Risk Factor Reduction Cuts Excess CV Risk in Diabetes

Miriam E. Tucker

August 28, 2018

The excess cardiovascular (CV) risk associated with type 2 diabetes can almost be eliminated by reaching targets for five other risk factors, data from a large Swedish cohort study suggests.

The study, published online August 16 in the New England Journal of Medicine, included nearly 300,000 people with type 2 diabetes and over 1 million matched controls who were followed for about 6 years.

Participants who achieved target levels of hemoglobin A1c (HbA1c), LDL-cholesterol, albuminuria, and blood pressure and who quit smoking came close to eliminating the excess risks for all-cause death, myocardial infarction, and stroke compared with the general population.

"The study indicates that having all five risk-factor variables within the target ranges could theoretically eliminate the excess risk of acute myocardial infarction," write Aidin Rawshani, MD, of the Sahlgrenska Academy, University of Gothenburg, Sweden, and colleagues.

However, they note that even with all the targets achieved, the group with diabetes were still at increased risk for hospitalization for heart failure.

Typically, patients with type 2 diabetes have two to four times the risks of death and cardiovascular events as the general population.

In an accompanying editorial, Steven A. Schroeder, MD, of the Department of Medicine, University of California, San Francisco, writes that the results "provide clear support for active management of risk factors."

Schroeder cautions, though, "that pathways to target levels of risk-factor variables are not always straightforward and often involve issues of lifestyle, adherence to medication, and other behaviors that are hard to modify, despite best attempts. For vulnerable populations, risk factor control may be especially challenging, as shown by the widening health gap between social classes."

Linear Relationship With Risk Factors and Death, CV Outcomes

The cohort study included 271,174 patients with type 2 diabetes who were registered in the Swedish National Diabetes Register, matched for age, sex, and county with 1,355,870 participants from the general population.

Risk factor targets assessed were HbA1c ≥ 7.0% (≥ 53 mmol/mol), systolic and diastolic blood pressure ≥ 140/80 mm Hg, albuminuria (microalbuminuria or macroalbuminuria), current smoking at study entry, and LDL-cholesterol ≥ 2.5 mmol/L (97 mg/dL).

During a median follow-up of 5.7 years, 175,345 participants died, including 13.9% of the 37,825 with diabetes and 10.1% of those without. 

The researchers found a stepwise increase in hazard ratios for each additional variable that didn't meet the target range, although the incremental risks for cardiovascular events and diabetes-associated deaths decreased from younger to older age groups.

Regardless of age, those who had none of the risk factors had no significant increased risk for mortality, acute myocardial infarction, or stroke compared with the control group. However, those with diabetes of all ages up to 80 years and no risk factors still had a significantly increased risk of heart failure, with hazard ratios ranging from 2.40 for those younger than 55 years to 1.42 for those 65–80 years.

In contrast, for those younger than 55 years with all five risk factors, the hazard ratios for mortality, myocardial infarction, stroke, and heart failure compared with controls of that age group were 4.99, 7.69, 6.22, and 11.35, all highly significant.

The strongest predictors of risk of death among those with type 2 diabetes were smoking, physical activity, marital status, HbA1c level, and use of statins. For acute myocardial infarction, the strongest predictors were HbA1c, systolic blood pressure, LDL-cholesterol, physical activity, and smoking.

For stroke, the strongest predictors were HbA1c, systolic blood pressure, diabetes duration, physical activity, and atrial fibrillation.

Factors that predicted hospitalization for heart failure were primarily atrial fibrillation and a body mass index outside the target range, low estimated glomerular filtration rate, and high HbA1c level.

Smoking Cessation: A Worthy Target

Schroeder points out that, among other things, these data suggest a major role for smoking cessation efforts in diabetes management. The smoking rate in this Swedish population was just 17% during the study period (1998-2012). The rate has now dropped to 5%, the lowest in the world, due in part to the popularity of snus, an oral, noncombustible moist powdered nicotine-containing tobacco preparation.

"The low smoking [rate] in Sweden...[indicates] that much greater reduction in smoking prevalence is possible. That laudable goal deserves aggressive action."

The study was supported by grants from the Swedish Association of Local Authorities and Regions, Swedish State, Region Västra Götaland, Swedish Diabetes Foundation, Swedish Heart and Lung Foundation, Swedish Research Council, Wilhelm and Martina Lundgren Science Foundation, and Swedish Council for Health, Working Life, and Welfare. Rawshani and Schroeder have reported no relevant financial relationships.

N Engl J Med. 2018; 379:633-644. Abstract, Editorial

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