Atlanta, GA - The negative impact of diabetes on cardiovascular mortality persists into old age, with elderly people who have diabetes being twice as likely to die as their nondiabetic peers, a new observational study has found [1].

Dr Richard A Kronmal (University of Washington, Seattle) and colleagues report their findings online October 16, 2006 in PLoS Medicine. "The relative risk [of CVD mortality] reported herein is far more noteworthy and of greater public-health impact than a similar relative risk in a middle-aged population," they note. "Elderly people often receive less intensive management of CVD risk factors than younger individuals. Our findings strengthen the rationale for the opposite approach."

In an accompanying editorial [2], Drs Andre Pascal Kengne and Anushka Patel (University of Sydney, Australia) say the new data "make an important contribution to our knowledge of morbidity and mortality associated with diabetes mellitus in older adults."

Kronmal et al note that most studies on the burden of diabetes mellitus have been conducted in middle-aged populations and have often been adjusted only for traditional risk factors. Using the Cardiovascular Health Study (CHS), a longitudinal observational study of adults aged 65 or older, they assessed mortality in older people with diabetes treated with oral hypoglycemic agents (OHGAs) and insulin, adjusting for nontraditional (eg, inflammation, subclinical vascular disease, and psychosocial factors) as well as traditional covariates.

The 5372 participants were followed for 11 years (1989-2001); 322 of them (5.5%) were treated with OHGAs and 194 (3.3%) were treated with insulin. Total, CVD, CHD, and non-CVD/noncancer mortality were recorded.

Second author Dr Joshua I Barzilay (Emory University School of Medicine, Atlanta, GA) told heartwire that a recent Scandinavian study "had suggested that diabetes in the over-75s was not a big risk. . . . [But] we found that diabetes mellitus continues to be associated with a deleterious effect on mortality in older adults."

For combined CVD and CHD deaths, adjusted mortality risks were around two and 2.5 times higher, respectively, than in participants without diabetes, they note, stating that these estimates are similar to those from studies of older individuals with diabetes from prior decades, which adjusted only for traditional CVD risk factors.

Thus, two conclusions can be drawn, they note. First, "given the decreasing rate of CVD and CHD mortality in the general population but the unvarying relative risk of mortality associated with diabetes, it follows that older adults with diabetes are experiencing the same rate of decline in CVD and CHD mortality as people without diabetes."

This is important, as there have been conflicting data as to whether diabetics were or were not experiencing the same decline in CVD and CHD mortality as nondiabetics, Barzilay explained.

Second, the additional adjustment for nontraditional risk factors "did not have much of an impact on mortality," he notes, a somewhat puzzling finding, given that subclinical cardiovascular disease is known to be a strong predictor of clinical disease.

In their editorial, Kengne and Patel say: "These data provide reliable evidence that diabetes is an important adverse risk factor among older adults, with estimates of the strength of the associations comparable to published data for younger cohorts.

"These data confirm that older adults with diabetes are at very high absolute risk of death from cardiovascular causes (4% to 5% per year). Thus, strategies aimed at reducing these risks should be aggressively pursued among such individuals, wherever possible."

Kronmal et al also found that women with diabetes vs women without had a greater relative total mortality risk compared with men (2.28 vs 1.80). When this risk was categorized by treatment type, it appeared that women who took OHGAs had a mortality risk similar to men, while those treated with insulin had a much higher relative mortality than men, particularly in terms of deaths from renal and infectious causes.

"Thus, the overall increased mortality of women than men with diabetes appears to be accounted for by insulin therapy. This finding has not, to our knowledge, yet been reported," they state.

Barzilay says this is an interesting finding, and that he has also observed a three- to fourfold increased risk of coronary heart disease in people with diabetes and high morning insulin levels in another study [3]. "We plan to look at this in more detail in larger studies with greater numbers."

Kengne and Patel say the observations that the relative risk of mortality associated with diabetes, particularly that due to infectious or renal causes, was significantly greater among individuals treated with insulin compared with those receiving OHGAs and that women with diabetes on insulin had a particularly high risk of death compared with women without diabetes are "interesting . . . [but] can only be considered hypothesis generating."

Ongoing clinical trials, such as ADVANCE and ACCORD, should help shed further light on these questions, they note.

ACCORD is testing three complementary medical strategies for type 2 diabetes in just over 10 000 patients. The three specific hypotheses are:

• Does a strategy targeting HbA1_c of <6.0% reduce the rate of CVD events more than one that targets an HbA1_c of 7.0% to 7.9%?
• In the context of good glycemic control, how does using a fibrate to raise HDL/lower triglyceride levels in addition to a statin for treatment of LDL reduce the rate of CVD events compare with just using a statin alone?
• In the context of good glycemic control, does targeting a systolic BP of <120 mm Hg reduce the rate of CVD events more than one that targets SBP <140 mm Hg?

The primary end point of ACCORD will be the first occurrence of a major cardiovascular disease event, specifically nonfatal MI, nonfatal stroke, or cardiovascular death.

The ADVANCE trial is trying to determining the effects of blood-pressure lowering and intensive glucose lowering on macrovascular and microvascular disease in 11 140 individuals with early type 2 diabetes.