A Modern Approach to Dyslipidemia

Abstract

Lipid disorders involving derangements in serum cholesterol, triglycerides, or both are commonly encountered in clinical practice and often have implications for cardiovascular risk and overall health. Recent advances in knowledge, recommendations, and treatment options have necessitated an updated approach to these disorders. Older classification schemes have outlived their usefulness, yielding to an approach based on the primary lipid disturbance identified on a routine lipid panel as a practical starting point. Although monogenic dyslipidemias exist and are important to identify, most individuals with lipid disorders have polygenic predisposition, often in the context of secondary factors such as obesity and type 2 diabetes. With regard to cardiovascular disease, elevated low-density lipoprotein cholesterol is essentially causal, and clinical practice guidelines worldwide have recommended treatment thresholds and targets for this variable. Furthermore, recent studies have established elevated triglycerides as a cardiovascular risk factor, whereas depressed high-density lipoprotein cholesterol now appears less contributory than was previously believed. An updated approach to diagnosis and risk assessment may include measurement of secondary lipid variables such as apolipoprotein B and lipoprotein(a), together with selective use of genetic testing to diagnose rare monogenic dyslipidemias such as familial hypercholesterolemia or familial chylomicronemia syndrome. The ongoing development of new agents-especially antisense RNA and monoclonal antibodies-targeting dyslipidemias will provide additional management options, which in turn motivates discussion on how best to incorporate them into current treatment algorithms.

Keywords: atherosclerosis; cholesterol; combined hyperlipidemia; dyslipidemia; lipoprotein(a); triglycerides.

Graphical Abstract

Figure 1.

Schematic of plasma lipoprotein metabolism. See text for detailed explanation and abbreviations. Yellow, TG; red, cholesterol ester; orange, free cholesterol; black boxes, apolipoproteins; stippled boxes, receptors or transporters; dashed box borders, accessory proteins.

Figure 2.

Physical manifestations of selected dyslipidemias. In untreated familial hypercholesterolemia (FH) findings include (A and B) xanthelasmas; (B) arcus cornealis; (C and D) extensor tendon xanthomas, indicated by arrows. In untreated dysbetalipoproteinemia, findings include (E) palmar crease xanthomas and (F) tuberous xanthomas (here on elbow). In severe hypertriglyceridemia, manifestations can include (G) eruptive xanthomata and (H) lipemia retinalis. (I) Orange tonsils in Tangier disease (from Sampietro T, Puntoni M, Bigazzi F, et al. Tangier disease in severely progressive coronary and peripheral artery disease. Circulation 2009; 119: 2741-2742). (J) Corneal clouding in lecithin cholesterol acyl transferase deficiency. In abetalipoproteinemia, findings include (K) acanthocytes (indicated by arrows) on peripheral blood film and (J) atypical retinitis pigmentosa.

Figure 3.

Approach to the patient with high LDL-C.

Figure 4.

Approach to the patient with high TG.

Figure 5.

Approach to the patient with statin intolerance.