Chronic Kidney Disease and Risk of Major Cardiovascular Disease
Chronic Kidney Disease and Risk of Major Cardiovascular Disease
Objective To quantify associations of chronic kidney disease stages with major cardiovascular disease and non-vascular mortality in the general adult population.
Design Prospective population based cohort study.
Setting Reykjavik, Iceland.
Participants 16 958 people aged 33-81 years without manifest vascular disease and with available information on stage of chronic kidney disease (defined by both estimated glomerular filtration rate and urinary protein) at study entry.
Main outcome measures Hazard ratios for time to major coronary heart disease outcomes and mortality.
Results 1210 (7%) of participants had chronic kidney disease at entry. During a median follow-up of 24 years, 4010 coronary heart disease outcomes, 559 deaths from stroke, and 3875 deaths from non-vascular causes were recorded. Compared with the reference group (estimated glomerular filtration rate 75-89 ml/min/1.73 m and no proteinuria), people with lower renal function within the normal range of glomerular filtration rate did not have significantly higher risk of coronary heart disease. By contrast, in 1210 (7%) participants with chronic kidney disease at entry, hazard ratios for coronary heart disease, adjusted for several conventional cardiovascular risk factors, were 1.55 (95% confidence interval 1.02 to 2.35) for stage 1, 1.72 (1.30 to 2.24) for stage 2, 1.39 (1.22 to 1.58) for stage 3a, 1.90 (1.22 to 2.96) for stage 3b, and 4.29 (1.78 to 10.32) for stage 4. Information on chronic kidney disease increased discrimination and reclassification indices for coronary heart disease when added to conventional risk factors (P<0.01). The incremental gain provided by chronic kidney disease was lower than that provided by diabetes or smoking (C index increases of 0.0015, 0.0024, and 0.0124 respectively). Hazard ratios with chronic kidney disease were 0.97 (0.82 to 1.15) for cancer mortality and 1.26 (1.07 to 1.50) for other non-vascular mortality.
Conclusions In people without manifest vascular disease, even the earliest stages of chronic kidney disease are associated with excess risk of subsequent coronary heart disease. Assessment of chronic kidney disease in addition to conventional risk factors modestly improves prediction of risk for coronary heart disease in this population. Further studies are needed to investigate associations between chronic kidney disease and non-vascular mortality from causes other than cancer.
End stage renal failure is known to be associated with striking excesses of cardiovascular and all cause mortality. Strong associations have also been reported between non-dialysis dependent chronic kidney disease and such outcomes in patients with ischaemic cardiovascular diseases, heart failure, and high blood pressure. Such observations have led to recommendations by scientific and professional bodies that patients with manifest cardiovascular disease should be screened for evidence of kidney disease and that patients with chronic kidney disease should be regarded as at very high risk of coronary heart disease. In the general adult population, however, chronic kidney disease often goes undiagnosed because it is largely asymptomatic. Several population based prospective studies have reported on associations between renal function and vascular disease. However, many such studies have lacked concomitant assessment of estimated glomerular filtration rate and urinary protein status or involved less than 10 years of follow-up (the time horizon used in most clinical cardiovascular risk scores), omitted measures of discrimination or reclassification of risk to help in judging the incremental predictive value of assessing chronic kidney disease, or involved some combination of these limitations. Hence, determining the potential value of assessment of chronic kidney disease in population-wide cardiovascular disease screening programmes, such as the National Health Service health check in the United Kingdom, has been difficult.
We report on the incremental value of assessment of chronic kidney disease for prediction of risk for coronary heart disease in a population based prospective study of people without manifest vascular disease who have been monitored, on average, for almost a quarter of a century. To assist in interpretation, we have compared the predictive ability of chronic kidney disease with that of smoking and diabetes.
Abstract
Objective To quantify associations of chronic kidney disease stages with major cardiovascular disease and non-vascular mortality in the general adult population.
Design Prospective population based cohort study.
Setting Reykjavik, Iceland.
Participants 16 958 people aged 33-81 years without manifest vascular disease and with available information on stage of chronic kidney disease (defined by both estimated glomerular filtration rate and urinary protein) at study entry.
Main outcome measures Hazard ratios for time to major coronary heart disease outcomes and mortality.
Results 1210 (7%) of participants had chronic kidney disease at entry. During a median follow-up of 24 years, 4010 coronary heart disease outcomes, 559 deaths from stroke, and 3875 deaths from non-vascular causes were recorded. Compared with the reference group (estimated glomerular filtration rate 75-89 ml/min/1.73 m and no proteinuria), people with lower renal function within the normal range of glomerular filtration rate did not have significantly higher risk of coronary heart disease. By contrast, in 1210 (7%) participants with chronic kidney disease at entry, hazard ratios for coronary heart disease, adjusted for several conventional cardiovascular risk factors, were 1.55 (95% confidence interval 1.02 to 2.35) for stage 1, 1.72 (1.30 to 2.24) for stage 2, 1.39 (1.22 to 1.58) for stage 3a, 1.90 (1.22 to 2.96) for stage 3b, and 4.29 (1.78 to 10.32) for stage 4. Information on chronic kidney disease increased discrimination and reclassification indices for coronary heart disease when added to conventional risk factors (P<0.01). The incremental gain provided by chronic kidney disease was lower than that provided by diabetes or smoking (C index increases of 0.0015, 0.0024, and 0.0124 respectively). Hazard ratios with chronic kidney disease were 0.97 (0.82 to 1.15) for cancer mortality and 1.26 (1.07 to 1.50) for other non-vascular mortality.
Conclusions In people without manifest vascular disease, even the earliest stages of chronic kidney disease are associated with excess risk of subsequent coronary heart disease. Assessment of chronic kidney disease in addition to conventional risk factors modestly improves prediction of risk for coronary heart disease in this population. Further studies are needed to investigate associations between chronic kidney disease and non-vascular mortality from causes other than cancer.
Introduction
End stage renal failure is known to be associated with striking excesses of cardiovascular and all cause mortality. Strong associations have also been reported between non-dialysis dependent chronic kidney disease and such outcomes in patients with ischaemic cardiovascular diseases, heart failure, and high blood pressure. Such observations have led to recommendations by scientific and professional bodies that patients with manifest cardiovascular disease should be screened for evidence of kidney disease and that patients with chronic kidney disease should be regarded as at very high risk of coronary heart disease. In the general adult population, however, chronic kidney disease often goes undiagnosed because it is largely asymptomatic. Several population based prospective studies have reported on associations between renal function and vascular disease. However, many such studies have lacked concomitant assessment of estimated glomerular filtration rate and urinary protein status or involved less than 10 years of follow-up (the time horizon used in most clinical cardiovascular risk scores), omitted measures of discrimination or reclassification of risk to help in judging the incremental predictive value of assessing chronic kidney disease, or involved some combination of these limitations. Hence, determining the potential value of assessment of chronic kidney disease in population-wide cardiovascular disease screening programmes, such as the National Health Service health check in the United Kingdom, has been difficult.
We report on the incremental value of assessment of chronic kidney disease for prediction of risk for coronary heart disease in a population based prospective study of people without manifest vascular disease who have been monitored, on average, for almost a quarter of a century. To assist in interpretation, we have compared the predictive ability of chronic kidney disease with that of smoking and diabetes.
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