Very low HDL levels: clinical assessment and management

Abstract

In individuals with very low high-density lipoprotein (HDL-C) cholesterol, such as Tangier disease, LCAT deficiency, and familial hypoalphalipoproteinemia, there is an increased risk of premature atherosclerosis. However, analyzes based on comparisons of populations with small variations in HDL-C mediated by polygenic alterations do not confirm these findings, suggesting that there is an indirect association or heterogeneity in the pathophysiological mechanisms related to the reduction of HDL-C. Trials that evaluated some of the HDL functions demonstrate a more robust degree of association between the HDL system and atherosclerotic risk, but as they were not designed to modify lipoprotein functionality, there is insufficient data to establish a causal relationship. We currently have randomized clinical trials of therapies that increase HDL-C concentration by various mechanisms, and this HDL-C elevation has not independently demonstrated a reduction in the risk of cardiovascular events. Therefore, this evidence shows that (a) measuring HDL-C as a way of estimating HDL-related atheroprotective system function is insufficient and (b) we still do not know how to increase cardiovascular protection with therapies aimed at modifying HDL metabolism. This leads us to a greater effort to understand the mechanisms of molecular action and cellular interaction of HDL, completely abandoning the traditional view focused on the plasma concentration of HDL-C. In this review, we will detail this new understanding and the new horizon for using the HDL system to mitigate residual atherosclerotic risk.

High residual cardiovascular risk after lipid-lowering: prime time for Predictive, Preventive, Personalized, Participatory, and Psycho-cognitive medicine

“…Besides ApoA-I, other HDL components, such as HDL-associated hydrolases (e.g., paraoxonase-1), certain (lyso)phospholipids, nutrition, smoking, air pollution, and plastic-associated chemicals influence HDL’s functionality ( 38 ). In individuals with very low HDL-C, due to rare monogenic dyslipidemia (e.g., Tangier disease, LCAT deficiency, familial hypoalphalipoproteinemia) or due to secondary dyslipidemias, the very low HDL-C levels are associated with (1) increased risk of CVD, (2) comorbidities, such as T2DM, and (3) elevated levels of sdLDL ( 39 ).…”

Expression analysis of ABCA1 in type 2 diabetic Pakistani patients with and without dyslipidemia and correlation with glycemic index and lipid profile

“…Our study findings couldn't establish a positive correlation of TAGs with that of gene expression in deranged lipid and diabetic subjects while a significant difference was observed in levels of triglycerides with that of diabetics in a study 33 . The prevalence of dyslipidemia has been observed to be increased in 60-70% patients of type www.nature.com/scientificreports/ II diabetes mellitus, being low HDL level dominant in worsening the glucose tolerance among diabetics 34,35 . A study conducted on Pakistani population reported that lipid parameters are alarmingly high in type 2 diabetes mellitus specially among the newly diagnosed ones 36 .…”

A decreased level of high‐density lipoprotein is a possible risk factor for type 2 diabetes mellitus: A review

“…According to studies done on different populations, 18.7% of individuals with very low HDL‐C levels carry rare genetic variants of great effect and 19.3% carry common low‐effect variants 43 . Thus, the genetic basis of low HDL‐C levels is often regarded as polygenic 44 …”