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) (original) (raw)
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Journal of Clinical Medicine
Chronic kidney disease (CKD) is associated with an increased cardiovascular risk in a broad spectrum of populations. However, the risk associated with a reduced estimated glomerular filtration rate (eGFR) in patients with stable coronary artery disease receiving standard care in the modern era, independently of baseline cardiovascular disease, risk factors, and comorbidities, remains unclear. We analyzed data from 21,911 patients with stable coronary artery disease, enrolled in 45 countries between November 2009 and July 2010 in the CLARIFY registry. Patients with abnormal renal function were older, with more comorbidities, and received slightly lower-although overall high-rates of evidence-based secondary prevention therapies than patients with normal renal function. The event rate of patients with CKD stage 3b or more (eGFR <45 mL/min/1.73 m 2) was much higher than that associated with any comorbid condition. In a multivariable adjusted Cox proportional hazards model, lower eGFR was independently associated with a graded increased risk of cardiovascular mortality, with adjusted HRs (95% CI) of 0.98 (0.81-1.18), 1.31 (1.05-1.63), 1.77 (1.38-2.27), and 3.12 (2.25-4.33) for eGFR 60-89, 45-59, 30-44, and <30 mL/min/1.73 m 2 , compared with eGFR ≥90 mL/min/1.73 m 2. A strong graded independent relationship exists between the degree of CKD and cardiovascular mortality in this large cohort of patients with chronic coronary artery disease, despite high rates of
Chronic Kidney Disease as a Predictor of Cardiovascular Disease (from the Framingham Heart Study)
The American Journal of Cardiology, 2008
Chronic kidney disease (CKD) is a risk factor for cardiovascular disease (CVD), although shared risk factors may mediate much of the association. We related CKD and CVD in the setting of specific CVD risk factors and determined whether more advanced CKD was a CVD risk equivalent. The Framingham Heart Study original cohort (n=2471, mean age 68 years, 58.9% women) was studied. Glomerular filtration rate (eGFR) was estimated using the simplified Modification of Diet in Renal Disease Study equation. CKD was defined as eGFR < 59 mL/min per 1.73 m 2 (women) and < 64 (men) and Stage 3b CKD defined as eGFR 30-44 (women) and 30-50 (men). Cox Proportional Hazard models adjusting for CVD risk factors were used to relate CKD to CVD. We tested for effect modification by CVD risk factors. Overall, 23.2% of the study sample had CKD (n=574; mean eGFR 50 mL/min per 1.73 m 2 ) and 5.3% had Stage 3b CKD (n=131; mean eGFR 42 mL/min per 1.73 m 2 ). In multivariable models (mean follow-up time 16 years), Stage 3 CKD was marginally associated with CVD (HR=1.17, 95% CI 0.99-1.38, p=0.06), whereas Stage 3b CKD was associated with CVD [HR=1.41, 95% CI 1.05-1.91, p=0.02]. Upon testing CVD risk equivalency, the risk of CVD for Stage 3b CKD among participants with prior CVD was significantly lower as compared to participants with prior 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 HDL modified the association between CKD and CVD (p-value=0.004 for interaction). Stage 3b CKD is associated with CVD but is not a CVD risk equivalent. In conclusion, CVD risk in the setting of CKD is higher in the setting of low HDL cholesterol. GFR 30-44 mL/min per 1.73 m 2 in women and 30-50 mL/min per 1.73 m 2 in men Am J Cardiol. Author manuscript; available in PMC 2009 July 1.
Journal of Women's Health, 2010
Objectives: To evaluate the association between renal dysfunction and long-term prognosis among middle-aged women surviving an acute coronary syndrome (ACS). Methods: The Stockholm Female Coronary Risk Study included 291 women <66 years of age, hospitalized for an ACS during the years 1991-1994 in the greater Stockholm area. All patients underwent clinical screening for cardiovascular prognostic factors, including blood samples 3 to 6 months after the event. Creatinine clearance (CCr) was calculated using the Cockcroft-Gaults formula and related to adverse outcome. Hazard ratios (HR) for all-cause and cardiovascular mortality, respectively, in each tertile of CCr, were estimated using Cox proportional hazards regression.
Renal Function and Coronary Microvascular Dysfunction in Women with Symptoms/Signs of Ischemia
Chronic kidney disease (CKD) is more prevalent among women and is associated with adverse cardiovascular events. Among women with symptoms and signs of ischemia enrolled in the Women's Ischemia Syndrome Evaluation (WISE), a relatively high mortality rate was observed in those with no obstructive coronary artery disease. Coronary microvascular dysfunction or reduced coronary flow reserve (CFR) was a strong and independent predictor of adverse outcomes. The objective of this analysis was to determine if renal function was associated with coronary microvascular dysfunction in women with signs and symptoms of ischemia.
Journal of Cardiology, 2010
Normal stress myocardial perfusion images (MPI) generally show good prognosis for cardiovascular events. However, chronic kidney disease (CKD) is one of the important risk factors for coronary artery disease (CAD), and the interpretation of normal stress MPI has not been well established in CKD patients with no evidence of CAD. The purpose of this study was to evaluate the long-term prognostic value of stress MPI in CKD patients with no evidence of myocardial ischemia or infarction. Patients who had no history but were suspected of CAD and had normal stress MPI (n=307, male=208, age=67 years, CKD/non-CKD=46/261) were followed-up for 4.5 years. CKD was defined as a glomerular filtration ratio of &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;60 ml/min/1.73 m(2) and/or persistent proteinuria. Cardiac death, non-fatal myocardial infarction, and unstable angina requiring hospitalization were defined as major cardiac events. Major cardiac events were observed in 3 of 261 (1.1%) non-CKD patients and 6 of 46 (13%) CKD patients (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001, with log-rank test). CKD was an independent risk factor for major cardiac events (hazard ratio=13.1, p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001, multivariate Cox regression analysis). Normal stress MPI does not always promise a good prognosis for major cardiac events. Even in patients with no evidence of CAD from stress MPI, CKD can be an independent and significant risk factor for major cardiac events.
Kidney Dysfunction, Inflammation, and Coronary Events: A Prospective Study
Journal of the American Society of Nephrology, 2004
Kidney dysfunction and high C-reactive protein (CRP) levels are independently associated with coronary events. However, it is unclear whether the risk of coronary events associated with decreased kidney function is at least partially mediated by inflammation and whether the association between inflammatory biomarkers and coronary events is influenced by level of kidney function. With the use of a prospective, nested, case-control study design, the association among kidney function, inflammatory biomarker levels, and coronary events was studied. A total of 244 women who were participants in the Nurses&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; Health Study and had no history of cardiovascular disease received a diagnosis of an incident coronary event (defined as nonfatal myocardial infarction or death as a result of coronary disease) during the follow-up period from 1990 to 1998 and were matched to 486 control subjects. Serum creatinine and inflammatory biomarker levels were measured in blood samples collected in 1989. Creatinine clearance (CrCl) was estimated using creatinine, age, weight, and height. In multivariate analyses, the odds ratio (OR) for a coronary event in women with an estimated CrCl &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;60 ml/min was 2.33 (95% confidence interval [CI], 1.01 to 5.38) compared with those with a CrCl &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; or =90 ml/min. When soluble tumor necrosis factor receptor (sTNFR) I and II levels were added into this model individually, the observed OR for women with CrCl &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;60 ml/min was attenuated. In analyses stratified by estimated CrCl, higher high-sensitivity CRP (hs-CRP), IL-6, and sTNFR I and II levels each were significantly associated with an increased odds of coronary events in women with an estimated CrCl &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; or =74 ml/min but not in women with an estimated CrCl &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; or =75 ml/min. The OR per 5-mg/L unit increase in hs-CRP was 1.68 (95% CI, 1.13 to 2.52) for women with an estimated CrCl &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; or =74 ml/min, compared with 1.23 (95% CI, 0.86 to 1.76) and 0.99 (95% CI, 0.76 to 1.29) for women with an estimated CrCl 75 to 89 and &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; or =90 ml/min, respectively (P = 0.004 for interaction). In conclusion, kidney dysfunction is associated with an increased odds of coronary events, and inflammation, as assessed by higher sTNFR I and II levels, may mediate some of this risk. Higher inflammatory biomarkers levels, specifically, hs-CRP, IL-6, and sTNFR I and II, were significantly associated with coronary events only in women with reduced kidney function. These findings warrant further investigation in other populations.
Mild Renal Insufficiency Is Associated With Angiographic Coronary Artery Disease in Women
Circulation, 2002
Background-Mild renal insufficiency is associated with an increased risk for cardiovascular events in women with coronary artery disease (CAD). However, the relationship between mild renal insufficiency and atherosclerotic CAD in women is not known. Methods and Results-Women with chest pain who were referred for coronary angiography in the NHLBI Women's Ischemia Syndrome Evaluation (WISE) study underwent quantitative coronary angiography, blood measurements of creatinine, lipids, and homocysteine, and assessment of CAD risk factors. Fifty-six women had mild renal insufficiency (serum creatinine 1.2 to 1.9 mg/dL), and 728 had normal renal function (creatinine Ͻ1.2 mg/dL). Creatinine correlated with angiographic CAD severity score (rϭ0.11, PϽ0.004) and maximum coronary artery stenosis (rϭ0.11, PϽ0.003). Compared with women with normal renal function, those with mild renal insufficiency were more likely to have significant angiographic CAD (Ն50% diameter stenosis in Ն1 coronary artery) (61% versus 37%; PϽ0.001) and CAD in multiple vessels (PϽ0.001 for association) and had greater maximum percent diameter coronary stenosis (59Ϯ35% versus 38Ϯ36%; PϽ0.001). Mild renal insufficiency was associated with significant angiographic CAD independent of age and risk factors (ORϭ1.9, 95%CIϭ1.1 to 3.5). After controlling for homocysteine in 509 women, mild renal insufficiency remained predictive of CAD (ORϭ3.2, 95%CIϭ1.4 to 7.2). Conclusions-In women with chest pain, mild renal insufficiency is an independent predictor of significant angiographic CAD. Mildly increased serum creatinine is probably a marker for unmeasured proatherogenic factors. (Circulation. 2002;105:2826-2829.