Background and Aims:
Plasma low-density-lipoprotein cholesterol (LDL-c), a well-established causal risk factor for cardiovascular disease, increases with age with a remarkably different gender-specific pattern. Despite these important gender differences, dyslipidemic patients are considered and treated as one. As far as we know, we study for the first time the main gender-specific factors associated with extreme LDL-c levels in young individuals in order to ultimately improve their cardiovascular health management.

Methods:
From 45,000 participants of the Lifelines cohort study who filled in extended questionnaires and provided with biological samples (DNA, Plasma), we selected young women and men (25-40 yrs) with either LDL<1st-percentile (n=120); average LDL-c (n=60) or >99th-percentile (n=120) per gender (total n=600). Using self-reported questionnaires, lifestyle scores were calculated. Genetic origins of dyslipidemia were assessed using targeted next-generation-sequencing. Apolipoproteins (including Lp(a) and PCSK9 were measured.

Results
Our main findings include the observations that:
1) 68% of women present a genetic origin of hypocholesterolemia vs. 55% in men, 
2) Lp(a) concentrations correlate with increased LDL-c in men but not in women
3) An unfavorable lifestyle is associated with higher LDL-c levels in specifically women
4) Women present higher PCSK9 plasma levels than Men

Conclusions:
These findings highlight important gender-specific factors that drive LDL-c to extremes in young individuals (Genetics, Lifestyle) as well as associated risk factors (Lp(a)) which could have immediate repercussions on their cardiovascular health management.

07 - GENDER-SPECIFIC DIFFERENCES AT BOTH EXTREME ENDS OF THE LDL CHOLESTEROL DISTRIBUTION CURVE