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.

HDL: o yin-yang da doença cardiovascular / HDL: the yin-yang of cardiovascular disease

Estudos epidemiológicos mostram relação inversa entre níveis plasmáticos de HDL-colesterol (HDL-C) e incidência de doença cardiovascular (DCV). O papel antiaterogênico da HDL é atribuído às suas atividades anti-inflamatória, antitrombótica e antioxidante, além de sua participação no transporte reverso de colesterol (TRC), processo pelo qual a HDL remove colesterol dos tecidos periféricos, incluindo macrófagos da íntima arterial, e o transporta para o fígado para ser excretado pela bile. Com base nesses fatos, o HDL-C tornou-se alvo atrativo para a prevenção da DCV. No entanto, o fracasso do torcetrapib, droga que aumenta substancialmente os níveis de HDL-C, em prevenir DCV, além do conhecimento gerado por estudos de modelos animais e doenças monogênicas que afetam a concentração de HDL-C, tem suscitado questionamentos sobre o papel antiaterogênico da HDL. Esta revisão tem como objetivo abordar aspectos atuais do conhecimento da HDL, baseando-se nessas recentes controvérsias.

Epidemiological studies demonstrate an inverse correlation between plasma HDL-cholesterol (HDL-C) concentration and incidence of cardiovascular disease (CVD). The antiatherogenic role of HDL has been attributed to its anti-inflammatory, antithrombotic and antioxidant properties, besides its participation in the reverse cholesterol transport (RCT), whereby cholesterol from peripheral tissues (including macrophages of the arterial intima) is delivered to the liver for excretion in bile. Due to these actions, HDL-C has evolved as an attractive target for prevention of CVD. However, the failure of torcetrapib, drug that substantially increases HDL-C levels, in preventing CVD and data from studies with animal models and with carriers of monogenic disorders affecting HDL-C levels in humans provide conflicting data about HDL being antiatherogenic. This review addresses the current state of knowledge regarding HDL based on these recent controversies.

A case of Tangier disease with two novel mutations in the ATP-binding cassette transporter A1 gene / 대한내과학회지

Tangier disease (TD) is a rare autosomal recessive disorder of lipoprotein metabolism characterized by extremely low levels of high-density lipoprotein cholesterol (HDL-C) and apolipoprotein (apo) A-I resulting in accumulation of cholesterol esters in various organs. TD is caused by mutations in the ATP-binding cassette transporter A1 (ABCA1) gene. Here, we present the first case report of a Korean patient with TD. A 45-year-old man had corneal opacity, intestinal mucosa abnormalities, and extremely low levels of HDL-C (1.8 mg/dL) and apo A-I (T (p.G1050X) nonsense mutation and c.3202C>T (p.R1068C) missense mutation. The c.3202C>T mutation was not found in 192 normal control alleles.