Preventive cardiology
Chronic Kidney Disease as a Predictor of Cardiovascular Disease (from the Framingham Heart Study)

https://doi.org/10.1016/j.amjcard.2008.02.095Get rights and content

Chronic kidney disease (CKD) is a risk factor for cardiovascular disease (CVD), although shared risk factors may mediate much of the association. CKD and CVD were related in the setting of specific CVD risk factors, and whether more advanced CKD was a CVD risk equivalent was determined. The Framingham Heart Study original cohort (n = 2,471, mean age 68 years, 58.9% women) was studied. Glomerular filtration rate was estimated (eGFR) using the simplified Modification of Diet in Renal Disease Study equation. CKD was defined as eGFR <59 (women) and <64 ml/min/1.73 m2 (men), and stage 3b CKD was defined as eGFR of 30 to 44 (women) and 30 to 50 ml/min/1.73 m2 (men). Cox proportional hazard models adjusting for CVD risk factors were used to relate CKD to CVD. Effect modification by CVD risk factors was tested for. Overall, 23.2% of the study sample had CKD (n = 574, mean eGFR 50 ml/min/1.73 m2) and 5.3% had stage 3b CKD (n = 131, mean eGFR 42 ml/min/1.73 m2). In multivariable models (mean follow-up 16 years), stage 3 CKD was marginally associated with CVD (hazard ratio [HR] 1.17, 95% confidence interval [CI] 0.99 to 1.38, p = 0.06), whereas stage 3b CKD was associated with CVD (HR 1.41, 95% CI 1.05 to 1.91, p = 0.02). Testing CVD risk equivalency, the risk of CVD for stage 3b CKD in subjects with previous CVD was significantly lower compared with subjects with previous CVD and no stage 3b CKD (age- and sex-adjusted HR for CVD 0.66, 95% CI 0.47 to 0.91, p = 0.01). Low high-density lipoprotein cholesterol modified the association between CKD and CVD (p = 0.004 for interaction). Stage 3b CKD was associated with CVD, but was not a CVD risk equivalent. In conclusion, CVD risk in the setting of CKD is higher in the setting of low high-density lipoprotein cholesterol.

Section snippets

Methods

The Framingham Heart Study is a community-based prospective cohort study of CVD and its risk factors that began in 1948, consisting of 5,209 men and women in the original cohort.1 Subjects were invited to attend examinations every 2 years. The study sample for the present investigation consisted of original-cohort subjects attending examination cycle 15 (1977 to 1979). Of 2,632 participants attending the 15th examination cycle, 67 had missing covariate data and 94 had missing creatinine values,

Results

Mean age of our study sample was 68 years, and 58.9% were women. Mean overall follow-up was 16 years. In study subjects, 574 (23.2%) had CKD. Of these, 131 (22.8%) had stage 3b CKD. Those with CKD were older, tended to have lower mean HDL cholesterol, and had a higher prevalence of hypertension and diabetes (Table 1). Relative to those with stage 3a CKD, subjects with stage 3b CKD were older, more likely to be hypertensive and have diabetes, and had high rates of prevalent CVD. eGFR in those

Discussion

In a community-based cohort of men and women, stage 3 CKD was associated with a 20% increased risk of CVD and CHD after adjustment for age and sex, whereas stage 3b CKD was associated with a 50% increased risk of CVD, which remained significant in multivariable-adjusted models. CKD and stage 3b CKD were associated with all-cause mortality in age- and sex-adjusted models, but not after accounting for CVD risk factors and prevalent CVD. Stage 3b CKD did not constitute a CVD risk equivalent. The

Acknowledgments

Dr Fox had full access to all data in the study and takes responsibility for the integrity of the data and accuracy of the data analysis. The funding sources had no role in the study design, analyses, or drafting of the manuscript. The National Heart, Lung, and Blood Institute reviews all manuscripts submitted for publication, but was not involved in the decision to publish.

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  • Cited by (0)

    The Framingham Heart Study was supported by the National Heart, Lung, and Blood Institute, Bethesda, Maryland (N01-HC-25195).

    Dr Parikh is currently at Beth Israel Deaconess Medical Center.

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