CVD Risk Similar in Men, Women With Diabetes, but Care Differs

Becky McCall

April 19, 2019

The increased risk of cardiovascular disease (CVD) upon developing type 2 diabetes is similar in men and women, show data from a large UK-based study of newly diagnosed patients.

The new findings contradict prior studies and are the first to show that the proportionate CVD risk increase upon developing type 2 diabetes is similar between the sexes, with a nonsignificant relative risk ratio of 1.07.

However, women are still prescribed fewer therapies than men — including statins and angiotensin-converting-enzyme (ACE) inhibitors — raising concerns that women continue to receive suboptimal disease management.

That observation highlights the need for closer adherence to prescribing guidance, continued routine surveillance for gender-related prescribing biases, and possibly greater uptake of professional-based interventions in the community, note the study authors. The study was published online April 15 in Circulation.

In an interview with Medscape Medical News, senior author Martin Rutter, MD, who is senior lecturer in cardiometabolic medicine at the University of Manchester, England, explained that historical studies show that women have a proportionately greater increase in their CVD risk upon developing diabetes. "Now, in the UK, we've shown that this has been negated, with no statistically significant difference in CVD risk increase between women and men."

Rutter added that the similarity in the degree of CVD risk increase found in men and women might be reflected by the pay-for-performance initiative for general practitioners aimed at improving CVD risk management in type 2 diabetes known as the Quality and Outcomes Framework.

"Managing CVD risk factors and managing diabetes is remunerated in terms of achievement. This system of care might be more equitable for women than historical systems," he said.

However, he stresses that an imbalance in prescribing to counter CVD risk factors remains, with women receiving fewer medications. "Women still appear to be compromised disproportionately."

Vasan Ramachandran, MD, professor of medicine and epidemiology, Boston University School of Medicine and Boston University School of Public Health, and principal investigator of the Framingham Heart Study, commented on the study and its findings.

"It is intriguing that [major adverse cardiovascular event (MACE)] risk is similar in men and women with diabetes mellitus, even though women were less well treated in terms of their other risk factors, and that prior studies reported women had about 25% - 50% higher risk of CVD compared to men," he remarked.

"Despite the lack of sex-related differences in MACE risk, women with diabetes mellitus were more likely to be obese, hypertensive and have hypercholesterolemia, yet less likely to be treated with a statin or blood pressure-lowering medication; women who also had prior CVD were also less likely to be treated with antiplatelet drugs," Ramachandran pointed out.

Data From Nearly 80,000 Cases

CVD risk is increased in all people with type 2 diabetes. While men with the disease have a higher overall risk of CVD than women, prior meta-analyses have shown significant relative risk ratios in women compared with men for fatal coronary heart disease, incident coronary heart disease stroke, and all fatal atherosclerotic disease.

In the current study, Rutter's team analyzed data from 79,985 people diagnosed with type 2 diabetes between 2006 and 2013 (44.3% women), using the Clinical Practice Research Datalink, which is linked to hospital and death records for people in England. They matched these patients with 386,547 adults without diabetes and used sex-stratified Cox models to assess CVD risk.

The primary endpoint was the first record of MACE after the diagnosis of diabetes: myocardial infarction, stroke, and cardiovascular death. Incident type 2 diabetes cases were identified by the first diagnostic code for diabetes recorded between 2006-2013.

Compared with men, women with type 2 diabetes were 2 to 3 years older, had better glycemic control but were more likely to be obese, have hypercholesterolemia and hypertension, and were less likely to be prescribed lipid-lowering medication and/or ACE inhibitors.

During follow-up, MACE occurred in in 9806 people with type 2 diabetes (12.3% overall; 11.6% of women and 12.8% of men) and 30,226 people without diabetes (7.8% overall; 7.4% of women and 8.1% of men).

When cardiovascular event risk was analyzed, compared with women without type 2 diabetes, the study showed that women with type 2 diabetes had a higher cardiovascular event risk (adjusted hazard ratio [HR], 1.20; 95% confidence interval [CI], 1.12 - 1.28). The pattern was similar among men with diabetes vs those without (HR, 1.12; 95% CI, 1.06 - 1.19). This led to a nonsignificant higher relative risk in women (risk ratio, 1.07; 95% CI, 0.98 - 1.17).

Studies Needed in All Ethnicities to Reflect Real-life CVD Risks

Commenting on the study strengths, Ramachandran highlighted the contemporary time period of observation, the very large sample size, the use of an administrative database reflecting people with diabetes in primary care settings, and follow-up of an inception cohort with incident as opposed to prevalent diabetes as studied previously.

However, the results may not apply to all populations, he cautions. "I'm unsure if these findings are generalizable to the US. Similar studies in the US and other countries are warranted. It is especially important to study multi-ethnic samples and evaluate MACE risk in diabetes mellitus by sex within blacks, whites, Hispanics, Asians, and Native Americans, given the differences in diabetes mellitus profile and propensity by race/ethnicity."

He also remarked that it was unclear whether the similarity in CVD risk upon developing type 2 diabetes was maintained beyond the seven-year follow-up. "If women are less well treated, their risk may escalate on longer-term follow-up relative to better-treated men with type 2 diabetes, so a long-term follow-up of this cohort will be interesting, as would a study of other endpoints like chronic kidney disease or retinopathy will be interesting in current sample."

Finally, the reasoning that the reduction in CVD risk differences is due to better management of risk factors in type 2 diabetes also requires replication, he added.

"These new results suggest that the outlook for women with type 2 diabetes is better than previously thought, thanks to improved care," said Elizabeth Robertson, PhD, director of research at Diabetes UK, which funded the study. "However, we need to make sure that everyone with type 2 diabetes gets the best treatments and care, to reduce their risk of life-threatening cardiovascular complications like heart attack or stroke as much as possible," she said in a press release.

Rutter reports receiving research funding from Novo Nordisk, consultancy fees from Novo Nordisk and Roche Diabetes Care, and owning of shares in GlaxoSmithKline, outside the submitted work. Ramachandran has disclosed no relevant financial relationships.

Circulation. Published online April 15, 2019. Abstract

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