![]() ![]() ![]() Previous studies including older individuals suggest that the causal relation between LDL-C and (cardiovascular) disease is absent at old age. In longitudinal analysis, high GRS was associated with increased all-cause mortality in individuals > 90 years, with a 13% increased risk in individuals with the highest LDL GRS ( P-trend = 0.043).Ĭonclusion: Results of the current study indicate that a genetic predisposition to high LDL-C levels contributes to mortality throughout life, including in the oldest old, and a beneficial LDL genetic risk profile is associated with familial longevity. Moreover, individuals with a genetic predisposition for longevity had significantly lower LDL GRS compared with age-matched individuals of the general population. The frequency of LDL-increasing alleles decreased with increasing age. Results: Up to 90 years of age, in each age stratum individuals with high LDL GRS had higher LDL-C levels ( P = 0.010 to P = 1.1 x 10 −16). We assessed the association between the LDL GRS and LDL-C levels, chronological age, familial longevity and mortality. The LDL GRS was calculated in three Dutch cohorts: the Leiden Longevity Study (LLS) ( n = 3270), the Leiden 85-plus study ( n = 316) and the Rotterdam Study ( n = 4035). Methods: A weighted GRS was created using 51 single nucleotide polymorphisms associated with LDL-C levels. In the current study, we used an LDL genetic risk score (GRS) to overcome this problem. However, in old age plasma low-density lipoprotein cholesterol (LDL-C) may not reflect the lifetime level due to reverse causality, and hence the risk may be underestimated. Background: Observational studies in older subjects have shown no or inverse associations between cholesterol levels and mortality. ![]()
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