Higher HDL Lowers CVD Risk in Type 2 Diabetes

Every 5 mg/dL increase in baseline HDL was associated with a 6% reduction in the CVD hospitalization risk. During a mean follow-up of 55.8 months, each 5 mg/dL increase in HDL was associated with a 4% lower risk.

A categorical analysis centered on a baseline HDL showed that a ≥6.5 mg/dL decrease was associated with an 11% increase in CVD risk, whereas a ≥6.5 mg/dL increase reduced the CVD hazard by 8%, as compared with individuals who remained within 6.4 mg/dL of baseline values.

Gregory A. Nichols, PhD, of Kaiser Permanente Center for Health Research in Portland, Oregon wrote, "Our results add to the growing body of evidence that increasing the HDL cholesterol levels might be an important strategy for CVD risk reduction." "The prevention of HDL cholesterol decreases could be equally important."

Patients with type 2 diabetes have a substantially elevated risk of CVD, with estimates ranging as high as 87% greater compared with nondiabetic adults. Reduction of LDL cholesterol remains the focus of lipid management to reduce CVD risk. However, clinical trials of intensive LDL-lowering with statin drugs have shown that at least 10% of patients have major CVD events.

Glycemic control remains the focus of diabetes management, although intensive hypoglycemic treatment has failed to reduce CVD risk in type 2 diabetics, they continued. The findings suggest that treatment targets other than LDL and hemoglobin A1c deserve consideration.

HDL cholesterol offers one potential target for CVD risk reduction in patients with type 2 diabetes. About half of diabetic patients have low HDL levels, an observation that has generated speculation that raising HDL levels might substantially reduce CVD risk in that patient population.

Clinical studies have yet to produce clear evidence that increasing HDL levels will reduce CVD risk in type 2 diabetes, possibly because of the lack of safe and effective agents, the authors continued. Attempts to use drugs to raise HDL have generally been unsuccessful. Several trials of HDL-raising drugs have been stopped because of an increase in cardiovascular events and mortality.

The search continues, however, for a safe HDL-raising drug. And current studies have shown good results for anacetrapib in terms of safety and efficacy.

In an effort to inform on the association between HDL level and CVD risk in type 2 diabetes, they performed a retrospective cohort study of 30,067 members of the Kaiser Permanente Northwest and Georgia regions. All patients had type 2 diabetes and had at least two HDL cholesterol measurements during 2001 to 2006. Investigators analyzed clinical data on the patients through 2009 to determine whether change in HDL cholesterol influenced subsequent risk of CVD-related hospitalization. They examined HDL cholesterol continuously and by three categories: HDL increase ≥6.5 mg/dL from baseline, decrease ≥6.5 mg/dL, and no increase or decrease >6.4 mg/dL.

During follow-up, 61% of the patients had HDL levels that remained within 6.4 mg/dL of baseline values, 21.6% had ≥6.5 mg/dL increases in HDL, and 17% had ≥6.5 mg/dL decreases.

The authors found that 3,023 (10.1%) patients had CVD-related hospitalizations during the follow-up period. After multivariate adjustment, they found that every 5 mg/dL greater baseline HDL level was associated with a statistically significant 6% reduction in the hazard for CVD hospitalization (P<0.0001), and each 5 mg/dL increase from baseline was associated with a 4% reduction in CVD risk (P<0.003).

The categorical analysis showed that every 6.5 mg/dL increase in HDL during follow-up was associated with an 8% reduction in CVD risk, which did not achieve statistical significance (P=0.077). However, each 6.5% or greater decrease in HDL was associated with a significant 11% increase in the CVD hospitalization hazard (P=0.047).

Acknowledging the study's limitations, the authors wrote that an observational study cannot prove causality. They also noted that they could not determine the reasons for changes in HDL levels or whether the changes were maintained throughout the follow-up period. In addition, 24% of patients with type 2 diabetes could not be included in the study because they did not have two HDL measurements. "Despite these limitations, we have concluded that the changes in HDL cholesterol are associated with changes in the risk of CVD hospitalizations," the authors wrote in conclusion. "Additional study is needed to understand the role of improving HDL cholesterol in a multifactorial prevention strategy."

Practice Pearls:

• Explain that a study found that patients with type 2 diabetes who had higher baseline HDL levels or increased HDL from baseline by whatever means had a lower risk of hospitalization for cardiovascular disease than those with lower HDL levels.

• Note that while an observational study cannot prove causality, type 2 diabetics whose HDL decreased by ≥6.5 mg/dL showed a significantly increased risk of hospitalization for cardiovascular disease.