Diabetes Raises Risk of Death for Years After a Heart Attack

Liam Davenport

June 30, 2016

Patients with diabetes have a 50% increased risk of dying following an acute myocardial infarction (AMI) compared with those who've had a heart attack but don't have diabetes, the largest study of its kind ever conducted has revealed.

Examining data on more than 700,000 AMI patients, UK researchers found that those with diabetes had a 65% increased risk of death if they had suffered an ST-elevation myocardial infarction (STEMI) and a 39% increased risk of death after non-STEMI, compared with those without diabetes.

Senior author Chris Gale, MD, PhD, of Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, United Kingdom, said: "These results provide robust evidence that diabetes is a significant long-term population burden among patients who have had a heart attack."

"Although these days people are more likely than ever to survive a heart attack, we need to place greater focus on the long-term effects of diabetes in heart-attack survivors," he noted in a University of Leeds press statement.

Speaking to Medscape Medical News, Dr Gale emphasized that, while it is "good news" that a patient has survived a heart attack, this is an indication that, if "they have got active diabetes that's causing end-organ cardiovascular problems…they're high risk and they should be aggressively treated."

He said that includes ensuring that patients are on the right medications and taking their tablets appropriately, that their blood glucose and cholesterol levels and blood pressure are well controlled, and that they follow advice on lifestyle change, such as losing weight, exercising, and stopping smoking: "The partnership between cardiologists, GPs, and diabetologists needs to be strengthened, and we need to make sure we are using established medications as effectively as possible among high-risk individuals."

Dr Gale noted that another question around the increased post-AMI mortality risk among diabetic patients is whether cardiovascular medications are "working equally as well in diabetics as they are in nondiabetics, and if they're not, why."

He added: "Certainly if they're not, why aren't we developing new medications that are more efficacious and that could be diabetes-specific?"

Mike Knapton, MD, associate medical director at the British Heart Foundation, the UK charity that funded the study, said that it is the first work "to conclusively show" that diabetes itself has an adverse effect on survival.

He continued: "This research highlights the need to find new ways to prevent coronary heart disease in people with diabetes and develop new treatments to improve survival after a heart attack."

The study, which was published online in the Journal of Epidemiology and Community Health earlier this month by Oral Alabas, MD, a research fellow at University of Leeds, follows a recent analysis of data from the Examination of Cardiovascular Outcomes With Alogliptin versus Standard of Care (EXAMINE) trial.

As reported by Medscape Medical News, this showed that patients with type 2 diabetes who have previously experienced a nonfatal cardiovascular event have an increased risk of cardiovascular death, particularly among those who experienced prior hospitalization for heart failure.

Up to a Fifth of Heart-Attack Patients Had Diabetes

Dr Alabas and colleagues note that although evidence already suggests that the effect of diabetes on short- and long-term mortality post-MI persists after adjustment for confounding factors, it has not been clear whether this effect remains after correction for the survival of the general population.

So for the current study, they examined data from the Myocardial Ischaemia National Audit Project, which includes all AMI patients admitted to acute hospitals in England and Wales, alongside mortality data from the matching population of 56.9 million individuals.

This yielded a total of 703,920 patients aged 18 years and over who were admitted to 247 hospitals in England and Wales between 2003 and 2013. These consisted of 281,259 cases of STEMI and 422,661 patients with non-STEMI.

Analyzing 1,944,194 person-years at risk, the team compared age, sex, calendar year, and country-specific mortality rates between the general population and STEMI and non-STEMI patients.

The mean age of STEMI and non-STEMI patients was 65.7 years and 71.0 years, respectively. Diabetes was identified in 12.1% of STEMI and 20.4% of non-STEMI patients. The researchers were not able to distinguish from the data whether patients had type 2 diabetes or type 1. Both STEMI and non-STEMI patients with diabetes were more likely than those without diabetes to have had previous AMI, heart failure, and chronic renal failure.

The median time to death was 2.3 years, and 200,360 (28.4%) of the patients included in the study died.

Diabetes patients were more like to die than those without diabetes, at 35.8% vs 25.3%.

Adjusting for age, sex, and year of AMI found that diabetes was associated with a significantly increased risk of death following both STEMI and non-STEMI, at an excess mortality rate ratio of 1.72 and 1.67, respectively (P < .05 for both).

The increased mortality risk associated with diabetes remained even after adjustment for comorbidities, at an excess mortality rate ratio of 1.52 and 1.45 for STEMI and non-STEMI patients, respectively, and after adjustment for cardiovascular treatments, at respective excess mortality rate ratios of 1.56 and 1.39.

Hence, after adjustment for case mix, risk factors, and cardiovascular treatments, as well as correction for mortality from non-CV causes, diabetes is "independently associated with substantial long-term excess mortality following AMI," say the researchers.

And "patients with diabetes continue to be at an elevated risk of death many years after acute myocardial infarction," they stress.

Is There Something Intrinsic to Diabetes That Raises Risk?

Dr Gale explained that, after the researchers adjusted for confounding factors, there remained "a few possibilities" to explain the relationship between diabetes and post-AMI death. One is that there is "something intrinsic to diabetes, as a disease itself," such as endothelial dysfunction, that increases the mortality risk following a heart attack.

It is known that diabetes patients are much more likely to develop heart failure than those without diabetes, for example, but the mechanism behind this remains unknown.

Or, Dr Gale added, it "might be interesting to look at" whether the health-seeking behavior of diabetic patients "is the same as nondiabetics," although he noted this information was not recorded in this study.

"After a heart attack, do diabetics go back and see the general practitioner, the cardiologist, the diabetologist, and get the appropriate care and support [to the same extent as those without diabetes]?" he wondered.

The final possibility is that cardiac drugs are less efficacious in diabetic patients than in those without diabetes. Dr Gale noted that there is "some evidence" that diabetic patients are resistant to the efficacy of aspirin, for example.

"But, again, the mechanism behind that is debatable. Is it at a cellular level, or is because people are not taking their tablets, or is it because of something else? We don't know, and that's what future studies should look into," he concluded.

Recently some of the newer agents for treating type 2 diabetes have shown reductions in cardiovascular mortality in trials of diabetes patients with existing cardiovascular disease, but researchers are still mulling over the findings and possible implications and discussing potential mechanism for this effect, if it turns out to be real.

Earlier this week, an FDA advisory committee narrowly voted in favor of allowing a new labeling claim — that of reduced cardiovascular mortality — for the sodium-glucose cotransporter-2 (SGLT-2) inhibitor empagliflozin (Jardiance, Boehringer Ingelheim/Lilly) based on the results from the EMPA-REG trial in type 2 patients with CVD. It remains to be seen whether the FDA will follow this advice and approve this additional indication.

Dr Gale is funded by the National Institute for Health Research as associate professor and honorary consultant cardiologist. Dr Alabas is funded by ACS Risk Working Group. Disclosures for the coauthors are listed in the article.

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J Epidemiol Community Health 2016. Published online June 15, 2016. Abstract

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