Spotlight on cardiovascular disease in women with diabetes

Two recent studies looked at cardiovascular disease (CVD) risk in women with type 2 diabetes, finding that fenofibrate may be associated with lowered risk and sulfonylureas with increased risk.

In the first study, published online Aug. 23 by Diabetologia, researchers relooked at the FIELD study which had randomized 9,795 patients with type 2 diabetes, age 50 to 75 years, to 200 mg of fenofibrate or placebo daily for 5 years. The primary end point of the FIELD study, first occurrence of nonfatal myocardial infarction or death from coronary heart disease (CHD), wasn't reduced by fenofibrate. For this analysis the authors focused gender-related differences in fenofibrate response. Fenofibrate did lower total cardiovascular outcomes by 30% in women (P=0.008) and 13% in men (P=0.07), results which didn't differ significantly from one another. Cholesterol levels were reduced for both sexes, but fenofibrate reduced total, LDL and non-HDL cholesterol and apolipoprotein B more for women than men (P<0.001 for all), regardless of menopausal status or statin use, with the most significant gap in LDL (reduced 9.8% for women and 3.3% for men). The differences between women and men on the effect of fenofibrates on lipid and apolipoproteins were “unexpected,” the authors wrote. They noted that while previous studies haven't reported sex differences in response, most of these studies either didn't include women or had a relatively small number of women, especially women with diabetes. While past research has raised some concerns about the safety of fenofibrate for women, these results indicate fenofibrate is “generally safe” for women with type 2 diabetes and is effective for improving an adverse lipoprotein profile and lowering the risk of CVD events, they concluded.

In the other study, published online by Diabetes Care Aug. 22, data on 4,902 women with diabetes from the Nurses' Health Study were used to compare use of sulfonylureas and other diabetes medications to development of CVD. The authors used multivariable Cox proportional hazards models to estimate hazard ratios for sulfonylurea users versus nonusers and then also adjusted for a comprehensive list of potential cofounders. Over a mean of 11 years of follow-up, there were 339 incident cases of CVD, including 191 new cases of CHD and 148 strokes. Compared to those on metformin monotherapy, women who took sulfonylureas and metformin had a relative risk (RR) for CHD of 3.27 (95% CI, 1.31 to 8.17). Longer use of sulfonylureas was associated with higher risk of CHD, with patients who took the drugs for more than 10 years having a RR of 2.15 (95% CI, 1.31 to 3.54) compared to nonusers. The authors did not observe a significant association between sulfonylurea therapy and stroke risk. The study was limited by the possibility of unidentified confounders, confounding by indication, and the lack of differentiation between first- and second-generation sulfonylureas, the study authors noted. They called for prospective cohort studies to replicate the findings.

Also last month, the American Heart Association and American Diabetes Association released a statement ±html about CVD and type 1 diabetes. The statement, published online by Diabetes Care on Aug. 11, addresses differences in cardiovascular pathology between type 1 and type 2 diabetes and discusses cardiovascular screening and treatment options for patients with type 1 diabetes. The statement concludes with a summary of specific areas needing additional research.