Both the risk and benefit of changes in LDL and systolic blood pressure (SBP) on atherosclerotic cardiovascular disease (ASCVD) are proportional to cumulative exposure, according to findings from a new study presented at ESC Congress 2020. Researchers also noted the benefits of a Lifetime Risk equation based on cumulative exposure to LDL and SBP that accurately predicts lifetime risk of CVD, estimates benefits of lowering LDL and SBP, and identifies the age and intensity at which each person should begin to lower LDL and SBP to achieve their preferred target goal.

Researchers led by Brian A. Ference, MD, FACC, of the University Of Cambridge, UK, conducted a Mendelian randomization (MR) study among 184,305 (60,601 cases) participants enrolled in the CARDIoGRAMplusC4D consortium to estimate the effect of each mmolyear of exposure to LDL, and each mmHg-year of exposure to SBP on the risk of major coronary events (MCE). MR was then used to measure the effect of naturally random allocation to 1 mmol/L change in LDL or 10 mmHg change in SBP on the risk of MCE during each year of life (between ages 45-75 years) among 445,675 (23,032 cases) participants enrolled in the UK Biobank.

In addition to measuring the effect of exposure, researchers also compared the effect of each mmol-year of LDL and each mmHg-year of SBP on the risk of MCE estimated in the CARDIoGRAMplusC4D Consortium with UK Biobank findings to assess whether the effect of LDL and SBP on the risk of MCE increases over time. These findings were then used to construct and compare a Lifetime Risk equation based on cumulative exposure to LDL and SBP .

Overall results found each mmol-year of LDL was associated with a 1.87% proportional change in risk of MCE; and each mmHg-year of SBP was associated with a 0.17% proportional change in risk (95%CI: 0.16-0.19, p=5.10E-76) among CARDIoGRAMplusC4D patients. According to Ference, these estimates were nearly identical to those observed among patients in UK Biobank. Additionally, the new Lifetime Risk equation more accurately predicted lifetime risk of MCE than the Framingham Lifetime Risk equation; more accurately predicted 10-year risk than the Pooled Cohort Equation; and accurately predicted the benefit of lowering LDL and SBP compared with other randomized trials.

"The results of this study confirm the cumulative exposure hypothesis by showing that the effect of LDL and SBP on the risk of ASCVD, and the benefit of lowering LDL and SBP, increases with each increasing year of exposure," Ference said. "This study also shows that the cumulative effect of LDL and SBP can be quantified in terms of mmol-years of exposure to LDL and mmHg-years of exposure to SBP."

Clinical Topics: Dyslipidemia, Prevention, Lipid Metabolism

Keywords: ESC Congress, ESC20, Lipoproteins, Primary Prevention

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