• LDL, BP Combine Forces Like 'Pack-Years' for the Arteries

    Study findings likely to lead to combined risk calculator for guidelines

    PARIS -- Blood pressure and cholesterol have independent effects that add up in a dose-dependent manner akin to the concept of cigarette "pack-years," a mendelian randomization study found.

    Lifelong lower blood pressure due to genetic variation -- a median 2.9 mm Hg systolic difference for those with a better than average profile on 61 genetic exome variants linked to blood pressure -- was associated with an 18% lower risk of major coronary events (P<0.001).

    Those with a better than average profile of 100 LDL-lowering genetic alleles -- a median of 14.7 mg/dL lower -- had a 27% lower risk of major coronary events (P<0.001), as Brian Ference, MD, MPhil, of the Centre for Naturally Randomized Trials at the University of Cambridge, England, reported here at the European Society of Cardiology meeting and online in JAMA.

    But those with favorable genetic profiles for both, resulting in a median 13.9-mg/dL lower LDL and 3.1-mm Hg lower systolic pressure, had a 39% lower risk for major coronary events (P<0.001).

    "This is really quite encouraging for quite small differences over a long period of time have a real impact on risk," said session study discussant Jemma Hopewell, PhD, of the Nuffield Department of Population Health at the University of Oxford, England. But she added, "we must remember these estimates may not apply to long-term medication use."

    The good news is that the findings are agnostic of method used to achieve them, Ference noted at a press conference for the late-breaking clinical trial session. Whatever diet or method works to lower blood pressure, "that's the best way for that person if they can maintain that over time."

    His factorial analysis of the UK Biobank's 438,952 participants with genetic and biomarker data affirmed the dose-dependent associations between genetic risk scores and LDL and systolic pressure.

    With these "naturally randomized" data, a combination lifetime risk calculator is being developed for inclusion in the ESC guidelines to complement its SCORE risk tables by next year, Ference told MedPage Today at the press conference.

    Sidney Smith, MD, of the University of North Carolina at Chapel Hill and a past president of the American Heart Association, suggested that this approach to risk is going to be seen in guidelines across the board.

    "If you begin to think about risk in lowering LDL rather than a number to start at, that's where the AHA guidelines are, and it appears that is where the European Society of Cardiology is," he said, referring to the newly released ESC lipid guidelines.

    "Say we give you an LDL cholesterol of 90," he told MedPage Today. "Your risk of having an event is not identified solely by 90. If you are a smoker, if you have diabetes, if you have high blood pressure, to name just a few, the presence of those factors just pounding away will render the endothelium much more likely to be damaged by an LDL of 90 than if you don't."

    While it has not yet entered into the guidelines, "we're beginning to think about LDL cholesterol like cigarette smoking. How many pack-years do you have? How many years has your LDL cholesterol been up at a given level?"

    "Should we be thinking about LDL pack-years from now on?" posited session moderator Frank Ruschitzka, MD, of the University of Zurich.

    The concept could be akin to that, recognizing that about half of LDL is inherited and the other half acquired, Ference replied.

    But Hopewell cautioned that it was unclear whether the UK Biobank results really represented lifetime risk, as the cohort had about 10 years of follow-up and most remain alive.

     

    Ference reported financial disclosures for Amgen, Merck, Regeneron, Novartis, Esperion Therapeutics, Ionis Pharmaceuticals, The Medicines Company, Novo Nordisk, Sanofi, Pfizer, Eli Lilly, dalCOR, Silence Therapeutics, Integral Therapeutics, CiVi Pharma, KrKa Pharmaceuticals, Mylan, the American College of Cardiology, the European Atherosclerosis Society, the European Society of Cardiology, and Afimmune.

    Source:

    JAMA

    Source Reference: Ference BA, et al "Association of Genetic Variants Related to Combined Exposure to Lower Low-Density Lipoproteins and Lower Systolic Blood Pressure With Lifetime Risk of Cardiovascular Disease" JAMA 2019; DOI: 10.1001/jama.2019.14120.

    Read the original article on Medpage Today: LDL, BP Combine Forces Like 'Pack-Years' for the Arteries

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