For most people with CKD, the kidney is not what kills them — the heart is. Cardiovascular disease is the dominant cause of death across the CKD spectrum, and especially in the earlier stages, where patients are far more likely to die of a cardiovascular event than to ever reach dialysis. That single fact reframes CKD care: managing the kidney is, in large part, managing cardiovascular risk. But the cardiovascular disease of CKD is distinctive, the evidence is patchy because CKD patients were excluded from the trials, and the commonest error is not over-treatment but under-treatment.
The dominant killer, and a different disease
CKD is an independent and graded cardiovascular risk factor — the same heatmap that predicts kidney outcomes predicts cardiovascular ones, with risk rising as eGFR falls and albuminuria climbs. But the disease is not simply more atherosclerosis. Alongside accelerated coronary, cerebrovascular, and peripheral atherosclerosis sit a set of structural and electrical problems: left ventricular hypertrophy driven by pressure, volume, and anaemia; heart failure, the cardiorenal syndrome of the previous volume; arterial stiffness from the medial calcification of CKD-MBD; valvular calcification; and, prominently, sudden cardiac death, which becomes a leading mode of death in advanced and dialysis CKD. This breadth matters because interventions aimed only at atherosclerotic plaque — statins, for instance — address only part of the problem, which is part of why their benefit attenuates in advanced disease where calcification and sudden death dominate.
Why the risk is so high
The risk is the sum of two lists. The traditional factors — hypertension, diabetes, dyslipidaemia, smoking — are common in CKD and matter. But layered on top are the non-traditional, CKD-specific factors: the uraemic milieu with its retained toxins, chronic inflammation and oxidative stress, the mineral-bone disorder and vascular calcification of Chapter 8, anaemia, volume overload, and elevated FGF23 and phosphate. Because of this second list, standard cardiovascular risk calculators — built in non-CKD populations — systematically underestimate the risk, and the practical rule is to regard most CKD patients as high cardiovascular risk rather than relying on a score that was never calibrated for them.
The troponin trap
A specific diagnostic pitfall deserves attention. Troponin is frequently and chronically elevated in CKD, both because reduced renal clearance raises the baseline level and because subclinical myocardial injury is genuinely common. The trap is bidirectional: a clinician may dismiss a real acute coronary syndrome as 'just the CKD baseline,' or may over-react to a chronically elevated value in an asymptomatic patient. The resolution is to diagnose acute coronary syndrome from the trend — a significant rise and fall on serial high-sensitivity troponin, in the right clinical context — rather than from a single elevated value read against a non-CKD reference range. The baseline is elevated; the acute event is a change from it.
Statins, and the dialysis paradox
Lipid-lowering in CKD is the clearest illustration of why the evidence must be read carefully. The large SHARP trial of simvastatin with ezetimibe in CKD reduced atherosclerotic cardiovascular events, establishing the benefit of statin-based therapy in the CKD population. But the benefit is not uniform across that population: dedicated trials of starting a statin in haemodialysis patients — atorvastatin in diabetic dialysis patients, rosuvastatin in a broader dialysis population — were negative, showing no reduction in cardiovascular events. The likely explanation returns to the first section: in dialysis, the cardiovascular disease is increasingly calcification and sudden death rather than the lipid-driven atherosclerotic plaque that statins target. The resulting guidance is precise: initiate a statin (with or without ezetimibe) in non-dialysis CKD, particularly in adults over fifty; continue it if a patient is already taking one when they start dialysis; but do not routinely initiate a statin in a patient already on dialysis. And the approach is 'fire and forget' — a fixed regimen rather than titration to an LDL target.
The pillars are cardiovascular drugs too
It is easy to compartmentalise the progression-slowing pillars as 'kidney drugs,' but they are among the most effective cardiovascular interventions in CKD. SGLT2 inhibitors reduce heart-failure hospitalisation and cardiovascular death, benefits established in the heart-failure trials and carried into the CKD trials of Chapter 5. Blood-pressure control, on the SPRINT model of Chapter 4, reduces cardiovascular events, and RAAS blockade reduces them too, with GLP-1 agonists adding cardiovascular benefit in the diabetic. So the pillars do double duty, and the cardiovascular indication reinforces the renal one — another reason that, for most patients with progressive CKD, these drugs are not optional. Managing the traditional risk factors — glycaemia, lipids, blood pressure, smoking — completes the preventive package.
Antiplatelets, anticoagulation, and the hard decisions
Two areas are genuinely difficult because CKD raises both thrombotic and bleeding risk at once. Antiplatelet therapy is used for established atherosclerotic disease as secondary prevention, accepting the higher bleeding risk that CKD confers, while its role in primary prevention is uncertain. Anticoagulation for atrial fibrillation is harder still: CKD raises the risk of both stroke and bleeding, so the net benefit is finely balanced. In moderate CKD, dose-adjusted direct oral anticoagulants are generally preferred to warfarin, but in advanced CKD and dialysis the decision becomes genuinely uncertain — warfarin raises concerns about vascular calcification and calciphylaxis, while direct oral anticoagulants may accumulate, and the trial evidence is thin. These decisions are individualised, weighing the competing risks rather than applying a general-population rule. Sudden cardiac death, the other major threat, has frustratingly little proven prevention: managing electrolytes and avoiding QT-prolonging drugs help, but prophylactic defibrillators have not shown the benefit in dialysis that they do in the general heart-failure population.
Renalism: the error of under-treatment
If there is one behavioural lesson in this chapter, it is to beware renalism — the systematic under-treatment of cardiovascular disease in CKD patients out of misplaced caution. Fearing contrast nephropathy, bleeding, or futility, clinicians too often withhold from CKD patients the very interventions that would help them: coronary angiography and revascularisation, anticoagulation for atrial fibrillation, cardiac surgery, and even statins. The data are consistent that CKD patients are under-offered evidence-based cardiac care and that this under-treatment worsens their already high-risk outcomes. The corrective is not recklessness but proportion: contrast can be given with appropriate precautions for an indicated angiogram, anticoagulation can be considered on its merits, and a high-risk patient who would benefit from an intervention should not be denied it simply because they have CKD. The cardiovascular disease that kills them deserves to be treated.
Where the evidence is firm, and where it is absent
The firm parts: CKD is a major cardiovascular risk state, statins help in non-dialysis CKD, SGLT2 inhibitors reduce heart-failure and cardiovascular outcomes, and renalism causes harm. The conspicuous gaps come from a structural problem — CKD patients, especially advanced and dialysis patients, were routinely excluded from the landmark cardiovascular trials, so much of what we 'know' is extrapolated rather than tested. This is why the dialysis statin result surprised people, why anticoagulation in advanced CKD remains unresolved, and why sudden-cardiac-death prevention is weak. The honest stance is to apply the CKD-specific evidence where it exists — statins in non-dialysis disease, the pillars throughout — to extrapolate cautiously where it does not, and above all to resist the reflex to under-treat the leading cause of death in our patients.
