From the Journals

Diabetes becoming less potent risk factor for CVD events



Diabetes persists as a risk factor for cardiovascular events, but where it once meant the same risk of heart attack or stroke as cardiovascular disease itself, a large Canadian population study reports that’s no longer the case. Thanks to advances in diabetes management over the past quarter century, diabetes is no longer considered equivalent to CVD as a risk factor for cardiovascular events, researchers from the University of Toronto reported.

The retrospective, population-based study used administrative data from Ontario’s provincial universal health care system. The researchers created five population-based cohorts of adults at 5-year intervals from 1994 to 2014, consisting of 1.87 million adults in the first cohort and 1.5 million in the last. In that 20-year span, the prevalence of diabetes in this population tripled, from 3.1% to 9%.

“In the last 25 years we’ve seen wholesale changes in the way people approach diabetes,” lead study author Calvin Ke, MD, PhD, an endocrinologist and assistant professor at the University of Toronto, said in an interview. “Part of the findings show that diabetes and cardiovascular disease were equivalent for risk of cardiovascular events in 1994, but by 2014 that was not the case.”

Dr. Calvin Ke, an endocrinologist and assistant professor at the University of Toronto

Dr. Calvin Ke

However, Dr. Ke added, “Diabetes is still a very strong cardiovascular risk factor.”

The investigators for the study, reported as a research letter in JAMA, analyzed the risk of cardiovascular events in four subgroups: those who had both diabetes and CVD, CVD only, diabetes only, and no CVD or diabetes.

Between 1994 and 2014, the cardiovascular event rates declined significantly among people with diabetes alone, compared with people with no disease: from 28.4 to 12.7 per 1,000 person-years, or an absolute risk increase (ARI) of 4.4% and a relative risk (RR) more than double (2.06), in 1994 to 14 vs. 8 per 1,000 person-years, and an ARI of 2% and RR less than double (1.58) 20 years later.

Among people with CVD only, those values shifted from 36.1 per 1,000 person-years, ARI of 5.1% and RR of 2.16 in 1994 to 23.9, ARI of 3.7% and RR still more than double (2.06) in 2014.

People with both CVD and diabetes had the highest CVD event rates across all 5-year cohorts: 74 per 1,000 person-years, ARI of 12% and RR almost four times greater (3.81) in 1994 than people with no disease. By 2014, the ARI in this group was 7.6% and the RR 3.10.

The investigators calculated that event rates from 1994 to 2014 declined across all four subgroups, with rate ratios of 0.49 for diabetes only, 0.66 for CVD only, 0.60 for both diabetes and CVD, and 0.63 for neither disease.

Shift in practice

The study noted that the shift in diabetes as a risk factor for heart attack and stroke is “a change that likely reflects the use of modern, multifactorial approaches to diabetes.”

“A number of changes have occurred in practice that really focus on this idea of a multifactorial approach to diabetes: more aggressive management of blood sugar, blood pressure, and lipids,” Dr. Ke said. “We know from the statin trials that statins can reduce the risk of heart disease significantly, and the use of statins increased from 28.4% in 1999 to 56.3% in 2018 in the United States,” Dr. Ke said. He added that statin use in Canada in adults ages 40 and older went from 1.2% in 1994 to 58.4% in 2010-2015. Use of ACE inhibitors and angiotensin receptor blockers for hypertension followed similar trends, contributing further to reducing risks for heart attack and stroke, Dr. Ke said.

Dr. Ke also noted that the evolution of guidelines and advances in treatments for both CVD and diabetes since 1994 have contributed to improving risks for people with diabetes. SGLT2 inhibitors have been linked to a 2%-6% reduction in hemoglobin A1c, he said. “All of these factors combined have had a major effect on the reduced risk of cardiovascular events.”

Dr. Prakash Deedwania of the University of California, San Francisco

Dr. Prakash Deedwania

Prakash Deedwania, MD, professor at the University of California, San Francisco, Fresno, said that this study confirms a trend that others have reported regarding the risk of CVD in diabetes. The large database covering millions of adults is a study strength, he said.

And the findings, Dr. Deedwania added, underscore what’s been published in clinical guidelines, notably the American Heart Association scientific statement for managing CVD risk in patients with diabetes. “This means that, from observations made 20-plus years ago, when most people were not being treated for diabetes or heart disease, the pendulum has swung,” he said.

However, he added, “The authors state clearly that it does not mean that diabetes is not associated with a higher risk of cardiovascular events; it just means it is no longer equivalent to CVD.”

Managing diabetes continues to be “particularly important,” Dr. Deedwania said, because the prevalence of diabetes continues to rise. “This is a phenomenal risk, and it emphasizes that, to really conquer or control diabetes, we should make every effort to prevent diabetes,” he said.

Dr. Ke and Dr. Deedwania have no relevant financial relationships to disclose.

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