Lifestyle intervention followed by bariatric surgery in 34 morbidly obese patients showed favorable effects on TGs, LDL-C, and apoB. HDL cholesterol and apoA1 was increased, apoB/apoA1 ratio as well as SAA/PON1 ratio reduced, but bariatric surgery did not influence CEC.

Lipoprotein apheresis and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are last therapeutic resorts in patients with familial hypercholesterolemia (FH). We explored changes in lipoprotein subclasses and high-density lipoprotein (HDL) function when changing treatment from lipoprotein apheresis to PCSK9 inhibition. We measured the levels of low-density lipoprotein (LDL) and HDL particle subclasses, serum amyloid A1 (SAA1), paraoxonase-1 (PON1) activity and cholesterol efflux capacity (CEC) in three heterozygous FH patients. Concentrations of all LDL particle subclasses were reduced during apheresis (large 68.0 ± 17.5 to 16.3 ± 2.1 mg/dL, (p = 0.03), intermediate 38.3 ± 0.6 to 5.0 ± 3.5 mg/dL (p = 0.004) and small 5.0 ± 2.6 to 0.2 ± 0.1 mg/dL (p = 0.08)). There were non-significant reductions in the LDL subclasses during evolocumab treatment. There were non-significant reductions in subclasses of HDL particles during apheresis, and no changes during evolocumab treatment. CEC was unchanged throughout the study, while the SAA1/PON1 ratio was unchanged during apheresis but decreased during evolocumab treatment. In conclusion, there were significant reductions in large and intermediate size LDL particles during apheresis, and a non-significant reduction in small LDL particles. There were only non-significant reductions in the LDL subclasses during evolocumab treatment.

High-density lipoproteins (HDL) are a heterogenous group of plasma molecules with a large variety in composition. There is a wide specter in lipid content and the number of different proteins that has been associated with HDL is approaching 100. Given this heterogeneity and the fact that the total amount of HDL is inversely related to the risk of coronary heart disease (CHD), there has been increasing interest in the function of specific HDL subgroups and in what way measuring and quantifying these subgroups could be of clinical importance in determining individual CHD risk. If certain subgroups appear to be more protective than others, it may also in the future be possible to pharmacologically increase beneficial and decrease harmful subgroups in order to reduce CHD risk. In this review we give a short historical perspective, summarize some of the recent clinical findings regarding HDL subclassifications and discuss why such classification may or may not be of clinical relevance.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors reduce the risk of cardiovascular events and all-cause mortality in patients at high risk of cardiovascular disease (CVD). Due to high costs and unknown long-term adverse effects, critical evaluation of patients considered for PCSK9 inhibitors is important. It has been proposed that measuring low-density lipoprotein (LDL) subfractions, or LDL particle numbers (LDL-P), could be of value in CVD risk assessment and may identify patients at high risk of CVD. This review evaluates the evidence for the use of LDL subfractions, or LDL-P, when assessing CVD risk in patients for whom PCSK9 inhibitors are considered as a lipid-lowering therapy. Numerous methods for measuring LDL subfractions and LDL-P are available, but several factors limit their availability. A lack of standardization makes comparison between the different methods challenging. Longitudinal population-based studies have found an independent association between different LDL subfractions, LDL-P, and an increased risk of cardiovascular events, but definitive evidence that these measurements add predictive value to the standard risk markers is lacking. No studies have proven that these measurements improve clinical outcomes. PCSK9 inhibitors seem to be effective at lowering all LDL subfractions and LDL-P, but any evidence that measuring LDL subfractions and LDL-P yield clinically useful information is lacking. Such analyses are currently not recommended when considering whether to initiate PCKS9 inhibitors in patients at risk of CVD.