What does this research mean for the field?

Extremely high HDL-C levels are associated with increased cardiovascular mortality, indicating a U-shaped relationship with risk. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.CHALLENGES_CONSENSUS.

What question did this study set out to answer?

This research examines the impact of extremely high HDL-C levels on cardiovascular mortality.

February 2, 2026European journal of medical research0 citationsOpen Access

Association between very high HDL-C levels and cardiovascular mortality

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Dyslipidemia (n=3758). Intervention: Very high HDL-C levels (≥ 90 mg/dL in men or ≥ 110 mg/dL in women) vs. Normal HDL-C levels (50–69 mg/dL). Primary outcome: Cardiovascular mortality (HR 1.52, 95% CI 1.04-2.24, p=0.03).

SSSahrish Jaleel Shaikh FAFarman Ali SSSadam Hussain Shaikh

Resultado clave

Very high HDL-C levels were independently associated with increased cardiovascular mortality compared to normal HDL-C levels (adjusted HR 1.52), demonstrating a U-shaped relationship.

Puntos clave

This research examines the impact of extremely high HDL-C levels on cardiovascular mortality.
Analyzed data on HDL-C levels and cardiovascular mortality rates.
Investigated relationships using statistical models to determine independent associations.
Studied a range of HDL-C values to assess the consistency of outcomes.
Found that very high HDL-C levels are linked to increased cardiovascular mortality.
Indicated a potential U-shaped relationship where both low and high levels may be risky.
Emphasized the need for careful evaluation of high HDL-C values in clinical settings.

Diseño del estudio

Tipo

Cohort (n=3,758)

Multicéntrico

PICO estructurado

Does very high HDL-C increase cardiovascular mortality in adults without prior major cardiovascular events?

Población

3,758 adults aged 18 and older without prior major cardiovascular events who underwent lipid profiling, followed for a median of 5.9 years.

Exposición

Very high HDL-C levels (≥90 mg/dL in men or ≥110 mg/dL in women)

Comparador

Normal HDL-C levels (50–69 mg/dL)

Resultado

Cardiovascular mortality (death attributable to myocardial infarction, stroke, sudden cardiac death, or heart failure) over a median follow-up of 5.9 yearshard clinical

Extremely high HDL-C levels are paradoxically associated with increased cardiovascular mortality, challenging the traditional view of HDL-C as uniformly cardioprotective.

Resultado numérico

Hazard Ratio: 1.52 (95% CI 1.04–2.24)

Tasa de eventos absoluta: 11.3% vs 4.8%

valor p: p=0.03

Limitaciones

Retrospective, single-center design precluding causal inference
May limit generalizability
Absence of direct assessments of HDL functionality and particle characteristics
Potential for residual confounding

Resumen

Extremely high HDL-C levels were independently associated with increased cardiovascular mortality, suggesting a U-shaped relationship. These findings warrant cautious interpretation of high HDL-C values in clinical practice.

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Cite This Study

Shaikh et al. (Sat,) conducted a cohort in Dyslipidemia (n=3,758). Very high HDL-C levels (≥ 90 mg/dL in men or ≥ 110 mg/dL in women) vs. Normal HDL-C levels (50–69 mg/dL) was evaluated on Cardiovascular mortality (HR 1.52, 95% CI 1.04-2.24, p=0.03). Very high HDL-C levels were independently associated with increased cardiovascular mortality compared to normal HDL-C levels (adjusted HR 1.52), demonstrating a U-shaped relationship.

synapsesocial.com/papers/6980fe00c1c9540dea80fbd5 https://doi.org/https://doi.org/10.1186/s40001-026-03973-1