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Is High Serum LDL/HDL Cholesterol Ratio an Emerging Risk Factor for Sudden Cardiac Death? Findings from the KIHD
Setor K Kunutsor1, Francesco Zaccardi2, Jouni Karppi3
1School of Clinical Sciences, University of Bristol, Learning & Research Building (Level 1), Southmead Hospital.
Insights
A high ratio of low-density lipoprotein cholesterol (LDL-c) to high-density lipoprotein cholesterol (HDL-c) significantly increases sudden cardiac death (SCD) risk in middle-aged men. Individual LDL-c or HDL-c levels did not show a significant association with SCD risk.
Area of Science:
- Cardiovascular Medicine
- Lipid Metabolism
- Epidemiology
Background:
- Low-density lipoprotein cholesterol (LDL-c) and high-density lipoprotein cholesterol (HDL-c) are key lipid components influencing cardiovascular health.
- Previous studies have suggested links between LDL-c and HDL-c individually with sudden cardiac death (SCD) risk.
- The association between the LDL-c/HDL-c ratio and SCD risk remains under-investigated.
Purpose of the Study:
- To investigate the relationship between serum LDL-c, HDL-c, and the LDL-c/HDL-c ratio with the risk of SCD.
- To determine if the LDL-c/HDL-c ratio is an independent predictor of SCD in middle-aged men.
Main Methods:
- Prospective cohort study involving 2,616 men aged 42-61 years.
- Baseline serum lipoprotein concentrations were measured.
- Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to assess risk over a median follow-up of 23.0 years.
Main Results:
- No significant association was found between individual LDL-c or HDL-c levels and SCD risk.
- A high LDL-c/HDL-c ratio (top quintile) was independently associated with a nearly two-fold increase in SCD risk (HR 1.94, 95% CI 1.21-3.11).
- This association remained significant after adjusting for multiple cardiovascular risk factors.
Conclusions:
- Serum LDL-c and HDL-c levels alone are not significantly associated with SCD risk in this cohort.
- A high LDL-c/HDL-c ratio is an independent risk factor for SCD in middle-aged men.
- Further research is needed to elucidate the underlying mechanisms connecting a high LDL-c/HDL-c ratio to SCD.
Aim:
Low-density lipoprotein cholesterol (LDL-c) and high-density lipoprotein cholesterol (HDL-c), which are components of total cholesterol, have each been suggested to be linked to the risk of sudden cardiac death (SCD). However, the relationship between LDL-c/HDL-c ratio and the risk of SCD has not been previously investigated. We aimed to assess the associations of LDL-c, HDL-c, and the ratio of LDL-c/HDL-c with the risk of SCD.
Methods:
Serum lipoprotein concentrations were assessed at baseline in the Finnish Kuopio Ischemic Heart Disease prospective cohort study of 2,616 men aged 42-61 years at recruitment. Hazard ratios (HRs) (95% confidence intervals [CI]) were assessed.
Results:
During a median follow-up of 23.0 years, a total of 228 SCDs occurred. There was no significant evidence of an association of LDL-c or HDL-c with the risk of SCD. In analyses adjusted for age, examination year, body mass index, systolic blood pressure, smoking, alcohol consumption, physical activity, years of education, diabetes, previous myocardial infarction, family history of coronary heart disease, and serum high sensitivity C-reactive protein, there was approximately a two-fold increase in the risk of SCD (HR 1.94, 95% CI 1.21-3.11; p=0.006), comparing the top (＞4.22) versus bottom (≤2.30) quintile of serum LDL-c/HDL-c ratio.
Conclusion:
In this middle-aged male population, LDL-c or HDL-c was not associated with the risk of SCD. However, a high serum LDL-c/HDL-c ratio was found to be independently associated with an increased risk of SCD. Further research is warranted to understand the mechanistic pathways underlying this association.