A Modern Approach to Dyslipidemia
Amanda J. Berberich, Robert A. Hegele · 2021 · 474 citationsRead the paper
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.
What the full text shows
Deployed in practice- Nonfasting standard lipid profiles provide an accurate estimate of LDL-C for most patients without hypertriglyceridemia. — <5% error (Patients screened without HTG)
- Hypertriglyceridemia (HTG) is a significant cause of pancreatitis. — 10% to 14% of pancreatitis cases (General pancreatitis population)
- Rhabdomyolysis occurs at a very low frequency during statin treatment. — 1 in 100,000 individuals per year (Patients on statin therapy)
- SAMS with CK elevations >10x ULN occurs rarely during statin treatment. — 1 in 10,000 individuals per year (Patients on statin therapy)
- The Friedewald formula for LDL-C becomes inaccurate at high triglyceride levels. — TG >4.5 mmol/L (>400 mg/dL) (LDL-C calculation from standard lipid profile)
- Triglyceride levels fall rapidly after cessation of oral intake. — half-life of ~30 hours (Patients with HTG-associated pancreatitis)
- Setup
- Review of clinical guidelines, cohort studies (including one with >900 individuals with isolated low HDL-C), and pharmacological trial data.
- How
- The paper provides a clinical review and synthesis of current lipid metabolism knowledge, diagnostic algorithms, and treatment guidelines. It incorporates data from cohort studies, N-of-1 trials, and genetic analysis of lipid phenotypes.
- Limitations
- Lack of definitive evidence supporting plasmapheresis or insulin infusions over conservative management for HTG-associated pancreatitis. · Lack of reliable and accessible clinical assays to measure HDL function. · Directly measured LDL-C methods are expensive and not widely standardized.
Summarized by Gemma 4 from the open-access full text · 2 Oct 2026. Read it