CKD Linked to Elevated Cardiovascular Risk Even at Early Stages

Cardiovascular complications continued to define outcomes for people living with chronic kidney disease (CKD), even when kidney impairment was mild, according to a large systematic review that underscored how early cardiovascular risk emerged and intensified as renal function declined.

A systematic review reveals that cardiovascular risks emerge early in chronic kidney disease, highlighting the need for tailored management strategies. | Image credit: Fotolia_166490197_Subscription_XXL - stock.adobe.com

The review, published in Medicine, synthesized evidence from 7 observational and cohort studies to clarify how CKD contributed to cardiovascular morbidity and mortality and to examine why standard cardiovascular prevention strategies often fell short in this population.1 Investigators reported that across diverse settings and CKD stages, people with CKD consistently faced higher rates of coronary heart disease, stroke, and cardiovascular death than individuals without kidney disease.

CKD affects an estimated 10% of the global population and remains one of the strongest nontraditional risk factors for cardiovascular disease (CVD).2 Although clinicians widely recognize that advanced CKD confers cardiovascular risk, uncertainty persists about how early that risk begins and how much it is driven by kidney-specific mechanisms rather than traditional risk factors alone.1

The authors noted that cardiovascular disease remains the leading cause of death among people with CKD and that patients with reduced kidney function were often excluded from cardiovascular trials, limiting the applicability of guideline-based interventions. The review sought to consolidate existing data to better define the scope of risk and identify gaps in management strategies.

The systematic review followed PRISMA guidelines and included 7 studies published through December 2024. Study designs comprised prospective cohorts, cross-sectional analyses, and population-based cohorts. In total, the studies included more than 107,000 participants spanning a wide range of kidney function, from early CKD to dialysis-dependent disease.

Participants varied by age, sex, and geographic region. Several studies included predominantly middle-aged or older adults, reflecting the demographics of CKD populations seen in routine care. CKD staging was primarily defined by estimated glomerular filtration rate (eGFR), with many cohorts including individuals with stage 3 disease or worse.

Across studies, CKD was consistently associated with elevated cardiovascular risk, even after adjustment for traditional factors such as hypertension, diabetes, and dyslipidemia. In multiple cohorts, individuals with CKD experienced a 1.4- to 2-fold higher risk of cardiovascular events or death compared with those without CKD.

Importantly, several studies demonstrated that cardiovascular risk increased even in early stages of kidney disease. In a large population-based cohort, mild reductions in eGFR were associated with a roughly 50% higher risk of coronary heart disease and cardiovascular mortality. Another community-based study showed that people with CKD had a 4-fold higher estimated 10-year cardiovascular risk than those without CKD.

Traditional cardiovascular risk factors were highly prevalent among people with CKD. Hypertension, diabetes, obesity, and dyslipidemia appeared frequently across cohorts and intensified as kidney function worsened. However, the review emphasized that nontraditional CKD-specific mechanisms—including chronic inflammation, oxidative stress, uremic toxins, mineral metabolism disturbances, and anemia—likely amplified cardiovascular risk beyond what traditional models captured.

One prospective study highlighted the prognostic significance of coronary microvascular dysfunction, showing that people with CKD and impaired coronary flow reserve had more than twice the risk of cardiac death compared with those with preserved flow.

Clinical and Managed Care Implications

The authors emphasized that standard cardiovascular interventions often proved less effective in people with CKD due to disease-specific pathophysiology and competing risks. While antihypertensive agents, statins, and glucose-lowering therapies remained foundational, treatment targets were frequently difficult to achieve, particularly in advanced CKD.

Newer therapies, including sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists, showed promise for improving both cardiovascular and renal outcomes, but long-term CKD-specific data remained limited. The authors called for earlier identification of cardiovascular risk in CKD and more individualized, multimodal management approaches.

As the authors noted, “Addressing cardiovascular risk in CKD patients is crucial to reducing mortality and improving their overall quality of life.”

The review had several limitations. Most included studies were observational, limiting causal inference. Substantial heterogeneity existed in CKD definitions, cardiovascular outcomes, and follow-up durations, which complicated direct comparisons. Some studies lacked detailed stratification by CKD stage or did not report fully adjusted risk estimates. Additionally, the exclusion of non-English publications raised the possibility of language bias.

Despite these limitations, the review reinforced that cardiovascular risk in CKD began early and escalated alongside declining kidney function. The findings highlighted the need for CKD-inclusive cardiovascular trials, improved risk stratification tools, and earlier intervention strategies aimed at both traditional and kidney-specific mechanisms.

References

1. Hassan MB, Siddique S, Maheshwari SK, et al. Chronic kidney disease and cardiovascular risk: Pathophysiology and interventional approaches – systematic review. Medicine (Baltimore). 2025;104(49):e46189. doi:10.1097/MD.0000000000046189

2. Levey AS, Atkins R, Coresh J, et al. Chronic kidney disease as a global public health problem: approaches and initiatives - a position statement from kidney disease improving global outcomes. Kidney Int. 2007;72:247-259. doi:10.1038/sj.ki.5002343