Diabetes Is Potent Predictor of Heart Disease in Women Under 65

Becky McCall

February 02, 2021

Women with diabetes aged between 45 and 65 years have a 10-fold increased risk of coronary heart disease (CHD) compared with those of similar age without diabetes, according to a new analysis of the US-based Women's Health Study.

Identifying individuals at risk of premature CHD — occurring before age 65 years in women or before age 55 years in men — is essential to reducing the burden of premature morbidity and mortality, explain Sagar Dugani, MD, PhD, from the Mayo Clinic, Rochester, Minnesota, and colleagues in their article published online January 20 in JAMA Cardiology.

Although CHD mortality of US adults younger than 55 years declined by 5.5% in men and 4.6% in women from 1979 to 1989, over the subsequent 20 years, mortality for women was virtually unchanged, they note.

"Younger women are an important demographic, and we don't understand why their risk of death is higher," Dugani told Medscape Medical News. "Why don't they show the same improvement as men? Are we missing risk factors? We need these answers to intervene."

As well as diabetes, a new measure reflecting insulin resistance called the lipoprotein insulin resistance (LPIR) score proved to have the highest predictive risk for premature CHD of 50 biomarkers that Dugani and colleagues investigated.

"These data show the importance of diabetes and insulin resistance in younger women, in particular, women under 55, for whom there is very little information," said Dugani.

We assessed [adjusted hazard ratios] for many risk factors, but LPIR score stood out in women under 55 years [and]...was noticeably higher compared to older groups," he added.

Heart Disease Assessed in Four Age Brackets

Dugani and his research team, from Brigham and Women's Hospital, Boston, Massachusetts, investigated the contribution of multiple clinical, lipid, metabolic, and inflammatory risk factors to risk for CHD in women over 45 years of age.

Data on just over 28,000 female health professionals without known cardiovascular disease (CVD) with a median follow-up of 21.4 years were drawn from the Women's Health Study.

Risk factors and 50 biomarkers, including lipids, triglycerides, lipoproteins, inflammatory, and metabolic markers measured at study entry, were assessed for association with CHD onset in four age brackets (< 55, 55 - < 65, 65 - < 75, and ≥ 75 years).

In those under 55 years, the presence of diabetes was associated with a 10-fold increased risk of CHD (adjusted hazard ratio [HR], 10.71); this association was attenuated as women got older, with an aHR of 3.47 in those aged ≥ 75 years.

Other important risk factors for CHD onset in women under 55 years included metabolic syndrome (aHR, 6.09), hypertension (aHR, 4.58), obesity (aHR, 4.33), and smoking (aHR, 3.92).

Dugani stressed, however, that the lower hazard ratios for some risk factors in older age groups "do not suggest that preventive health becomes less important with aging…Management of risk factors is important at all ages."

And some risk factors were important across the age groups, for example, physical inactivity, for which the hazard ratios associated with CHD didn't change significantly as women aged (aHR, 1.53, 1.59, 1.43, 1.21 for < 55, 55 - < 65, 65 - < 75, ≥ 75 years).

Overall, the study reinforces messages about prevention, said Dugani. "It comes down to the four S's lifestyle — sugar, salt, sedentary lifestyle, and smoking," and how best to avoid them.

LPIR Provides "All-Round" Measure, but Not Yet Available in Clinic

The researchers examined 50 or so biomarkers and found the novel LPIR score had the strongest association with risk of CHD in younger women.

LPIR comprises a weighted combination of six lipoprotein measures related to the concentration and size of high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglyceride-rich lipoprotein particles.

Although categorized as a metabolic marker and used in the research setting, it is not yet routinely available in clinics.

"LPIR takes into account other contributory factors (particle size and number) that LDL cholesterol or HDL cholesterol alone do not, so it provides a better all-round measure of the insulin resistance lipoprotein profile," explained Dugani.

These latter traditional biomarkers had much weaker associations with CHD onset in younger women (under 55 years) than LPIR.  

LPIR was associated with a 600% increased risk of CHD in women under 55 years (aHR, 6.4), compared with LDL cholesterol, which was linked to a 40% increase in risk of CHD in this subgroup.

"In comparing risk factors, we were surprised that LPIR stood out to this extent," said Dugani.

Mora has reported receiving institutional research grant support from Atherotech Diagnostics for research outside the current work, serving as a consultant for Quest Diagnostics, and has a patent related to use of GlycA and colorectal cancer risk. The other authors have reported no relevant financial relationships.

JAMA Cardiol. Published online January 20, 2021. Full text

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