Lifelong genetic exposure to lower levels of both LDL cholesterol (LDL-C) and systolic blood pressure (SBP) is associated with a dose-dependent decreased risk of major coronary events. This finding comes from a new study published in JAMA and presented at the ESC Congress 2019.

The study included data from 438,952 participants enrolled in the UK Biobank. Participants were randomly divided into groups according to genetic LDL-C and SBP scores. The LDL-C score consisted of 100 exome variants previously associated with LDL-C level at the genome-wide level of significance and, similarly, the SBP score consisted of 61 exome variants previously associated with SBP level.

Individuals with an LDL-C genetic score higher than the median had 14.7 mg/dl lower LDL-C levels and a lower risk of major coronary events (OR 0.73, 95% CI 0.70–0.75, P < 0.001) than individuals with an LDL-C genetic score equal to or lower than the median. Similarly, individuals with an SBP genetic score higher than the median had 2.9 mmHg lower SBP levels and a lower risk of major coronary events (OR 0.82, 95% CI 0.79–0.85, P < 0.001) than individuals with an SBP genetic score equal to or lower than the median. Of note, individuals with both genetic risk scores higher than the median had 13.9 mg/dl lower LDL-C levels and 3.1 mmHg lower SBP levels and a log-additive reduction in the risk of major coronary events (OR 0.61, 95% CI 0.59–0.64, P < 0.001).

The investigators emphasize that the relationship between long-term exposure to lower LDL-C and SBP levels and the risk of cardiovascular events is independent, additive and dose-dependent, so that even small reductions in LDL-C and/or SBP levels can have clinically meaningful benefits over the course of a lifetime.