HbA1c Predicts Cardiovascular Risk

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Hemoglobin A1c level was a better predictor of the risk of cardiovascular

disease (CVD) than simply using a diagnosis of diabetes to establish risk, a

new analysis of two large cohort studies showed.

HbA1c had a greater impact on predicting CVD in women (*P*<0.001), but

prediction also improved significantly in men (*P*=0.039).

The results could prove useful to ongoing discussions about managing CVD

risk in patients with diabetes, investigators reported online in *Archives

of Internal Medicine.*

" These results may be particularly helpful in light of current discussion

around treatment choices for diabetic patients for prevention of CVD,

including use of statins and aspirin, " Nina P. Paynter, PhD, of Brigham and

Women's Hospital in Boston, and co-authors wrote in discussion of their

findings.

" Our results suggest that the use of HbA1c levels as part of overall CVD

risk scores may improve predictive ability in diabetic patients, whose HbA1c

levels are routinely measured in clinical practice. "

Diabetes has a well-established association with CVD risk. Whether the

association varies by HbA1c levels or other CVD risk factors has not been

determined.

The issue has clinical relevance, the authors wrote, because if HbA1c

improved CVD risk prediction, a risk model that included an HbA1c term for

diabetes could be used both for patients who have the disease and those who

don't.

To examine the question, the authors analyzed data on 24,674 women (685 of

whom had diabetes) who participated in the Women's Health Study (WHS) and

11,280 men (563 with diabetes) from the Physicians' Health Study (PHS). The

WHS participants had a median follow-up of 10.2 years, and the PHS

participants had a median follow-up of 11.8 years.

During follow-up in the WHS, 125 CVD events occurred in the women with

diabetes and 666 in those who did not have the disease. In the PHS the 563

men with diabetes had 170 cardiovascular events versus 1,382 in the

nondiabetic men. Diabetes was considered a CVD risk equivalent.

Paynter and colleagues analyzed the effect of adding HbA1c to the 10-year

risk estimates of the National Cholesterol Education Program for Adults (ATP

III) and the Reynolds Risk Score (RRS), which includes C-reactive protein

and parental history of premature myocardial infarction.

The ATP III guidelines define diabetes as a CVD equivalent, meaning that all

patients with diabetes fall into the highest-risk category.

Overall, models that included HbA1c significantly improved discriminatory

power (C statistic 0.177, *P*<0.001) and led to net reclassification

improvement (NRI) of 26.7% for the ATP III (*P*=0.001) and 23.6% for RRS (*P

*=0.003) among diabetic participants in the WHS.

Including HbA1c levels had a more modest impact among diabetic men in the

PHS but still yielded a significant improvement in discriminatory power in

the ATP III model (C statistic 0.039, *P*=0.02) and NRIs of 9.2% for ATP III

(*P*=0.04) and 12.4% for RRS (*P*=0.004).

HbA1c levels also improved prediction as compared with a dichotomous term

for diabetes (versus a risk equivalent) in women (NRI 11.8%, *P*=0.03) but

not in men.

The study had several limitations that were highlighted in an accompanying

editorial. Although the analysis involved almost 36,000 men and women, the

number of diabetic participants (1,248) was modest, and most of them had

well-controlled diabetes, as reflected in an HbA1c of 6.5% to 7.0%, noted

Mark J. Pletcher, MD, of the University of California San Francisco.

Whether enough diabetic participants with elevated HbA1c levels were

included to ensure accurate modeling is unclear, he continued.

Additionally, he noted, the analysis did not show that including HbA1c in a

risk question is superior to use of an indicator variable for diabetes (such

as 1 or -1).

Despite the limitations, the analysis demonstrated the value of allowing

reclassification of diabetic patients by means of HbA1c, as opposed to the

practice of including all diabetic patients in the highest-risk category for

CVD, Pletcher wrote.

Without minimizing the value of including specific markers of CVD risk into

clinical guidelines, Pletcher suggested that guideline committees and

sponsors need to develop strategies for more rapid incorporation of new

developments in CVD risk prediction.

Existence of a standing committee to consider advances in CVD risk

prediction between guideline iterations (often 10 years apart) would also

aid rapid integration into clinical practice, as would development of simple

tools to aid clinicians in implementing new approaches, Pletcher wrote in

conclusion.

The study was supported by F. Hoffmann-La Roche, the National Heart, Lung

and Blood Institute, the National Cancer Institute, and the W.

Reynolds Foundation.

Paynter and co-author Norman A. Mazer disclosed a relationship with F.

Hoffmann-La Roche. Co-author Ridker disclosed relationships with Leducq

Foundation, Roche Diagnostics, Amgen, AstraZeneca, Novartis, Merck, Abbott,

sanofi-aventis, Merck Schering-Plough, Isis, Siemens, and Vascular

Biogenics, and he disclosed that he has a patent interest related to the use

of inflammatory markers in CVD.

Pletcher did not report any financial disclosures.

*Primary source: *Archives of Internal Medicine

Source reference:

Paynter NP, et al " Cardiovascular risk prediction in diabetic men and women

using hemoglobin A1c versus diabetes as a high-risk equivalent " *Arch Intern

Med* 2011;

DOI:10.1001/archinternmed.2011.351.<http://archinte.ama-assn.org/cgi/content/ful\

l/archinternmed.2011.351>

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