What is the clinical evidence from this study?

Study design: Cohort. Population: Chronic kidney disease (n=1061). Intervention: Persistently high BMI (≥23 kg/m²) vs. Consistently low BMI (<23 kg/m²). Primary outcome: Extended major adverse cardiovascular events (eMACEs) (RR 0.279, 95% CI 0.143-0.546, p=<0.001).

What does this research mean for the field?

Persistently high body mass index (≥23 kg/m²) significantly reduces the risk of major adverse cardiovascular events compared to consistently low BMI in patients with chronic kidney disease. Novelty: ClaimNovelty.CONTRADICTORY. Consensus alignment: ConsensusAlignment.CHALLENGES_CONSENSUS.

What question did this study set out to answer?

To explore the relationship between BMI changes over time and cardiovascular events among patients with chronic kidney disease.

March 22, 2026Open Access

Long-term dynamic effect of body mass index on adverse cardiovascular outcomes with targeted maximum likelihood estimation method: result from the KNOW-CKD study

Q: What are the key findings of this study?

Persistently high body mass index (≥23 kg/m²) significantly reduced the risk of extended major adverse cardiovascular events (RR 0.279) compared to consistently low BMI in patients with CKD.

Q: What does this research mean for the field?

Persistently high body mass index (≥23 kg/m²) significantly reduces the risk of major adverse cardiovascular events compared to consistently low BMI in patients with chronic kidney disease. Novelty: ClaimNovelty.CONTRADICTORY. Consensus alignment: ConsensusAlignment.CHALLENGES_CONSENSUS.

Q: What question did this study set out to answer?

To explore the relationship between BMI changes over time and cardiovascular events among patients with chronic kidney disease.

Key Result

Persistently high body mass index (≥23 kg/m²) significantly reduced the risk of extended major adverse cardiovascular events (RR 0.279) compared to consistently low BMI in patients with CKD.

Key Points

To explore the relationship between BMI changes over time and cardiovascular events among patients with chronic kidney disease.
Analyzed data from 1061 patients in the KNOW-CKD study.
Categorized BMI as high (≥ 23 kg/m2) or low (< 23 kg/m2).
Assessed BMI at three time points over a 7-year period.
Used targeted maximum likelihood estimation and marginal structural models to account for time-varying covariates.
Patients with persistently high BMI had a reduced risk of cardiovascular events (relative risk 0.279; P < 0.001) compared to those with low BMI.
Transient BMI fluctuations did not yield cardiovascular benefits.
Findings suggest that sustained high BMI may protect against cardiovascular issues in CKD.

Study Design

Type

Cohort (n=1,061)

Multicenter

Yes

Structured PICO

Does sustained high BMI reduce extended major adverse cardiovascular events in patients with chronic kidney disease?

Population

Adults with chronic kidney disease (CKD stages G1-G5 non-dialysis), mean age 53.9 years, 59.8% male.

Intervention

Sustained high BMI (≥ 23 kg/m2) over a 7-year period.

Comparator

Consistently low BMI (< 23 kg/m2) over a 7-year period.

Outcome

Extended major adverse cardiovascular events (eMACEs), a composite of acute myocardial infarction, hospitalization for unstable angina or heart failure, percutaneous coronary interventions, coronary artery bypass grafting, ischemic or hemorrhagic stroke, symptomatic arrhythmias requiring hospitalization, peripheral arterial disease, and other cardiovascular events necessitating hospitalization or intervention.composite

Sustained high BMI over a 7-year period is associated with a significantly reduced risk of major adverse cardiovascular events in patients with chronic kidney disease, supporting the obesity paradox in this population.

Main Result

Effect estimate: RR 0.279 (95% CI 0.143-0.546)

p-value: p=<0.001

Abstract

The relationship between body mass index (BMI) and cardiovascular outcomes in chronic kidney disease (CKD) remains controversial. While the obesity paradox has been observed in this population, the impact of longitudinal BMI patterns over time is not well established. In this study, we investigated the association between BMI trajectories and the risk of cardiovascular events (CVEs) using data from 1061 patients enrolled in the Korean Cohort Study for Outcome in Patients With Chronic Kidney Disease (KNOW-CKD). BMI was categorized as high (≥ 23 kg/m2) or low (< 23 kg/m2), and assessed at three time points over a 7-year period. We applied targeted maximum likelihood estimation (TMLE) and marginal structural models (MSMs) to adjust for time-varying covariates, including estimated glomerular filtration rate, blood pressure, hemoglobin, albumin, and C-reactive protein, as well as baseline demographic and clinical characteristics. Patients with persistently high BMI had a significantly reduced risk of CVEs (relative risk 0.279; 95% CI 0.143–0.546; P < 0.001) compared to those with consistently low BMI. Transient increases or decreases in BMI did not show the same benefit. Our findings suggest that sustained high BMI may be protective against cardiovascular events in patients with CKD, challenging current weight management recommendations and supporting individualized approaches based on long-term risk profiles.

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