Relationship Between Cardiac Issues, Diabetes Gets Plenty of Attention

From a session called “How to Navigate the Maze of Pharmacotherapy in Diabetes?” to oral abstracts and posters, the relationship between cardiac risks and rising incidence of type 2 diabetes mellitus (T2DM) received plenty of attention Saturday at the 63rd Scientific Sessions of the American College of Cardiology, being held in Washington, DC.

Diabetes now affects nearly 26 million Americans, and an estimated 35% of US adults over age 20 have prediabetes.¹ Most of the increase has come from the rise in adults and even children with T2DM; 3600 children are diagnosed each year.¹

Treating diabetes has proved tricky because for many years therapies were developed with a blind spot for their cardiovascular (CV) effects; with the well-documented uproar over rosiglitazone (Avandia) in the middle of the past decade,² the posture of the US Food and Drug Administration (FDA) has shifted to require evaluation of CV risk for diabetes therapies.

Options for diabetes drugs abound today; Silvio E. Inzucchi, MD, of Yale School of Medicine, noted during the pharmacotherapy session that decades ago, hypertension had multiple treatement options while diabetes had comparatively few; now the situation is reversed. And yet, he said, drug development will continue because the “holy grail,” a diabetes therapy that has no side effects and the benefit of CV risk reduction, “is something that has eluded us for many years.”

Part of treatment means understanding that men and women present disease differently. And those differences were the focus of several presentations at a poster session Saturday morning, as the theme continued to be moving away from “one size fits all” in understanding the relationship between cardiac and diabetes care. Among the results presented Saturday:

Gender differences in predicting CAD.³ A study from Japan involved 813 male and 413 female subjects who underwent their first coronary angiography and had A1C levels measured from December 2008 to September 2013. Researchers measured coronary artery lesions using the SYNTAX score, a classification developed from existing measurements to classify coronary artery disease (CAD). A logistic regression analysis evaluated predictors for CAD prevalence, adjusting for age, level of hypertension, dyslipidemia, smoking, diabetes, and glycated hemoglobin (A1C).

Among men, A1C was the independent predictor of CAD, but among women, adjusting for diabetes eliminated the predictive value of A1C for CAD. Among men, A1C value showed a significant correlation with SYNTAX score, but there was not a significant correlation between A1C and SYNTAX score among women.

Gender, A1C, and coronary atherosclerosis. A study from Austria enrolled 1449 patients—484 women and 965 men—who did not have previously known diabetes and who underwent coronary angiography for the evaluation of stable CAD. Significant coronary atherosclerosis was diagnosed in the presence of significant coronary stenosis with lumen narrowing of at least 50%. Based on results using A1C to diagnose diabetes based on American Diabetes Association criteria, A1C was a strong predictor of coronary atherosclerosis among women, but not among men who did not have previously undiagnosed diabetes.⁴

A1C predicting CAD. The same Austrian research group investigated the power of A1C to predict future CV events by gender.⁵ The same group of 1449 patients without previously known diabetes in the previous study were followed for 4.4 years. At follow-up, the incidence of CV events was 19.5% in women and 25.6% in men, corresponding to annual event rates of 4.4% and 5.5%. Among women, A1C strongly and significantly predicted CV events (adjusted odds ratio [OR] for a 1% increase in A1C was 1.69) while the association between A1C and CV events in men was weaker and statistically not significant (adjusted OR was 1.15).

Biomarkers, diabetes, and CV risk. The giant study of 12,000 patients with T2DM in the SAVOR-TIMI 53 trial found that regardless of baseline risk, a substantial share of stable patients with this disease have signs of ongoing myocardial damage or hemodynamic stress. These conditions were strongly associated with later risk of death from myocardial infarction (MI). Biomarkers measured in the study were high-sensitivity troponin, NT-proBNP, and hsCRP for enrolled patients. Reseachers found a stepwise increase in rates of CV death and MI with higher quartiles of each biomarker.⁶

References

1. Fast facts. American Diabetes Association website. http://professional.diabetes.org/admin/UserFiles/0%20-%20Sean/FastFacts%20March%202013.pdf. Updated March 2013. Accessed March 30, 2014.
2. Regan T. FDA mea culpa part of cautionary tale. Am J Manag Care. 2013;19(SP7):SP242-SP243.
3. Ikeda N, Hara H, Hiroi Y, Nakamura M. Gender specific difference of association between glycated hemoglobin and prevalence or complexity of coronary artery disease. JACC 2014;63(12)suppl A:abstract 1121-326.
4. Saely C, Vonbank A, Rein P, et al. Gender significantly modulates the association of HbA1C with angiographically diagnosed coronary atherosclerosis among subjects without previously known diabetes. JACC 2014;63(12)suppl A:abstract 1121-336.
5. Saely C, Vonbank A, Rein P, et al. HbA1c is a significantly stonger predictor of cardiovascular event risk in women than in men among patients undergoing coronary angiography. JACC 2014;63(12)suppl A:abstract 1121-334.
6. Scirica B, Bhatt D, Braunwald E. Prognostic implications of simultaneious biomarker assessments in patients with type 2 diabetes mellitus: observations from the SAVOR-TIMI 53 trial. JACC 2014;63(12)suppl A:abstract 1121-337.