SAN DIEGO – Tight control of hemoglobin A_1c levels significantly reduces the risk of heart failure in patients with type 1 diabetes, results from a large, long-term study show.

In fact, patients with very poor glycemic control were four times as likely to experience heart failure, compared with their counterparts with optimal glycemic control.

"Because treatment for heart failure improves survival and quality of life, clinicians should be observant of signs of heart failure in management of patients with type 1 diabetes, starting at an early stage," lead author Dr. Marcus Lind wrote in the study, which was presented at the annual scientific sessions of the American Diabetes Association and simultaneously published online in the Lancet on June 25. "Echocardiography might be warranted, especially in the presence of poor glycemic control, long duration of diabetes, or an adverse risk factor profile."

Dr. Lind of the department of medicine at Uddevalla (Sweden) Hospital and his associates used the Swedish national diabetes registry to identify 20,985 patients aged 18 years or older with type 1 disease who had no known heart failure and who were registered between January 1998 and December 2003. They followed the cohort until hospital admission for heart failure, death, or end of follow-up on Dec. 31, 2009 (Lancet 2011 June 25 [doi: 10.1016/S0140-6736(11)60471-6]).

The incidence of heart failure was determined by dividing the number of patient-years of follow-up in a particular HbA_1c category, reported as events per 1,000 years of follow-up. The six HbA_1c categories were less than 6.5%, from 6.5% to less than 7.5%, from 7.5% to less than 8.5%, from 8.5% to less than 9.5%, from 9.5% to less than 10.5%, and 10.5% or greater. Cox regression analysis was used to study possible associations between heart failure and patients’ characteristics.

The mean age of patients was 39 years, and 45% were female; they had had diabetes for a mean of 14 years, and their mean body mass index was 25 kg/m². During a median follow-up of 9 years, 635 patients (3%) were admitted with a primary or secondary diagnosis of heart failure, for an incidence of 3.38 per 1,000 patient-years. The incidence of heart failure increased in a stepwise fashion as HbA_1c levels increased, from an incidence of 1.42 per 1,000 patient-years among patients in the below-6.5% category of HbA_1c to an incidence of 5.20 per 1,000 patient-years among those in the 10.5% or higher category of HbA_1c.

After adjustment for age, sex, duration of diabetes, cardiovascular disease risk factors, acute myocardial infarction, and other comorbidities, a Cox regression analysis revealed that patients with an HbA_1c level of 10.5% or higher were four times more likely to develop heart failure than were those who had an HbA_1c level of less than 6.5%.

Other independent predictors of heart failure included age (hazard ratio, 1.64 per 10-year increase); duration of diabetes (HR, 1.34 per 10-year increase); BMI (HR, 1.05 per 1 kg/m² increase); systolic blood pressure (HR, 1.15 per 10 mm Hg increase); smoking (HR, 1.11-1.90, according to reported frequency); valve surgery (HR, 2.32); atrial fibrillation (HR 1.89); myocardial infarction (HR, 6.42), and ischemic heart disease (HR, 2.9).

"For many years there have observations that poor glycemic control is linked to heart attack and cardiovascular mortality," Dr. Sue Kirkman, senior vice president of medical affairs and community information for the American Diabetes Association, said in an interview at the meeting. "This may be the first time that it’s been shown to be linked to heart failure in a type 1 population."

She called the study "hypothesis-generating," and noted that a long-term randomized trial will be needed to confirm the findings. "It is interesting, because it seems that in type 1 diabetes there may be a stronger link between glucose lowering and cardiac outcomes than in type 2 diabetes," she said.

The researchers acknowledged certain limitations of the study, including its observational design and the fact that only data on hospital admission for heart failure were available from the Swedish national diabetes registry, "so the true incidence of heart failure could be underestimated," they wrote. "Patients with early signs of heart failure, or asymptomatic heart failure detectable by echocardiography, will not have been captured."

The study was supported by an unrestricted grant from AstraZeneca, Novo Nordisk Scandinavia, the Swedish Heart and Lung Foundation, and the Swedish Research Council. Dr. Lind disclosed that he has received honoraria or served as consultant for Bayer, Eli Lilly, Novartis, Novo Nordisk Scandinavia, Medtronic Pfizer, and Sanofi-Aventis; and has been a member of an advisory board for Novo Nordisk Scandinavia.

Glycemic Control Protects Against Heart Failure in Type 1 Diabetes