Excessive HDL-C ranges and cardiovascular dangers

In a latest research printed within the American Journal of Cardiology, researchers carried out a potential cohort research within the normal inhabitants enrolled in the UK (UK) Biobank to know the gender-based genetic foundation of cardiovascular illnesses (CVDs) arising as a result of very excessive ranges of high-density lipoprotein ldl cholesterol (HDL-C), i.e., >100 mg/100 ml.

Research: Very Excessive Excessive-Density Lipoprotein Ldl cholesterol Ranges and Cardiovascular Mortality. Picture Credit score: nobeastsofierce / Shutterstock


In medical observe, HDL-C is taken into account good ldl cholesterol; nevertheless, some latest research have instructed that gene alleles related to greater HDL-C ranges are disproportionately related to safety from CVDs. Girls have greater HDL-C ranges than males, elevating the necessity for exploring various CVD threat patterns by gender. Notably, girls inherently have physiologic modulators of lipid metabolism.

In regards to the research

In accordance with the authors, the current research is without doubt one of the first to research the genomic foundation for the elevated HDL-C ranges stratified by gender.

The research inhabitants comprised UK Biobank enrollees aged between 37 and 73 years who didn’t have coronary artery illness (CAD), assessed by way of pre-specified standards. The UK Biobank recruited these members between 2006 and 2010; furthermore, they used a regular questionnaire to collect their sociodemographic knowledge, well being standing, pre-diagnosed illnesses, household historical past, and way of life habits, together with alcohol consumption frequency and smoking historical past, and subsequently, linking this knowledge to Hospital Episode Statistics (HES) knowledge.

Additional, UK Biobank maintained a file of every participant’s weight, physique mass index (BMI), top, and blood strain (BP). The common follow-up lasted for 9 years; nevertheless, follow-up additionally led to case of cardiovascular loss of life, all-cause loss of life, or lack of follow-up.

The researchers explored six classes of HDL-C ranges, lower than 30 mg/100 ml, greater than 30 mg/100 ml however lower than 40 mg/100 ml, better than 40 however lower than equal to 60 mg/100 ml (reference class),  better than 60 mg/100 ml however lower than equal to 80 mg/100 ml, >80 mg/100 ml, and >100 mg/100 ml.

As well as, they used Cox proportional hazards fashions to compute hazard ratios (HR) and 95% confidence intervals (CI) for all-cause mortality throughout all 5 HDL-C classes contemplating the sixth class as a reference.

The group carried out the Evaluation of Variance for usually distributed and the Kruskal-Wallis take a look at for non-normally distributed steady variables, and the chi-square take a look at for categoric variables reported as imply § customary deviation (SD) and frequency, respectively. Moreover, they used interplay analyses to determine the gender-based variations (males/girls. total) between excessive HDL-C and cardiovascular outcomes.

Lastly, the group created a weighted genetic threat rating (GRS) based mostly on the 142 single nucleotide polymorphisms (SNPs) related to HDL-C in a large-scale genome-wide affiliation research. The variants included within the GRS ranged from common-to-rare (minor allele frequency <5%) variants with small to modest and huge impact sizes, respectively. The group introduced coefficients of the affiliation between these SNPs and HDL-C to supply the genetic foundation of the findings of this research.


Two % of the entire male inhabitants within the UK Biobank had >80 mg per 100 ml HDL-C concentrations (very excessive), and, consequently, they had been almost at two-fold greater adjusted threat of cardiovascular and all-cause mortality in comparison with these with regular HDL-C ranges of greater than 40 and fewer than equal to 60 mg per 100 ml (regular). Likewise, girls with very excessive HDL-C ranges constituting 11% of all girls enrolled within the UK Biobank, had no mortality profit in comparison with these with regular HDL-C ranges after accounting for confounders.

Thus, excessive (>60mg/100 ml) HDL-C ranges are nonprotective in women and men and never deemed a dependable marker of atheroprotection per present medical practices. Nevertheless, very excessive (>80 mg/100 ml) HDL-C ranges are markers of excessive threat in males alone. These findings partially elucidate the shortage of usefulness of all pharmaceutical interventions focused at rising HDL-C ranges.

Primarily based on affected person profiles, the authors famous that sufferers encompassed throughout the excessive HDL-C class had been extra typically girls with decrease BMI and triglyceride ranges who had been nondiabetic and didn’t endure from hypertension. Although alcohol consumption raises HDL-C ranges, this research covariate didn’t weaken the impact of excessive HDL-C ranges. Equally, genetic covariates, similar to HDL-associated SNPs, didn’t alter the research findings. Nevertheless, conflicting with prior findings, the HDL-C GRS integrating uncommon and customary genetic variants didn’t weaken the outcomes linked to excessive HDL-C ranges.

Moreover, the authors famous that the sufferers with excessive HDL-C ranges had a compromised HDL-C particle, which altered its construction and performance. Intriguingly, HDL-C particle, as a result of its pro- and anti inflammatory properties, influenced the immune system; thus, its excessive ranges could be manifesting as greater systemic irritation. Nevertheless, the authors famous that C-reactive protein ranges had been a lot diminished in sufferers falling beneath the very best HDL-C inhabitants subset, possible as a result of a a lot lesser frequency of proinflammatory CVD threat components.


To conclude, interventions focused at decreasing the danger related to very excessive HDL-C ranges in males warrant additional research as a result of they appeared to pose a nonlinear threat. Importantly, it ought to be an necessary consideration when utilizing HDL-C measurements in routine to estimate CVD threat within the normal inhabitants.

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