Mild Renal Dysfunction Associated With Incident CAD in Young Males
Mild Renal Dysfunction Associated With Incident CAD in Young Males
Aims: Although impaired renal function is associated with adverse cardiovascular outcomes, it is unknown whether this association exists in young, healthy adults with normal or mildly impaired renal dysfunction.
Methods and Results: We calculated the baseline creatinine clearance of young males without antecedent diabetes mellitus, coronary artery disease (CAD), or renal dysfunction, and examined their subsequent diagnosis of CAD, defined as coronary artery diameter stenosis of at least 50% and/or myocardial infarction. The 23 964 males, 32.5 ± 5.9 years old, had a baseline estimated creatinine clearance of 107.9 ± 0.6 mL min per 1.73 m (60–150 mL min per 1.73 m). During a mean follow-up of 3.5 ± 1.9 years, 77 subjects were diagnosed with CAD. After age adjustment, there was a progressive increase in the risk for CAD as the estimated creatinine clearance decreased [hazard ratio (HR) 4.77, 95% confidence interval 3.22–7.06, P < 0.001 for comparison between the fifth and first quintiles]. This association also persisted after further adjustments for conventional and ancillary risk factors for CAD (HR 2.10, 95% confidence interval 1.40–3.14, P < 0.001).
Conclusion: Reduced renal function in the normal to mildly impaired range is independently associated with increased risk for CAD among young, healthy males.
Chronic renal failure is a well-established risk factor for cardiovascular morbidity and mortality. Most prior studies that examined the relationship between renal function and cardiovascular outcomes relied on serum creatinine, an unreliable proxy of renal function. Indeed, a significant proportion of patients with serum creatinine levels slightly above the upper limit of the normal range or even within the normal range have impaired renal function, often even significant renal dysfunction, thus compromising the validity of the prior studies.
More recently, renal function has been assessed using equations estimating the glomerular filtration rate. Several studies have clearly demonstrated that reduced values of glomerular filtration rate that are even within the mildly impaired or normal range are associated with worse cardiovascular outcomes among a wide spectrum of patients with established cardiovascular conditions, including asymptomatic and symptomatic heart failure, acute myocardial infarction, and surgical or percutaneous revascularization. There are also data that a glomerular filtration rate <60 mL min per 1.73 m is a risk factor for both new and recurrent cardiovascular disease in the general population and in people at increased risk for cardiovascular disease. More recent studies demonstrated a correlation between elevated levels of cystatin C, a serum measure of renal function, and an increased risk of cardiovascular events and death among elderly outpatients without acute cardiovascular conditions. The linear association of cystatin C with the risk of death or cardiovascular disease among elderly subjects with renal function within the normal range (glomerular filtration rate of at least 60 mL min per 1.73 m) suggests that differences in renal function within the normal range impact on cardiovascular outcomes. However, similar to most other studies, this study included only elderly patients, many of whom had different co-morbidities that may be associated with renal dysfunction, such as diabetes mellitus and heart failure. There are no firm data hitherto regarding a possible correlation between differences in renal function within the normal or mildly impaired range and cardiovascular outcomes among young, healthy adults.
The aim of the current study was to test the hypothesis that mild renal dysfunction is associated with incident coronary artery disease (CAD) in otherwise healthy, young males enrolled in the Metabolic, Lifestyle and Nutrition Assessment in Young adults (MELANY) study.
Aims: Although impaired renal function is associated with adverse cardiovascular outcomes, it is unknown whether this association exists in young, healthy adults with normal or mildly impaired renal dysfunction.
Methods and Results: We calculated the baseline creatinine clearance of young males without antecedent diabetes mellitus, coronary artery disease (CAD), or renal dysfunction, and examined their subsequent diagnosis of CAD, defined as coronary artery diameter stenosis of at least 50% and/or myocardial infarction. The 23 964 males, 32.5 ± 5.9 years old, had a baseline estimated creatinine clearance of 107.9 ± 0.6 mL min per 1.73 m (60–150 mL min per 1.73 m). During a mean follow-up of 3.5 ± 1.9 years, 77 subjects were diagnosed with CAD. After age adjustment, there was a progressive increase in the risk for CAD as the estimated creatinine clearance decreased [hazard ratio (HR) 4.77, 95% confidence interval 3.22–7.06, P < 0.001 for comparison between the fifth and first quintiles]. This association also persisted after further adjustments for conventional and ancillary risk factors for CAD (HR 2.10, 95% confidence interval 1.40–3.14, P < 0.001).
Conclusion: Reduced renal function in the normal to mildly impaired range is independently associated with increased risk for CAD among young, healthy males.
Chronic renal failure is a well-established risk factor for cardiovascular morbidity and mortality. Most prior studies that examined the relationship between renal function and cardiovascular outcomes relied on serum creatinine, an unreliable proxy of renal function. Indeed, a significant proportion of patients with serum creatinine levels slightly above the upper limit of the normal range or even within the normal range have impaired renal function, often even significant renal dysfunction, thus compromising the validity of the prior studies.
More recently, renal function has been assessed using equations estimating the glomerular filtration rate. Several studies have clearly demonstrated that reduced values of glomerular filtration rate that are even within the mildly impaired or normal range are associated with worse cardiovascular outcomes among a wide spectrum of patients with established cardiovascular conditions, including asymptomatic and symptomatic heart failure, acute myocardial infarction, and surgical or percutaneous revascularization. There are also data that a glomerular filtration rate <60 mL min per 1.73 m is a risk factor for both new and recurrent cardiovascular disease in the general population and in people at increased risk for cardiovascular disease. More recent studies demonstrated a correlation between elevated levels of cystatin C, a serum measure of renal function, and an increased risk of cardiovascular events and death among elderly outpatients without acute cardiovascular conditions. The linear association of cystatin C with the risk of death or cardiovascular disease among elderly subjects with renal function within the normal range (glomerular filtration rate of at least 60 mL min per 1.73 m) suggests that differences in renal function within the normal range impact on cardiovascular outcomes. However, similar to most other studies, this study included only elderly patients, many of whom had different co-morbidities that may be associated with renal dysfunction, such as diabetes mellitus and heart failure. There are no firm data hitherto regarding a possible correlation between differences in renal function within the normal or mildly impaired range and cardiovascular outcomes among young, healthy adults.
The aim of the current study was to test the hypothesis that mild renal dysfunction is associated with incident coronary artery disease (CAD) in otherwise healthy, young males enrolled in the Metabolic, Lifestyle and Nutrition Assessment in Young adults (MELANY) study.
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