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Only Long-Term Diabetes Is a "CHD Risk Equivalent"

Posted: Saturday, April 23, 2011

Diabetes mellitus is associated with an increased risk of major CHD events and all-cause mortality when compared with individuals without diabetes, but only early-onset diabetes appears to be an equivalent CHD risk factor.

In a prospective study of more than 4,000 middle-aged men, a diagnosis of diabetes in patients 60 years of age and older, with a mean diabetes duration of five years, had a CHD risk half that of patients who were diagnosed with diabetes before age 60 and who had diabetes for more than 16 years. In the early-onset diabetes patients, the risk of death and vascular events was equivalent to patients with a prior MI.

The results, according to lead investigator Dr. S Goya Wannamethee (University College London, UK) and colleagues suggest "that a longer duration of diabetes may be necessary to raise risks toward a CHD risk equivalent."

In an editorial accompanying the study, Dr. Iskandar Idris (University of Sheffield, UK) points out that CHD risk equivalence remains a controversial topic since it was proposed more than 10 years ago. Current cholesterol guidelines urge clinicians to treat patients with diabetes to low LDL-cholesterol targets -- to less than 100 mg/dL -- even though there is a lack of evidence to support the target value. Despite this, and given the safety and effectiveness of statins, basing target levels on the presence or absence of diabetes is "practical," writes Idris, but such an approach needs to be balanced against the harms of prescribing the drugs to all patients on the basis of diabetes.

"Correctly identifying and treating individuals who are most at risk of CHD will confer the most cost-effective public-health strategy for primary prevention of CHD," writes Idris. "To this end, the need to reconcile any discordance between the impact of age threshold and disease duration on CHD risk stratification in patients with diabetes is important."

In the study, Wannamethee and colleagues used data from the British Regional Heart Study, a prospective study of cardiovascular disease of men from 24 British towns who underwent screening from 1978 to 1980. Of the 4,045 men age 60 to 79 years old participating in this analysis, individuals were classified as having no prior diabetes or MI, late-onset diabetes (diagnosed >60 years of age), early-onset diabetes (diagnosed <60 years of age), or having a prior MI. During follow-up, there were 373 major CHD events and 1,112 deaths from all causes.

Early- and late-onset diabetes were both associated with an increased risk of major CHD, cardiovascular disease (including cardiovascular disease mortality and nonfatal MI), and all-cause mortality compared with individuals without diabetes, even after adjustment for various risk factors, including C-reactive protein (CRP). The risk, however, was significantly higher among individuals who developed diabetes before 60 years old -- those with an average disease duration of 16 years -- than among those who developed diabetes later in life. Those who developed diabetes earlier in life had a risk of CHD and cardiovascular disease similar to men with a prior MI.

Diabetes and MI Status and Adjusted Hazard Ratios of Clinical Events
No diabetes and no
prior MI (n=3197)
diabetes (n=307)
diabetes (n=107)
Men with prior MI and
no diabetes (n=368)
Major coronary
heart disease
1.0 1.54 (1.07–2.21) 2.39 (1.41–4.05) 2.51 (1.88–3.36)
cardiovascular disease
1.0 1.37 (1.01–1.84) 2.08 (1.33–3.25) 2.17 (1.71–2.77)
All-cause mortality 1.0 1.31 (1.06–1.62) 1.68 (1.19–2.38) 1.48 (1.22–1.78)
Adjusted for age, smoking, alcohol consumption, social factors, body-mass index, physical activity, stroke, blood pressure, HDL and total cholesterol, respiratory factors, C-reactive protein, von Willebrand factor levels, and estimated glomerular filtration rate

The investigators also performed an analysis of diabetes duration and risk of major cardiovascular disease events and total mortality. Compared with those who had diabetes less than two years, only those with diabetes for more than eight years had an increased risk of cardiovascular disease and death. "Overall, our observations plus prior research extend data from previous studies suggesting that CHD risk in patients with diabetes escalates significantly with disease duration and approaches CHD risk equivalence only when disease duration is beyond eight years," write Wannamethee and colleagues.

The group suggests that individuals developing diabetes later in life might be less insulin resistant and have better beta-cell function. In addition, diabetes duration exposes individuals to longer chronic hyperglycemia. "The clinical implication is that, although 10-year CHD risk for newly diagnosed diabetes may not be very high, CHD risk beyond 10 years or indeed lifetime risk will be much higher," they write.

In his editorial, Idris notes that setting disease-duration thresholds for CHD risk equivalence will depend on other factors, such as age, sex, and maybe even ethnicity, and that this might become redundant in individuals who are very old and already have a high absolute risk. "Clearly, in that scenario, the risks and benefits of implementing an aggressive CHD risk-reduction strategy will need to be considered individually rather than from a public-health perspective," he concludes.

Source:, Wannamethee SG, Shaper AG, Whincup PH, et al. Impact of diabetes on cardiovascular disease risk and all-cause mortality in older men. Arch Intern Med 2011; 171:404-410. Idris I. Diabetes and cardiovascular risk equivalency. Arch Intern Med 2011; 171:410-411.

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