Moderately lower LDL-C and systolic blood pressure (SBP) have independent, multiplicative and cumulative effects on the risk of cardiovascular events, according to results from a new study presented Aug. 29 during ESC Congress 2016 in Rome.

Using a 2x2 factorial Mendelian randomization study design, researchers looked at data from 102,000 persons (mean age of 60.2 percent, 57 percent women) enrolled in one of 14 prospective cohort or case-control studies as part of the U.S. National Heart, Lung, and Blood Institute database of genotypes and phenotypes program. Participants were randomly allocated based on genetic LDL-C and SBP scores to one of four groups: a reference group; a group with lower SBP; a group with lower LDL-C and a group with both lower LDL-C and lower SBP.

Results showed a total of 14,369 major vascular events during up to 32 years of follow-up. Participants with a lower LDL-C score had 12.1 mg/dl (0.31 mmol/L) lower LDL-C and a corresponding 22 percent lower risk of major vascular events (MVE). When adjusted for a standard decrement, each mmol/L lower LDL-C was associated with a 54 percent lower risk of MVE. Similarly, participants with a lower SBP genetic score had 3.0 mmHg lower SBP and a corresponding 17 percent lower risk of MVE. When adjusted for a standard decrement, each 10 mmHg lower SBP was associated with a 44 percent lower risk of MVE.

According to lead investigator Brian A. Ference, MD, MPhil, MSc, FACC, from Wayne State University School of Medicine, Detroit, MI, the effects were “substantially and significantly larger” than previous reductions of approximately 20 percent seen in both previous statin and BP lower trials, thus confirming that LDL-C and SBP have both causal and cumulative effects on cardiovascular events.

Meanwhile, participants in the group with both lower LDL-C and lower SBP genetic scores had 12.2 mg/dl lower (0.31 mmol/L) LDL-C and 3.1 mmHg lower SBP and a corresponding 45.8 percent lower risk of MVE. Ference notes that combined exposure to both lower LDL-C and lower SBP was associated with a significantly greater reduction in the risk of MVE as compared to lower LDL alone (p=1.4x10-14) and as compared to lower SBP alone (p=1.8x10-23). In addition, the effect of combined exposure to lower LDL-C and SBP was slightly greater than the expected effect derived from multiplying the effect of lower LDL-C on the risk of MVE by the effect of lower SBP.

“Because the effects are multiplicative and cumulative over time, long-term exposure to the combination of modestly lower LDL-C and SBP has the potential to dramatically lower the lifetime risk of cardiovascular disease, even among persons with apparently normal cholesterol and blood pressure levels,” Ference said. “Our study confirms that cardiovascular events are largely preventable and suggests that prevention of cardiovascular disease can be substantially improved and simplified by designing prevention programs that promote long-term exposure to the combination of lower LDL-C and lower SBP beginning in early adulthood.”

Keywords: ESC Congress, Blood Pressure, Genotype, National Heart, Lung, and Blood Institute (U.S.), Phenotype, Random Allocation, Blood Pressure Determination, Cardiovascular Diseases, Cholesterol

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