Chronic Kidney Disease and Cardiovascular Risk: Epidemiology, Mechanisms, and Prevention
The following are 10 points to remember about chronic kidney disease and cardiovascular risk:
1. In patients with chronic kidney disease, compared with the general population, cardiovascular disease is more frequent and severe, is often not recognized, and is often undertreated. Cardiac troponin concentrations are frequently raised in patients with chronic kidney disease, maybe because of reduced renal clearance, which makes their use as biomarkers for acute coronary syndromes problematic. Many physicians are reluctant to use coronary angiography in patients with chronic kidney disease, especially in those with estimated glomerular filtration rate stage 3–5, owing to the risk of renal toxic effects from the iodine contrast media.
2. Patients with chronic kidney disease should be viewed among the highest-risk groups for cardiovascular events and disease, and require special clinical attention at an individual patient level, in the development of guidelines, and in the defining of research priorities. Increased cardiovascular risk in individuals with chronic kidney disease is due partly to the high prevalence of traditional risk factors.
3. Cardiovascular mortality was about twice as high in patients with stage 3 chronic kidney disease (estimated glomerular filtration rate 30-59 ml/min per 1.73 m2) and three times higher at stage 4 (15-29 ml/min per 1.73 m2) than that in individuals with normal kidney function. A wide variety of specific cardiovascular diseases have been associated with estimated impaired kidney function. Risk of heart failure is roughly doubled in patients with estimated glomerular filtration rates lower than 60 ml/min per 1.73 m2 compared to that in people with preserved estimated glomerular filtration rates. The risk is similarly increased for stroke, peripheral artery disease, coronary heart disease, and atrial fibrillation. The associations between chronic kidney disease and cardiovascular disease are largely irrespective of age, sex, and ethnic origin. Data have been reported for US, European, Taiwanese, and South Korean general-population cohorts.
4. Life expectancy was substantially reduced for patients with impaired kidney function in a Canadian cohort. Patients ages 30 years with estimated glomerular filtration rate stage 3B (30-44 ml/min per 1.73 m2) or 4 (15-29 ml/min per 1.73 m2) had reductions in life expectancy of approximately 17 or 25 years, respectively, compared to individuals with normal kidney function.
5. In patients with mild to moderate chronic kidney disease (stages 3A and 3B), the incidence of cardiovascular mortality is much higher than the incidence of kidney failure. Only in patients with severely impaired kidney function (stage 4) does the risk of kidney failure surpass that of cardiovascular events.
6. Hypertension is a well-known and strong risk factor for development of chronic kidney disease. A target blood pressure of <140/90 mm Hg is deemed appropriate to prevent cardiovascular events in patients with chronic kidney disease; a lower target blood pressure of <130/80 mm Hg is recommended only in patients with increased albuminuria (>30 mg/g). Any of the various classes of antihypertensive agents can be effectively used in patients with chronic kidney disease, but renin-angiotensin-aldosterone system (RAAS) inhibitors are the first-line agents. The benefits of RAAS inhibitors go beyond those expected from the lowering of blood pressure alone, and are largely explained by their albuminuria-lowering effects.
7. Patients with chronic kidney disease are generally volume overloaded, and diuretic therapy is often indicated. High-dose loop diuretics, rather than thiazide diuretics, become necessary to control fluid retention and accompanying hypertension if kidney function declines. Diuretics increase the efficacy of RAAS inhibitors to lower albuminuria, which can result in additional renoprotection.
8. Histologically, left ventricular hypertrophy in chronic kidney disease is characterized by myocardial fibrosis that is thought to impair contractility. The high prevalence of left ventricular hypertrophy, with its associated risk of cardiac rhythm disturbances, could at least partly explain why the prevalence of sudden cardiac death is increased in people with chronic kidney disease. In the general population, sudden cardiac death accounts for roughly one death per 1,000 person-years and for 6-13% of all deaths, whereas among individuals with kidney failure, the rates are 59 deaths per 1,000 person-years and 26% of total mortality. Other factors that raise cardiovascular risk in patients with chronic kidney disease include increased activity of the renin–angiotensin system and sympathetic nerve activity in chronic kidney disease.
9. A review of seven intervention studies that included 6,250 individuals without chronic kidney disease showed that dietary sodium restriction was associated with a significant 20% reduction in cardiovascular events during follow-up. In individuals with chronic kidney disease, sodium restriction might enhance the effects of blockers of the RAAS on albuminuria and renal function.
10. A systematic review of 13 randomized, controlled trials of weight loss in overweight or obese patients with chronic kidney disease revealed that intentional weight loss was associated with decreases in albuminuria that were independent of decreases in blood pressure.
This review highlights the importance of managing cardiovascular risk among patients with renal disease. Further research is warranted to improve early identification and treatment of cardiovascular disease among this high-risk population.
Clinical Topics: Acute Coronary Syndromes, Heart Failure and Cardiomyopathies, Prevention, Vascular Medicine, Atherosclerotic Disease (CAD/PAD), ACS and Cardiac Biomarkers, Acute Heart Failure, Heart Failure and Cardiac Biomarkers, Hypertension
Keywords: Stroke, Acute Coronary Syndrome, Weight Loss, Diuretics, Peripheral Arterial Disease, Risk Factors, Creatinine, Sodium Potassium Chloride Symporter Inhibitors, Sodium Chloride, Dietary, Biological Markers, Heart Failure, Obesity, Glomerular Filtration Rate, Hypertension, Renal Insufficiency, Chronic, Troponin
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