Lower levels of low-density lipoprotein cholesterol (LDL-C) combined with a lower systolic blood pressure (SBP) have synergistic effects in reducing the risk of cardiovascular disease (CVD), according to a study presented at the recent European Society of Cardiology (ESC) Congress 2016 held in Rome, Italy.

“We found that LDL-C and SBP have independent, multiplicative, and cumulative effects on the risk of cardiovascular events ... Even among persons with apparently ‘normal’ cholesterol and blood pressure levels,” said study principal investigator Dr Brian Ference from the Division of Cardiovascular Medicine at Wayne State University School of Medicine in Detroit, Michigan, US.

“A simplified prevention strategy that promotes long-term exposure to the combination of both lower LDL-C and lower SBP may be an effective strategy to prevent CVD,” he added.

The study analysed data from 102,773 participants in 14 case-control or prospective cohort studies who were followed-up for major vascular events (MVE) such as coronary heart disease (CHD)-related death, myocardial infarction (MI), stroke, and coronary revascularization for up to 32 years. [ESC 2016, abstract 3163]

Based on genetic polymorphisms associated with lower LDL-C or SBP levels inherited by the individuals, they were assigned with genetic scores for LDL-C and SBP and divided into four groups: lower SBP, lower LDL-C, combined lower LDL-C and SBP, and a reference group.

Individuals with a lower LDL-C score had 12.1 mg/dL (0.3 mmol/L) lower LDL-C and a corresponding 22 percent lower risk of MVE compared with the reference group (p=3.0x10^-40). When adjusted for a standard decrement, each mmol/L lower LDL-C was associated with a 54 percent reduction in MVE risk, which was significantly greater than the 22 percent reduction in a meta-analysis of statin trials (p=8.0x10^-19). [Lancet 2010;376:1670-1681]

Similarly, individuals with a lower SBP genetic score had 3.0 mmHg lower SBP and a corresponding 17 percent lower risk of MVE (p=2.7x10^-24), equivalent to a 44 percent lower risk of MVE for each 10 mmHg decline in SBP levels. This was significantly greater than the 20 percent reduction observed in a recent meta-analysis of blood pressure-lowering trials (p=1.6x10^-9). [Lancet 2016;387:957-967]

Those in the combined lower LDL-C and SBP group had both 12.1 mg/dL and 3.0 mmHg lower SBP and a corresponding 45.8 percent lower risk of MVE, which was significantly greater than the 22 percent reduction with lower LDL alone (p=1.4x10^-14) or the 17 percent reduction with lower SBP alone (p=1.8x10^-23).

“Long-term exposure to combination of modestly lower LDL-C and SBP has the potential to dramatically reduce the lifetime risk of CVD,” said Ference, explaining that just 1 mmol/L lower LDL and 10 mmHg lower SBP was associated with a 86 percent reduction in MVE risk, including 84 percent lower risk of CHD death (p=1.4x10^-26), which was translated to 36 percent lower risk of all-cause mortality (p=6.8x10^-5).     

Subgroup analyses revealed that the cumulative effect was similar in all subgroups, even among those with LDL-C <3.4 mmol/L and SBP <120 mmHg. This indicates that even people with normal cholesterol and SBP levels could benefit from the combination of lower LDL-C and SBP, according to Ference.

As the study assessed the combined effects of exposure to lower LDL-C and SBP, but not the effects of lowering SBP and LDL-C with medications, Ference cautioned that the study did not suggest that everyone should be treated with medications to lower SBP and LDL-C.

“Further research is needed to identify persons who would benefit most from early intervention to lower LDL-C, SBP, or both as strategy to personalize the prevention of CVD,” he said.