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Relationship between chronic kidney disease and mortality and morbidity among patients with established cardiovascular disease: a community-based cohort study. Liam G Glynn, Donal Reddan, John Newell, John Hinde, Brian Buckley, Andrew W Murphy. Background.
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Relationship between chronic kidney disease and mortality and morbidity among patients with established cardiovascular disease: a community-based cohort study Liam G Glynn, Donal Reddan, John Newell, John Hinde, Brian Buckley, Andrew W Murphy
Background Chronic Kidney disease (CKD) & Cardiovascular disease (CVD A complex relationship? • Recent data: • Tonelli et al, BMJ 2006, Post-MI patients • Go et al, NEJM 2004, General (health-insured) population • Al Suwaidi et al, Circulation 2002, Post-MI patients • Data • Historical • Community-based • Patient Selection • Renal Function Measurement • European Data (Henry, Kidney Int., 2005) CCHSRD Seminar, NUIG, December 5th 2006
Aim and objectives To investigate the relationship between chronic kidney disease and cardiovascular morbidity and mortality • in a representative cohort of patients in the community • with the full spectrum of cardiovascular disease • followed for 5 years • Prevalence? • Dose-Response relationship? CCHSRD Seminar, NUIG, December 5th 2006
The Cohort • Randomised sample of 35 general practices in the West of Ireland. • 1,609 patients with established cardiovascular disease • Baseline data collected in 2000/2001 • Follow-up data collected in 2005/2006 CCHSRD Seminar, NUIG, December 5th 2006
Distribution of stratified random sample of general practices involved in the study CCHSRD Seminar, NUIG, December 5th 2006
MethodsStudy population and measurement of renal function • Diagnosis of CVD = angina, MI or coronary revascularisation • Renal Function Measure = Serum creatinine → eGFR • Estimated glomerular filtration rate (eGFR) calculated using: “MDRD equation” eGFR (ml/min/1.73m2) = 186 x (Serum creat. [mg/dL])–1.154 x (Age[yrs])–0.203 Gender: For women multiply by correction factor of 0.742 Race: For Afro-Caribbeans multiply by correction factor of 1.21 CCHSRD Seminar, NUIG, December 5th 2006
MethodsOutcomes • Primary Outcome = Death from any cause • Secondary outcome = Cardiovascular composite outcome • death from a cardiovascular cause • myocardial infarction • heart failure • peripheral vascular disease • stroke. CCHSRD Seminar, NUIG, December 5th 2006
MethodsAnalysis • Kaplan Meier Survival Analysis • Stepwise Cox proportional-hazards models [Forward selection (Wald criterion)] • eGFR as a categorical variable • ≥60 ml [n = 804] (Stage I & II) • 45-59 ml [n = 331] (Stage IIIa) • 30-44 ml [n = 98] (Stage IIIb) • <30 ml [n = 28] (Stage IV & V) • eGFR as a continuous variable CCHSRD Seminar, NUIG, December 5th 2006
Results CCHSRD Seminar, NUIG, December 5th 2006
ResultsStudy Sample CCHSRD Seminar, NUIG, December 5th 2006
ResultsBaseline Characteristics • Median follow-up = 2.90 years (SD 1.47) • Estimated GFR: Mean = 66 (17) ml/min/1.73m2 Range = 6-182 ml/min/1.73m2 CCHSRD Seminar, NUIG, December 5th 2006
ResultsDistribution of estimated GFR at baseline for the 1272 patients with a serum creatinine measurement 60ml/min/1.73m2 CCHSRD Seminar, NUIG, December 5th 2006
ResultsPrevalence of Chronic Kidney Disease • Estimated GFR ≥60 = 809/1272 (64%) • Estimated GFR <60 = 463/1272 (36%) (Stage III CKD or worse) • older and more likely to be female (variables in the MDRD equation) • higher prevalence of heart failure and previous CVD co-morbidity • less likely to be smoking or to have received PCI • more likely to be diabetic • higher mean SBP and total cholesterol • less likely to be receiving lipid lowering agents. CCHSRD Seminar, NUIG, December 5th 2006
ResultsPrimary OutcomeKaplan-Meier estimates for risk of all-cause mortality according to baseline estimated GFR CCHSRD Seminar, NUIG, December 5th 2006
ResultsSecondary OutcomeKaplan-Meier estimates for risk of cardiovascular composite end point according to baseline estimated GFR CCHSRD Seminar, NUIG, December 5th 2006
Results: Primary and Secondary Outcomes *This groups served as the reference group. ^The Cox regression model used in the above analysis adjusted for the variables of age, gender, social status, smoking status, salt intake, body mass index, systolic blood pressure, diastolic blood pressure, total cholesterol level, previous myocardial infarction, angina, heart failure, stroke, peripheral vascular disease, thromboembolic events, prior percutaneous transfemoral cardiac angiography, prior coronary artery bypass grafting, and diabetes mellitus.
Conclusions • Reduced estimated GFR appears to be a graded, independent and significant risk factor for mortality and new cardiovascular morbidity. • Dyslipidemia, hypertension, smoking, central obesity, and sedentary lifestyle + eGFR CCHSRD Seminar, NUIG, December 5th 2006
Acknowledgements • Health Research Board • ICGP Research and Education Foundation • Damian Griffen, Liam Connell, Eoin Clerkin and Mary Diver (UCHG, Mayo General, Sligo General and LetterKenny General Hospitals) • Data Collection: Ethna Shryane, Claire Hennigan, Michael O’Keefe • Our participating general practitioners and patients CCHSRD Seminar, NUIG, December 5th 2006
Questions? CCHSRD Seminar, NUIG, December 5th 2006
The stages of chronic kidney disease as outlined by the National Kidney Foundation Kidney Disease Outcomes Quality Initiative • StageClinical FeaturesGFR (mL/min/1.73 m2) • I* Kidney damage with normal or increased GFR 90 • II* Kidney damage with a mild decrease in GFR60-89 • III Moderate decrease in GFR30-59 • IV Severe decrease in GFR15-29 • V Kidney failure<15 or dialysis *Kidney damage = pathologic abnormalities or markers of disease present in the urine, blood or on imaging modalities. CCHSRD Seminar, NUIG, December 5th 2006
The Stages of chronic kidney disease (National Kidney Foundation Kidney Disease Outcomes Quality Initiative) *Kidney damage = pathologic abnormalities or markers of disease present in the urine, blood or on imaging modalities CCHSRD Seminar, NUIG, December 5th 2006
Summary Statistics for all-cause mortality according to baseline estimated GFR CCHSRD Seminar, NUIG, December 5th 2006
Summary Statistics for cardiovascular composite end point according to baseline estimated GFR *7 cases with incomplete data could not included in the analysis (Total: 1578 = 1571+7) CCHSRD Seminar, NUIG, December 5th 2006