- Heart disease is the leading cause of death in the United States
- Chronic kidney disease (CKD) is a leading cause of cardiovascular disease (CVD)
- Heart disease is likewise a leading factor in the development of CKD
- Persons with end-stage renal disease, on dialysis, are more likely to die from heart disease than kidney failure
- CKD and CVD share a number of risk factors, including type 2 diabetes and hypertension
- Heart health should be an essential element of kidney healthcare (and vice versa)
CKD and CVD are almost inseparably interwoven. They share common precipitators, such as diabetes and hypertension, so a person diagnosed with CKD is more than likely to have heart disease, and the reverse is also true.
An excess of glucose in the bloodstream causes damage to blood vessels and kidneys. As the kidneys begin to lose function, the heart must pump harder to get more blood to the kidneys for cleansing. This results in high blood pressure with even more damage to arteries, kidneys and the heart itself—a truly vicious cycle. Because of this close relationship, patients being treated for diabetes and/or high blood pressure must also be tested for indications of kidney disease.
Fortunately, what’s good for one is good for the other. A heart-healthy regimen (diet, exercise, smoking cessation, etc.) will pay dividends in kidney disease management, helping to slow CKD’s progression.
This is important, because:
“Cardiovascular disease is ... the first cause of death in patients with end-stage renal disease on hemodialysis (HD). In this population, mortality due to CVD is 20 times higher than in the general population and the majority of maintenance HD patients have CVD.”Cardiovascular Disease in Chronic Kidney Disease: Pathophysiological Insights and Therapeutic Options.2
Click the title to read the entire paper. Meanwhile, here are some (edited) highlights.
- Traditional cardiovascular risk factors are highly prevalent in patients with CKD, and their contribution to atherosclerotic vascular disease is particularly important in earlier CKD stages. Among others, hypertension, insulin resistance/diabetes, dyslipidemia, and smoking contribute not only to atherosclerotic cardiovascular and cerebrovascular sequelae but also to CKD progression because of their effect on large and smaller kidney vessels.
- The ADVANCE trial (“Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation”) demonstrated ... that intensive glucose control compared with standard therapy leads to a reduction in the combined outcome of major macrovascular and microvascular events, but this effect was mainly driven by a reduction in nephropathy with no significant effect on macrovascular events; the ACCORD trial (“Action to Control Cardiovascular Risk in Diabetes”) was not able to demonstrate that treatment targeting nearly normal glycemic control reduces the risk of cardiovascular events.
- Cardiovascular calcifications are markedly accelerated in patients with CKD, and even children with advanced CKD frequently exhibit vascular calcifications. The histological prevalence of vascular calcifications in radial arteries was 45-fold greater in patients with CKD compared with those without CKD. In addition to CKD, several common comorbidities, in particular diabetes, further enhance the progression of calcification.
- There is an epidemiological collinearity of the prevalence and incidence of CKD with aortic and mitral valve disease. Early CKD stages 1 to 3 are associated with enhanced calcifications of valves and coronary arteries. Heart valve calcification occurs in stage 5 CKD in up to 88% to 99% of patients, increasing from 40% of patients in CKD stage 3, and the final destruction of valves occurs at a 10-fold higher rate in patients with CKD compared with patients without CKD. Valvular disease in patients with CKD is accelerated by comorbidities like diabetes, arterial hypertension, hyperlipidemia [and] anemia.
Regarding treatment of vascular disease in patients with CKD:
- Control of traditional risk factors as well as antiplatelet therapy are cornerstones to reduce cardiovascular risk. As such, current guidelines recommend to lower systolic blood pressure to a range of 130 to 139 mm Hg in patients with diabetic or nondiabetic CKD, and renin-angiotensin-aldosterone inhibitors are first-line agents in CKD. Given the only moderate effect of glucose control on macrovascular events, hemoglobin A1c targets should be individualized, and side effects such as hypoglycemia should be avoided, in particular in CKD, because hypoglycemic episodes are associated with an increase in mortality in this group of patients.
- Data from large cardiovascular outcome trials with glucose-lowering sodium-glucose cotransporter 2 (SGLT2) inhibitors or GLP-1 receptor agonists have shown a significant reduction in cardiovascular events in patients with type 2 diabetes at high cardiovascular risk. Thus, various guidelines recommend treatment with these agents in CKD and non-CKD patients with CVD or multiple cardiovascular risk factors.
The authors also note that more than two-thirds of mortalities in advanced CKD stages are the result of sudden cardiac death.
- Sudden cardiac death refers to the unexpected natural death from a cardiac cause within 1 hour after onset of symptoms in a person who has no lethal underlying disease. The rate of sudden cardiac death is 59 deaths in 1,000 patient-years in the CKD stage 5 population, whereas it is 1 death in 1,000 patient-years in the general population.
- Dialysis itself is a risk factor for sudden cardiac death, with the highest risk of sudden cardiac death within the first 12 hours after dialysis and after a long dialysis-free interval. Potential mechanisms include volume and sudden electrolyte shifts after dialysis as well as volume overload and electrolyte disturbance. Accordingly, patients with peritoneal dialysis seem to exhibit a lower risk for sudden cardiac death.
- Although CKD is one of the most common comorbidities for patients with CVD, few specific treatment options are available for the high-risk population of patients with advanced CKD. Finding a balance between the optimization of clinical outcomes in CKD and CVD still requires validation in large prospective, multicenter clinical studies.
- SGLT2 inhibitors, currently used to treat patients with type 2 diabetes, have shown unprecedented cardiovascular as well as kidney protective effects.