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<p>Cardiovascular disease (CVD) remains the leading cause of mortality worldwide, accounting for an estimated 20.5&#xa0;million deaths in 2021, with projections surpassing 23.6&#xa0;million by 2030. Since the mid-20th century, an inverse association between high-density lipoprotein (HDL) levels and CVD risk has been well established, highlighting HDL’s multifaceted cardioprotective roles. HDL facilitates reverse cholesterol transport, attenuates low-density lipoprotein (LDL) oxidation, modulates vascular inflammation, and promotes endothelial repair—each vital to cardiovascular homeostasis. Although LDL-lowering agents such as statins significantly reduce CVD risk, a substantial residual burden remains, underscoring the need for complementary therapeutic strategies. Notably, each 1&#xa0;mg/dL increase in serum HDL correlates with a 2% reduction in CVD risk in men and 3% in women. This review critically examines the molecular mechanisms underlying HDL-mediated cardioprotection and provides an in-depth analysis of HDL-based therapeutic strategies, including apolipoprotein mimetics, reconstituted HDL infusions, and pharmacological modulators. Enhancing HDL functionality, rather than merely increasing HDL levels, may offer promising avenues for addressing the unmet clinical need and reducing the global CVD burden.</p>

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HDL and Cardiovascular Disease: Mechanisms, Therapeutic Advances, and Challenges

  • 期刊论文

  • 发表日期：

    2026年3月3日

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  • Koushik Sen,
  • Abhinaba Sinha

摘要

Cardiovascular disease (CVD) remains the leading cause of mortality worldwide, accounting for an estimated 20.5 million deaths in 2021, with projections surpassing 23.6 million by 2030. Since the mid-20th century, an inverse association between high-density lipoprotein (HDL) levels and CVD risk has been well established, highlighting HDL’s multifaceted cardioprotective roles. HDL facilitates reverse cholesterol transport, attenuates low-density lipoprotein (LDL) oxidation, modulates vascular inflammation, and promotes endothelial repair—each vital to cardiovascular homeostasis. Although LDL-lowering agents such as statins significantly reduce CVD risk, a substantial residual burden remains, underscoring the need for complementary therapeutic strategies. Notably, each 1 mg/dL increase in serum HDL correlates with a 2% reduction in CVD risk in men and 3% in women. This review critically examines the molecular mechanisms underlying HDL-mediated cardioprotection and provides an in-depth analysis of HDL-based therapeutic strategies, including apolipoprotein mimetics, reconstituted HDL infusions, and pharmacological modulators. Enhancing HDL functionality, rather than merely increasing HDL levels, may offer promising avenues for addressing the unmet clinical need and reducing the global CVD burden.