Addressing Underrepresented Factors in Cardiovascular Mortality Trends Among Chronic Kidney Disease Patients: A Call for Comprehensive Intervention Strategies

I read with great interest the comprehensive retrospective analysis by Ahmad et al. examining cardiovascular mortality trends in chronic kidney disease (CKD) patients from 1999 to 2020 [1]. While the authors excellently document demographic disparities and temporal patterns in cardiovascular mortality, their work highlights several critical gaps that warrant further discussion, particularly regarding the underutilization of evidence-based interventions and the impact of emerging therapeutic paradigms on cardiovascular outcomes in CKD patients.

The study period (1999−2020) captures a transformative era in CKD management, yet the authors do not adequately address how the introduction of novel therapies may explain certain mortality trends. The 2024 KDIGO guidelines now emphasize SGLT2 inhibitors as cornerstone therapy, showing remarkable cardiovascular benefits in CKD populations [2]. Recent meta-analyses demonstrate that SGLT2 inhibitors reduce major adverse cardiovascular events by 9%−14% in CKD patients, with particularly strong effects on heart failure hospitalization and cardiovascular death [3].

Similarly, the emergence of non-steroidal mineralocorticoid receptor antagonists (MRAs) like finerenone has revolutionized CKD-cardiovascular care. The pooled FIDELITY analysis demonstrated a 14% reduction in cardiovascular death, myocardial infarction, stroke, and heart failure hospitalization, with a 23% reduction in CKD progression [4]. These therapeutic advances, introduced toward the end of the study period, likely contributed to the stabilization of mortality rates observed by Ahmad et al.

The significant racial and geographic disparities documented by the authors reflect deeper healthcare access issues that extend beyond demographic risk factors. Research demonstrates that up to 98% of people with kidney failure in low-income regions cannot access kidney replacement therapy, compared to 30% in high-income countries [5]. Within the United States, these disparities manifest as differential access to nephrology care, with rural and minority populations experiencing delays in specialist referral and reduced access to evidence-based therapies [6].

The authors' observation that non-metropolitan areas exhibited higher age-adjusted mortality rates (8.6 vs. 8.1 per 100 000) underscores the critical role of healthcare infrastructure in cardiovascular outcomes. Studies show that less than one-third of community healthcare settings in resource-limited areas can access essential diagnostics for CKD monitoring, further contributing to delayed intervention and poor outcomes [5].

The study period concludes in 2020, capturing the early COVID-19 pandemic impact. Recent evidence demonstrates that COVID-19 significantly amplifies cardiovascular risk in CKD patients, with a twofold increased risk of cardiovascular death within 30 days and a 64% increased risk overall compared to non-CKD patients. This pandemic effect may have influenced the mortality trends observed in 2020 and represents an important confounding factor not addressed in the analysis.

The stable mortality trends observed by Ahmad et al. contrast sharply with the declining cardiovascular mortality in the general population, suggesting that CKD patients are not benefiting equally from advances in cardiovascular care. This disparity emphasizes several urgent priorities:

First, implementation science research is needed to optimize the delivery of evidence-based therapies. Studies show that combination therapy with SGLT2 inhibitors, MRAs, and RAAS inhibitors can provide additive cardiovascular protection, yet uptake remains suboptimal.

Second, targeted interventions for high-risk populations identified by the authors are essential. The significantly higher mortality rates in Non-Hispanic Black or African American patients (15.37 per 100 000) demand culturally adapted cardiovascular risk reduction programs and improved access to specialty care.

Third, the healthcare system must address the fundamental infrastructure gaps that perpetuate geographic and racial disparities in cardiovascular outcomes among CKD patients.

Ahmad et al. provide valuable epidemiological insights into cardiovascular mortality trends in CKD patients. However, the stable mortality rates they document, contrasting with improvements in the general population, underscore the urgent need for comprehensive intervention strategies that address therapeutic underutilization, healthcare access barriers, and systematic implementation of evidence-based care. Only through such multifaceted approaches can we hope to improve cardiovascular outcomes for the millions of Americans living with CKD.

Dr. Shaher Yar conceived, wrote, and revised the manuscript. Dr. Zahin Shahriar validated, edited, & compiled the manuscript. Dr. Sumaiya Ahmed reviewed the manuscript. Dr. Muhammad Shehzad Asif supervised the research.

The authors declare no conflicts of interest.