• Study: Lifetime Risk Matters in Lipid Management

    Comprehensive study suggests not waiting for 10-year risk to catch up

    Starting cholesterol-lowering therapy early in life may help reduce cardiovascular disease (CVD) risk decades later, affirmed a large longitudinal study that generated a tool for lifetime risk assessment.

    Thirty-year risk of atherosclerotic CVD (coronary heart disease events or ischemic stroke) grew stepwise with non-HDL cholesterol levels, whereas a 50% lower non-HDL cholesterol level was associated with reduced risk by the age of 75 years.

    Importantly, "this risk reduction was greater the earlier cholesterol concentrations were reduced," reported Stefan Blankenberg, MD, of University Heart & Vascular Center Hamburg in Germany, and collaborators in The Lancet.

    For example, a woman younger than 45 with non-HDL cholesterol of 3.7-4.8 mmol/L and at least two risk factors has an estimated 15.6% chance of a CVD event by age 75 -- but only 3.6% if she manages to halve that cholesterol with a lipid-lowering intervention.

    Future research needs to address whether young people with a high lifetime risk but low 10-year risk would benefit from early rather than late lipid-lowering intervention, Blankenberg's team said.

    Early cholesterol-lowering therapy -- perhaps starting "at much lower 10-year risk thresholds of atherosclerotic [CVD] than are currently recommended for consideration of statin therapy" -- could be beneficial, agreed Jennifer Robinson, MD, MPH, of the University of Iowa in Iowa City, in an accompanying commentary.

    The study's findings led the group to create a visual tool estimating a person's CVD risk by age 75 and corresponding risk reduction if non-HDL cholesterol were to be halved. The tool estimates individual risk of CVD according to age, sex, non-HDL cholesterol level, and number of cardiovascular risk factors.

    Current guidelines and risk calculators are mostly based on 10-year risk, underestimating lifetime risk, according to Blankenberg and colleagues.

    "Considerable uncertainty exists about the extent to which slightly increased or apparently normal cholesterol concentrations affect lifetime cardiovascular risk and about which thresholds should be used to merit a treatment recommendation, particularly in young people," the investigators noted.

    "Additionally, although high-intensity statins have similar safety profiles to moderate-intensity statins or placebo in trials with up to 7 years of follow-up, there are no randomised, controlled, long-term safety data for decades-long treatment. If adverse events occur, they would alter the benefit-to-harm ratio of the net-benefit calculation," according to Robinson.

    Newer therapies that continue to be investigated in this realm include PCSK9 inhibitors and the siRNA drug inclisiran.

    Blankenberg's study was based on Multinational Cardiovascular Risk Consortium data from 19 countries across Europe, Australia, and North America.

    Nearly 400,000 people with no CVD at baseline were followed for a median 13.5 years and up to 43.6 years. This group, with 48.7% women, had a median age of 51 years.

    The overall cohort was roughly split between derivation and validation cohorts for the creation of the CVD risk estimation tool.

    A person's 30-year risk of atherosclerotic CVD (coronary heart disease events or ischemic stroke) grew stepwise with non-HDL cholesterol levels beyond 2.6 mmol/L:

    • Women with non-HDL cholesterol 2.6-3.7 mmol/L: adjusted HR 1.1 (95% CI 1.0-1.3)
    • Women with non-HDL cholesterol 5.7 mmol/L or greater: adjusted HR 1.9 (95% CI 1.6-2.2)
    • Men with non-HDL cholesterol 2.6-3.7 mmol/L: adjusted HR 1.1 (95% CI 1.0-1.3)
    • Men with non-HDL cholesterol 5.7 mmol/L or greater: adjusted HR 2.3 (95% CI 2.0-2.5)


    Absolute risk reductions were bigger with two or more CVD risk factors and in men. "Within each category, the greatest effect was found for the youngest individuals," the researchers noted.

    Patient outcome ascertainment could have been better in this kind of large longitudinal study, the study authors acknowledged. Another limitation was that only baseline blood lipid data were available for analysis, leaving out information about cholesterol changes during follow-up or about the initiation of lipid-lowering therapy.

    What's more, study participants were largely people with European ancestry, Blankenberg's group said.

    "For populations of non-European ancestry and those in low-income and middle-income countries, more prospective cohort data are needed," Robinson urged.

    Blankenberg reported grants and personal fees from Abbott Laboratories, Bayer, Siemens, and Thermo Fisher Scientific; grants from Singulex; and personal fees from AstraZeneca, Amgen, Medtronic, Pfizer, and Roche.

    Robinson disclosed institutional grants from Acasti, Amarin, Amgen, AstraZeneca, Eisai, Eli Lilly, Esperion, GlaxoSmithKline, The Medicines Company, Merck, Novartis, Novo-Nordisk, Pfizer, Regeneron, Sanofi, and Takeda as well as consulting for Akcea, Amgen, The Medicines Company, Merck, Novartis, Novo-Nordisk, Pfizer, Regeneron, and Sanofi.


    The Lancet

    Source Reference: Brunner FJ, et al "Application of non-HDL cholesterol for population-based cardiovascular risk stratification: results from the Multinational Cardiovascular Risk Consortium" The Lancet 2019; DOI: 10.1016/S0140-6736(19)32519-X.

    The Lancet

    Source Reference: Robinson JG "The next treatment paradigm in cardiovascular prevention?" The Lancet 2019; DOI: 10.1016/S0140-6736(19)32949-6.


    Read the original article on Medpage Today: Study: Lifetime Risk Matters in Lipid Management

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