Management of dyslipidemia, especially through strategies that reduce low-density lipoprotein cholesterol (LDL-C) levels, remains the cornerstone of prevention of atherosclerotic cardiovascular disease (ASCVD). Yet both women and older adults remain suboptimally treated with evidence-based care. Available evidence suggests that for those at sufficiently elevated risk, women benefit similarly to men for the reduction of ASCVD events with proven LDL-C–lowering strategies including statin, ezetimibe, and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor therapy. In primary prevention, female-specific factors (such as premature menopause and history of an adverse pregnancy outcome) serve as “risk enhancers” that can be considered when determining lifestyle and prevention recommendations for women. Additionally, there are special considerations for lipid management in women related to time of conception, pregnancy, and breastfeeding. Available evidence also suggests that adults aged 75 years and older at sufficiently elevated risk, particularly for secondary prevention, also benefit from intensive LDL-C–lowering therapy, including statins, ezetimibe, and PCSK9 inhibitors. Older adults require special considerations for lipid management, including the potential for drug–drug interactions and for other health conditions with competing risks for death that may limit the net benefit of lipid-lowering therapy. These decisions regarding net benefit versus risk can be guided through shared decision making involving the patient for an individualized approach to care. This chapter discusses unique aspects of lipids and lipid-lowering treatments among women and older adults.
In humans, sterols are required for a number of physiologic processes, but excessive sterol production or absorption can be detrimental, because it may contribute to the development of atherosclerosis. Nuclear hormone receptors regulate the absorption of dietary sterols by modulating the transcription of several genes involved in cholesterol metabolism. One of these genes encodes a molecule (adenosine triphosphate [ATP]–binding cassette [ABC] transporter) that transports dietary cholesterol from enterocytes to the intestinal lumen, thereby limiting the amount of cholesterol absorbed. By the same mechanism, ABC transporters also provide an efficient barrier against the absorption of plant sterols. Another key process that affects intestinal sterol absorption is the synthesis of cholesteryl esters. Furthermore, a key protein involved in cholesterol transport, named Niemann–Pick C1–like 1 protein (NPC1L1), has been characterized. The pharmacological treatment of elevated blood cholesterol levels has been dramatically modified over the past 25 years by the introduction of statins; however, many patients cannot reach the target for low-density lipoprotein cholesterol (LDL-C) level, suggesting combination therapy with drugs with different mechanisms of action as a better approach. This chapter focuses on the molecular mechanisms involved in cholesterol absorption and describes the different approaches available that directly or indirectly interfere with cholesterol absorption
