes, the age-adjusted rate of CHD-related death increases from approximately 35 per 10,000 person-years with no CHD risk factors to >120 per 10,000 person-years with 3 risk factors. The corresponding rate in those without diabetes is ≤33%.

Therefore, another nagging paradox is that in the absence of additional discernible risk factors, diabetes alone is associated with increased rates of CVD events compared with CVD event rate in the absence of diabetes, Dr Gavin noted.

The multifactorial approach to preventing vascular disease in diabetes should include lifestyle intervention, glucose lowering, lipid modification, and blood pressure (BP) lowering.

Lifestyle Changes Are Key
Lifestyle changes have been shown to reduce the need for pharmacologic therapy, he said. Among patients with impaired glucose tolerance, fewer of those who were assigned to weight reduction and moderate-intensity physical activity for at least 150 minutes weekly required antihypertensive drug therapy and lipid-modifying drug therapy than those assigned to metformin or to placebo.

Exercise has been shown to reduce the risk of all-cause death and CV death among patients with diabetes, regardless of whether they are normotensive or hypertensive.

Dietary intervention has also reduced the rate of mortality in many primary prevention trials by reducing the rate of CVD events.

Despite the demonstrated benefits of lifestyle intervention, it is “not taken seriously enough or pursued consistently or intensively enough to reduce vascular disease or provide CVD risk reduction in persons with diabetes,” Dr Gavin pointed out. “Despite this limitation, it is an essential platform upon which all other treatment interventions must be built, for any treatment to be successful.”

Beyond lifestyle interventions, early and comprehensive reduction of risk factors is needed to prevent vascular disease in diabetes, he said.

Early Glycemic Control
The contribution of hyperglycemia to CVD in patients with type 2 diabetes was explored in the United Kingdom Prospective Diabetes Study (UKPDS) and offers “a compelling argument for early glucose control,” said Dr Gavin. The UKPDS researchers uncovered a legacy effect of early glucose control on any macrovascular disease; 8.5 years after the trial was completed, patients who had early intensive glycemic control suffered 15% fewer MIs and had a 13% reduction in all-cause mortality compared with those patients assigned to less-intensive control.

In the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, a target hemoglobin (Hb) A1c level of <7% was associated with a significant reduction in the risk of nonfatal MI but a significant increase in CV death. There was no significant effect of achieving an HbA1c <7% on these end points in the Action in Diabetes and Vascular Disease trial and in the Veterans Affairs Diabetes Trial. The message is that an individualized, patient-centered approach is needed to achieve glycemic control, with looser targets for those with advanced CVD, Dr Gavin acknowledged.

Lipid Lowering
Lipid lowering with atorvastatin did reduce the risk of a first CV event, including stroke, in patients with type 2 diabetes in the Collaborative Atorva­statin Diabetes Study (CARDS). The number needed to treat to prevent 1 event was only 27, demonstrating the importance of lipid lowering in the prevention of CVD in patients with type 2 diabetes.

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