medwireNews: An individual patient data meta-analysis confirms that diabetes increases the likelihood for people dying of atherosclerotic disease, with women the worst affected.
In men, having diabetes was associated with a 2.10-fold increased risk for fatal ischemic heart disease, ischemic stroke, or other atherosclerotic disease after accounting for age, BMI, blood pressure, cholesterol levels, and smoking status.
But in women, the risk was increased threefold, report Sarah Lewington (University of Oxford, UK) and colleagues of the Prospective Studies and Asia Pacific Cohort Studies collaborations in The Lancet Diabetes & Endocrinology.
In a linked commentary, Anna Norhammar (Karolinska Institutet, Stockholm, Sweden) stresses that men actually had higher vascular death rates than women; for example, the adjusted rates for people aged 60–69 years were 0.52% versus 0.28% in men and women with diabetes and a corresponding 0.24% and 0.07% in those without.
“[S]ince women without diabetes have the best prognosis, diabetes confers a higher relative risk among women than among men,” she explains.
The researchers found that because men had higher occlusive vascular mortality rates than women overall, the absolute number of events that was directly accounted for by diabetes was similar for men and women. But in men, diabetes accounted for a small proportion of a relatively large number of events, whereas in women it accounted for a larger proportion of a smaller number of events.
The study included 980,793 people (42.0% women), aged between 35 and 89 years. At baseline, 3.4% of women and 5.0% of men had diabetes, and during 9.8 million person–years of follow-up 25.6% of all participants died from occlusive vascular causes, with 91.0% of these deaths being from ischemic heart disease.
The relative effect of diabetes on vascular mortality was most prominent at younger ages, when participants had fewer competing risk factors, but the age difference was only slight in men, whereas in women the risk increase associated with diabetes was 5.55-fold at age 35–59 years, 4.04-fold at age 60–69 years, and 2.40-fold at age 70–89 years.
In her commentary, Norhammar also highlights that traditional risk factors did not explain the increased relative excess risk in women versus men. The strength of the associations of blood pressure, cholesterol levels, and BMI with occlusive vascular mortality was similar in patients with and without diabetes, with no sex differences observed.
This shows “that further research is needed to understand the mechanisms involved and to better target and individualise prevention strategies,” says Norhammar.
She says that in the meantime clinicians should seek to identify high-risk women, and should make patients aware that atypical signs of myocardial ischemia can be similar to those of hypoglycemia. She also calls for in-depth analysis of sex differences in clinical trials and large observational studies, to determine cardiovascular risk profiles and patterns of complications and support individualized treatment.
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