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Mild renal dysfunction and long-term adverse outcomes in women with chest pain: results from the National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation (WISE).

ABSTRACT: BACKGROUND:Chronic kidney disease (CKD) is associated with accelerated atherosclerosis and adverse cardiovascular outcomes, but mechanisms are unclear. We hypothesized that mild CKD independently predicts adverse outcomes in women with symptoms and signs of ischemia. METHODS:We categorized 876 women from the Women's Ischemia Syndrome Evaluation cohort according to estimated glomerular filtration rate (eGFR) (eGFR ?90 mL/min per 1.73 m(2) [normal], 60-89 mL/min per 1.73 m(2) [mild CKD], ?59 mL/min per 1.73 m(2) [severe CKD]). Time to death from all-cause and cardiovascular causes and major adverse outcomes were assessed by multivariate regression adjusted for baseline covariates. RESULTS:Obstructive coronary artery disease (CAD) was present only in few patients (39%). Even after adjusting for CAD severity, renal function remained a strong independent predictor of all-cause and cardiac mortality (P < .001). Every 10-unit decrease in eGFR was associated with a 14% increased risk of all-cause mortality (adjusted hazard ratio [AHR] 1.14 [1.08-1.20], P < .0001), 16% increased risk of cardiovascular mortality (AHR 1.16 [1.09-1.23], P < .0001), and 9% increased risk of adverse cardiovascular events (AHR 1.09 [1.03-1.15], P = .002). CONCLUSIONS:Even mild CKD is a strong independent predictor of all-cause and cardiac mortality in women with symptoms/signs of ischemia, regardless of underlying obstructive CAD severity, underscoring the need to better understand the interactions between ischemic heart disease and CKD.

SUBMITTER: Mohandas R

PROVIDER: S-EPMC4347936 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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Mild renal dysfunction and long-term adverse outcomes in women with chest pain: results from the National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation (WISE).

Mohandas Rajesh R Segal Mark M Srinivas Titte R TR Johnson B Delia BD Wen Xuerong X Handberg Eileen M EM Petersen John W JW Sopko George G Merz C Noel Bairey CN Pepine Carl J CJ

American heart journal 20150106 3

<h4>Background</h4>Chronic kidney disease (CKD) is associated with accelerated atherosclerosis and adverse cardiovascular outcomes, but mechanisms are unclear. We hypothesized that mild CKD independently predicts adverse outcomes in women with symptoms and signs of ischemia.<h4>Methods</h4>We categorized 876 women from the Women's Ischemia Syndrome Evaluation cohort according to estimated glomerular filtration rate (eGFR) (eGFR ≥90 mL/min per 1.73 m(2) [normal], 60-89 mL/min per 1.73 m(2) [mild ...[more]

PMID: 25728732

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Project description:BackgroundWomen presenting with signs and symptoms of myocardial ischemia frequently have no or nonobstructive coronary artery disease (CAD).ObjectiveThis study aimed to investigate the associations between angiographic measures and longer-term clinical outcomes among women with signs and symptoms of ischemia referred for coronary angiography.MethodsA prospective cohort analysis of women referred for coronary angiography and enrolled in the National Heart, Lung, and Blood Institute-sponsored WISE was performed. An angiographic severity score was prospectively developed, assigning points for any stenosis weighted by stenosis severity, location, and collaterals and was then tested for prediction for adverse outcome in 917 women, over a median of 9.3 years.SettingThe study was conducted in referral centers.PatientsWomen with signs and/or symptoms of myocardial ischemia referred for coronary angiography were consecutively consented and enrolled in a prospective study.Main outcome measuresMain outcomes included first occurrence of cardiovascular death or nonfatal myocardial infarction. Hospitalization for angina was a secondary outcome.ResultsCardiovascular death or myocardial infarction at 10 years occurred in 6.7%, 12.8%, and 25.9% of women with no, nonobstructive, and obstructive CAD (P < .0001), respectively. Cumulative 10-year cardiovascular death or myocardial infarction rates showed progressive, near-linear increases for each WISE CAD severity score range of 5, 5.1 to 10, 10.1 to 20, 20.1 to 50, and >50. The optimal threshold in the WISE severity score classifications for predicting cardiovascular mortality was >10 (eg, 5.0-10 vs 10.1-89), with both a sensitivity and specificity of 0.64 and an area under the curve of 0.64 (P = .02, 95% CI 0.59-0.68).ConclusionsAmong women with signs and symptoms of ischemia, nonobstructive CAD is common and associated with adverse outcomes over the longer term. The new WISE angiographic score appears to be useful for risk prediction in this population.

Project description:Paraoxonase (PON), a high-density lipoprotein-associated enzyme, is believed to protect against low-density lipoprotein oxidation and thus affects the risk of coronary artery disease (CAD). Three polymorphisms in the PON1 (Leu55Met and Gln192Arg) and PON2 (Ser311Cys) genes have been shown to be associated with the risk of CAD in several European or European-derived populations. In the present study, we examined the associations between these three markers and the severity of CAD as determined by the number of diseased coronary artery vessels in 711 subjects (589 whites and 122 blacks) from the Women's Ischemia Syndrome Evaluation (WISE) study. WISE is a National Heart, Lung, and Blood Institute-sponsored multicenter study designed to address issues related to ischemic-heart-disease recognition and diagnosis in women. Subjects were classified as having normal/minimal CAD (<20% stenosis), mild CAD (20%-49% stenosis), and significant CAD (>/=50% stenosis). The women who had >/=50% stenosis were further classified into groups with one-, two-, or three-vessel disease if any of the three coronary arteries had diameter stenosis >/=50%. No significant association was found between the PON polymorphisms and stenosis severity in either white or black women. However, among white women, when data were stratified by the number of diseased vessels, the frequency of the PON1 codon 192 Arg/Arg genotype was significantly higher in the group with three-vessel disease than in the other groups (those with one-vessel and two-vessel disease) combined (17.02% vs. 4.58%; P=.0066). Similarly, the frequency of the PON2 codon 311 Cys/Cys genotype was significantly higher in the group with three-vessel disease than in the other groups combined (15.22% vs. 4.61%; P=.018). The adjusted odds ratios for the development of three-vessel disease were 2.80 (95% confidence interval 1.06-7.37; P=.038) for PON1 codon 192 Arg/Arg and 3.68 (95% confidence interval 1.26-10.68; P=.017) for PON2 codon 311 Cys/Cys. Our data indicate that the severity of CAD, in terms of the number of diseased vessels, may be affected by common genetic variation in the PON gene cluster, on chromosome 7.

Dataset Information

Mild renal dysfunction and long-term adverse outcomes in women with chest pain: results from the National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation (WISE).

Publications

Mild renal dysfunction and long-term adverse outcomes in women with chest pain: results from the National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation (WISE).

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