Familial hypercholesterolaemia is the most commonly encountered genetic condition that predisposes individuals to premature cardiovascular disease. Nevertheless, most patients are undiagnosed, and treatment is often suboptimal even when the diagnosis seems certain. Advances in molecular technologies are reshaping our understanding of this condition, including revision upwards of the population prevalence. Furthermore, the underlying pathophysiological complexity has been exposed by the range of causative genetic loci, breadth of types and classes of rare disease-causing variants, and polygenic basis of the phenotype in many patients. Genetic testing is not always helpful or definitive. Familial hypercholesterolaemia can be envisioned as a group of related disorders, of which the classic 'textbook' phenotype is a subset. Features such as clinical stigmata, family history of dyslipidaemia or cardiovascular disease, and presence of a rare pathogenic variant all increase diagnostic certainty. However, even in the absence of these elements, the essential feature remains an elevated level of plasma LDL cholesterol, which alone should prompt a dialogue between the care provider and the patient on lifestyle modification and lipid-lowering therapy as the foundation of a long-term strategy to prevent or delay the onset of cardiovascular disease.

Thus, LPL FCS and non-LPL FCS are largely phenotypically similar. However, LPL FCS patients have lower postheparin LPL activity and a trend toward higher TGs, whereas low-density lipoprotein cholesterol was higher in non-LPL-FCS patients.

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. While 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, while 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.

Background Severe hypertriglyceridemia (serum triglyceride >10 mmol L−1) is implicated in ~9% of acute pancreatitis cases. Certain guidelines list severe hypertriglyceridemia as an indication for plasmapheresis. Objective We assembled the natural trajectory of triglyceride levels in patients with acute pancreatitis due to severe hypertriglyceridemia who were managed conservatively without plasmapheresis to evaluate the effectiveness of this approach. Methods A retrospective chart review was performed on 22 hospital admissions for acute pancreatitis episodes considered to be caused by severe hypertriglyceridemia. Patients were managed supportively, with cessation of oral intake (NPO) and intravenous hydration. Insulin infusion was used in 12 patients to manage concurrent hyperglycaemia. Results Triglyceride levels for the group were evaluated using a mixed‐effects model. The average triglyceride level fell from 45.4 mmol L−1 on presentation to 13.3 mmol L−1 within 48 h, corresponding to a mean 69.8% decrease. Regression analysis showed a triglyceride half‐life of 30.6 h. Findings were similar for NPO‐only and insulin infusion subgroups. Conclusion Patients with severe hypertriglyceridemia and acute pancreatitis can be conservatively managed safely and effectively without plasmapheresis.

Dyslipidaemias encompass about two dozen relatively rare monogenic disorders and syndromes for which the genetic basis has largely been defined. In addition, the complex polygenic basis of disturbed lipids and lipoproteins has been characterised in many patients, and has been shown to result from accumulation of many common polymorphisms with small effects on lipids. Genetic technologies, including dedicated genotyping and sequencing methods can detect both rare and common DNA variants underlying dyslipidaemias. Some dyslipidaemias may be clinically silent for years, but early diagnosis, including genetic diagnosis, may permit early intervention to prevent or delay deleterious downstream clinical consequences, such as premature vascular disease or acute pancreatitis. The potential clinical utility of genetic testing for familial hypercholesterolaemia, familial chylomicronaemia syndrome, lysosomal acid lipase deficiency and some others will increase demand for reliable genetic diagnostic methods. We review some current technologies, such as targeted next-generation sequencing that seem to be helpful with DNA diagnosis of dyslipidaemias. We also address technical, biological and clinical limitations of genetic testing in dyslipidaemias. Finally, genetic counselling issues, the potential impact of results on patients and health care providers, current gaps and future directions will be discussed.