Diabetes, Heart Attack, and Stroke a Lethal Combination

Miriam E Tucker

July 08, 2015

Diabetes, stroke, and myocardial infarction (MI) each double the risk of death alone and multiply the risk further when the trio is combined, a new study finds.

Results from a new analysis of mortality in people with "cardiometabolic multimorbidity" were published in the July 7 issue of the Journal of the American Medical Association by Emanuele Di Angelantonio, MD, of the University of Cambridge, United Kingdom, and his coinvestigators in the UK's Emerging Risk Factors Collaboration (ERFC).

Among 689,300 people from 91 prospective cohorts with baseline data from 1960 to 2007, follow-up at about 13 years revealed that those who had a history of diabetes, stroke, or MI were about twice as likely to have died as those who had none of those cardiometabolic conditions. With two of them, the death rate quadrupled, and with all three, the death rate was eightfold.

For those aged 60, having all three conditions wipes around 15 years off life expectancy, and for younger adults, around the age of 40, life is cut short by a more dramatic 20 years — eclipsing the reduction in life expectancy seen with smoking or HIV infection, the researchers show.

The results were somewhat surprising, Dr Di Angelantonio told Medscape Medical News, noting that "given that the conditions we studied — diabetes, heart attack, and stroke — share several risk factors, it could be expected that the combination of these [would] not be multiplicative."

Previous studies have mainly focused on individuals with one cardiometabolic condition alone. This is the first study to precisely quantitate the effect of "cardiometabolic multimorbidity," a term that has been used previously but has not been precisely defined. Here, the authors define it as the presence of two or all three of the conditions studied.

"These results are of main use for clinicians and policy makers and emphasize, for example, the importance of measures to prevent cardiovascular disease in people who already have diabetes and, conversely, to avert diabetes in people who already have cardiovascular disease. However, at the same time, we must not lose sight of tackling these [individual] serious conditions within the wider population," Dr Di Angelantonio stressed.

Multiplicative Effect of All Three Conditions

Of the total 689,300 study participants, 3.6% had diabetes at enrollment, 1.2% had a history of stroke, and 3.1% had experienced an MI. Between 0.2% and 0.5% had two of those cardiometabolic conditions at baseline, and 0.1% (541) had all three. A total 128,843 died during a median follow-up of 12.8 years.

Among study subjects with none of the three conditions at baseline, the sex-adjusted mortality rate at age 60 years was 6.8 per 1000 person-years at risk.

By contrast, the age- and sex-adjusted mortality rates were 15.6 among those with a history of diabetes, 16.1 for those with stroke, 16.8 with MI, and between 32.0 and 32.8 for those with two of the conditions.

For those with all three, the death risk was 59.5 per 1000 person-years.

Compared with people with none of the conditions at baseline and adjusted for age and sex, the hazard ratios for mortality were 1.9 for those with a history of diabetes, 2.1 for stroke, 3.7 for MI, and between 3.5 and 3.8 for those with two of the conditions. Having all three conditions raised the risk 6.9-fold.

All of those increases were statistically significant compared with those with none of the three conditions. The hazard ratios were stronger among women than men for those with diabetes only, stroke only, and those with both diabetes and MI. Adjusting for total and HDL cholesterol, systolic blood pressure, and body mass index attenuated the results slightly, but they remained significant.

By death cause and adjusted for age and sex, individuals with all three conditions at baseline had an 11.8 times greater risk for cardiovascular mortality, 2.1-fold greater risk for cancer death, and 7.9-fold higher risk for death from nonvascular, noncancer causes.

Similar results were seen with a second analysis carried out among 499,808 participants from a more recent database, the UK Biobank, who were recruited during 2006–2010.

How Much Life Is Lost?

Dr Di Angelantonio and colleagues estimate that at the age of 60 years, men with any two of the cardiometabolic conditions studied would have an average 12 years of reduced life expectancy, and men with all three conditions would lose 14 years of life. For women at age 60 years, the corresponding estimates were 13 years and 16 years.

The estimates were even more dramatic for younger adults. At the age of 40 years, the reduction in life expectancy for men with all three conditions would be 23 years, and for women at the same age, 20 years.

The overall mortality findings seen with cardiometabolic multimorbidity roughly equate to those of other longevity-reducing conditions such as lifelong smoking (about 10 years reduced life expectancy) and HIV infection (11 years), the authors note.

They add that the problem might be proportionately greater in the United States, where the prevalence of cardiometabolic multimorbidity is 3%, compared with the 1% seen in this UK cohort.

"Our results highlight the need to balance the primary prevention and secondary prevention of cardiovascular disease," they conclude.

Dr Di Angelantonio has received personal fees from Elsevier (France). Disclosures for the coauthors are listed in the article.

JAMA. 2015;314:52-60. Abstract

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