From Lipids to Inflammation: New Approaches to Reducing Atherosclerotic Risk

    Research output: Contribution to journalArticle

    81 Citations (Scopus)

    Abstract

    The introduction of statins ≈30 years ago ushered in the era of lipid lowering as the most effective way to reduce risk of atherosclerotic cardiovascular disease. Nonetheless, residual risk remains high, and statin intolerance is frequently encountered in clinical practice. After a long dry period, the field of therapeutics targeted to lipids and atherosclerosis has entered a renaissance. Moreover, the demonstration of clinical benefits from the addition of ezetimibe to statin therapy in subjects with acute coronary syndromes has renewed the enthusiasm for the cholesterol hypothesis and the hope that additional agents that lower low-density lipoprotein will decrease risk of atherosclerotic cardiovascular disease. Drugs in the orphan disease category are now available for patients with the most extreme hypercholesterolemia. Furthermore, discovery and rapid translation of a novel biological pathway has given rise to a new class of cholesterol-lowering drugs, the proprotein convertase subtilisin kexin-9 inhibitors. Trials of niacin added to statin have failed to demonstrate cardiac benefits, and 3 cholesterol ester transfer protein inhibitors have also failed to reduce atherosclerotic cardiovascular disease risk, despite producing substantial increases in HDL levels. Although the utility of triglyceride-lowering therapies remains uncertain, 2 large clinical trials are testing the influence of omega-3 polyunsaturated fatty acids on atherosclerotic events in hypertriglyceridemia. Novel antisense therapies targeting apolipoprotein C-III (for triglyceride reduction) and apo(a) (for lipoprotein(a) reduction) are showing a promising trajectory. Finally, 2 large clinical trials are formally putting the inflammatory hypothesis of atherosclerosis to the test and may open a new avenue for cardiovascular disease risk reduction.

    Original languageEnglish (US)
    Pages (from-to)732-749
    Number of pages18
    JournalCirculation Research
    Volume118
    Issue number4
    DOIs
    StatePublished - Feb 19 2016

    Fingerprint

    Hydroxymethylglutaryl-CoA Reductase Inhibitors
    Cardiovascular Diseases
    Inflammation
    Lipids
    Atherosclerosis
    Hope
    Triglycerides
    Cholesterol
    Clinical Trials
    Apolipoprotein C-III
    Proprotein Convertases
    Cholesterol Ester Transfer Proteins
    Subtilisin
    Lipoprotein(a)
    Hypertriglyceridemia
    Niacin
    Omega-3 Fatty Acids
    Risk Reduction Behavior
    Therapeutics
    Acute Coronary Syndrome

    Keywords

    • cardiovascular diseases
    • cholesterol
    • high density lipoprotein cholesterol
    • low density lipoprotein cholesterol
    • triglycerides

    ASJC Scopus subject areas

    • Physiology
    • Cardiology and Cardiovascular Medicine

    Cite this

    From Lipids to Inflammation : New Approaches to Reducing Atherosclerotic Risk. / Shapiro, Michael; Fazio, Sergio.

    In: Circulation Research, Vol. 118, No. 4, 19.02.2016, p. 732-749.

    Research output: Contribution to journalArticle

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