Lifestyle and diet
Few data are available regarding the independent contribution of diet and lifestyle factors on the acceleration of CVD in patients with CKD. However, given the clustering of risk factors associated with obesity and type 2 diabetes, one would expect that a sedentary lifestyle and/or poor dietary habits, including an excessive intake of sugars, simple carbohydrates, and saturated fats, would be common among patients with, at a minimum, early diabetic CKD. Weight reduction has been shown to notably improve blood glucose control and, in some cases, result in the apparent resolution of diabetes as it is currently defined. Moreover, exercise training programmes can improve the conventional cardiac risk profile of renal transplant recipients.w3–5 Although there have been no prospective, comparative studies of diet and lifestyle changes on CVD outcomes in patients with CKD, normalisation of body weight and fat stores, reduction in sodium intake, and regular aerobic exercise would be expected to have a salutary impact on this escalating patient population (table 1). Given the expected higher rates of novel risk factors including endothelial dysfunction, oxidative stress, and inflammation, intensive lifestyle modification, including dietary changes and regular aerobic exercise, may reduce the incidence of CVD in this population.
Table 1 Primary and secondary cardiovascular disease prevention strategies for patients with chronic kidney disease
The renin–angiotensin system (RAS) and sympathetic nervous system are aberrantly activated, resulting in increased afterload, left ventricular enlargement, greater myocardial oxygen consumption, and augmented sheer stress at the endothelial level in patients with CKD. Opportunities for modulation of the RAS within the vascular tree occur at several points (fig 2). Additionally, many CKD patients with hypertension develop left ventricular hypertrophy, resulting in an increased myocardial mass to endothelial surface area, and an unfavourable myocardial oxygen supply and demand relation. Hyperactivation of the RAS leads to expression of oxidised low density lipoprotein receptors and acceleration of atherosclerosis (fig 3). As eGFR declines, systemic blood pressure rises causing greater sheer stress, increased risk of plaque rupture, and episodic coronary occlusion. Consequently, blood pressure control to a target systolic blood pressure < 130 mm Hg (ideally < 120 mm Hg) is currently recommended (table 1).
Figure 2 Angiotensinogen is secreted by the liver and is cleaved by renin, which is secreted into the lumen of renal afferent arterioles by juxtaglomerular cells. Angiotensin I is then converted to angiotensin II by angiotensin converting enzyme, primarily (more ...)
Figure 3 The renin–angiotensin system, creating the formation of angiotensin II, directly upregulates oxidised low density lipoprotein receptors on the endothelium and accelerates the progression of coronary atherosclerosis. EC, endothelial cell; (more ...)
Over 40% of end stage renal disease (ESRD) is secondary to diabetic nephrosclerosis,w6
and 48–57% of patients with diabetes mellitus (DM) have overt diabetic nephropathy.1
Patients with diabetes have significantly raised concentrations of serum insulin, a potent growth factor for atherosclerosis, in addition to a dyslipidaemic state. The epidemic of diabetes so measurably impacts CVD that the most recent National Cholesterol Education Program adult treatment panel guidelines listed DM as a CVD equivalent, and recommend treating afflicted patients accordingly.w7
In those with excess adiposity and type 2 diabetes, weight reduction is the intervention of choice to improve or resolve the diabetic condition. Optimal glycaemic control (glycohaemoglobin < 7%) has been shown to reduce microvascular events (retinopathy) and, along with blood pressure lowering, decrease the incidence of macrovascular events (myocardial infarction, stroke, and CVD death) in patients with type 1 or type 2 diabetes.
Dyslipidaemias occur in up to 67% of CKD patients.w8 This patient population often demonstrates diminished concentrations of cardioprotective high density lipoprotein cholesterol (HDL-C), and atherogenic increases in triglycerides and low density lipoprotein cholesterol (LDL-C). In particular, CKD patients have heightened concentrations of apolipoproteins AIV and B48. Furthermore, uraemic stress results in increased concentrations of oxidised LDL-C, a highly reactive and atherogenic species. Thus, it appears that hyperactivation of the RAS, raised insulin concentrations, and the dyslipidaemia of CKD work in concert to advance atherosclerosis at faster rates than in those with preserved renal function. Current guidelines support the lipid targets given in table 1.
ACE: angiotensin converting enzyme
CABG: coronary artery bypass grafting
CKD: chronic kidney disease
Cr: serum creatinine
CRP: C reactive protein
CVD: cardiovascular disease
DM: diabetes mellitus
eGFR: estimated glomerular filtration rate
ESRD: end stage renal disease
HDL-C: high density lipoprotein cholesterol
LDL-C: low density lipoprotein cholesterol
PCI: percutaneous coronary intervention
RAS: renin–angiotensin system
RRT: renal replacement therapy
TGF-β1: transforming growth factor beta 1