Best practice & research. Clinical endocrinology & metabolism最新文献

Vitamin D deficiency is one of the most common vitamin deficiencies across different populations. It has primarily been implicated in the development of metabolic bone disease in adults and children. However, in recent years its role in immunomodulation has also emerged and has gained further importance since the occurrence of coronavirus disease 2019 (COVID-19). Here, we describe the most recent literature on vitamin D and its impact on immunomodulatory pathways. Furthermore, the current evidence on the impact of vitamin D deficiency on COVID-19 infection, severity, and prognosis is summarised. We also highlight the key research gaps in this field that need further research.

At the end of 2019, the world began to fight the coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus-2. Many vaccines have quickly been developed to control the epidemic, and with the widespread use of vaccines globally, several vaccine-related adverse events have been reported. This review mainly focused on COVID-19 vaccination-associated thyroiditis and summarized the current evidence regarding vaccine-induced subacute thyroiditis, silent thyroiditis, Graves’ disease, and Graves’ orbitopathy. The main clinical characteristics of each specific disease were outlined, and possible pathophysiological mechanisms were discussed. Finally, areas lacking evidence were specified, and a research agenda was proposed.

Atherosclerotic cardiovascular disease is a leading cause of morbidity and mortality, and statins have become a cornerstone in its treatment and prevention. Despite the well-documented benefits of statins, many patients stop taking them, with adverse muscle symptoms being a commonly cited reason. Although some statin-associated adverse muscle effects are real, some can be attributed to the nocebo effect, which is the patient's perception of harm. The purpose of this article is to review the literature on statin safety, particularly that related to muscle, to analyze adverse effects, and to propose various treatment strategies for the statin intolerant patient.

ANGPTL3 has emerged as a therapeutic target whose inhibition results in profound reductions of plasma lipids, including atherogenic triglyceride-rich lipoproteins and low-density lipoprotein cholesterol. The identification of ANGPTL3 deficiency as a cause of familial combined hypolipidemia in humans hastened the development of anti-ANGPTL3 therapeutic agents, including evinacumab (a monoclonal antibody inhibiting circulating ANGPTL3), vupanorsen (an antisense oligonucleotide [ASO] targeting hepatic ANGPTL3 mRNA for degradation), and others. Advances have also been made in ANGPTL3 vaccination and gene editing strategies, with the former still in preclinical phases and the latter in preparation for Phase 1 trials. Here, we review the discovery of ANGPTL3 as an important regulator of lipoprotein metabolism, molecular characteristics of the protein, mechanisms by which it regulates plasma lipids, and the clinical development of anti-ANGPTL3 agents. The clinical success of therapies inhibiting ANGPTL3 highlights the importance of this target as a novel approach in treating refractory hypertriglyceridemia and hypercholesterolemia.

High levels of lipoprotein(a) [Lp(a)] are causal for development of atherosclerotic cardiovascular disease and highly regulated by genetics. Levels are higher in Blacks compared to Whites, and in women compared to men. Lp(a)’s main protein components are apolipoprotein (apo) (a) and apoB100, the latter being the main component of Low-Density Lipoprotein (LDL) particles. Studies have identified Lp(a) to be associated with inflammatory, coagulation and wound healing pathways. Lack of validated and accepted assays to measure Lp(a), risk cutoff values, guidelines for diagnosis, and targeted therapies have added challenges to the field. Scientific efforts are ongoing to address these, including studies evaluating the cardiovascular benefits of decreasing Lp(a) levels with targeted apo(a) lowering treatments. This review will provide a synopsis of evidence-based effects of high Lp(a) on disease presentation, highlight available guidelines and discuss promising therapies in development. We will conclude with current clinical information and future research needs in the field.

Endocrine diseases may be associated with dyslipidaemia and may increase atherosclerotic cardiovascular disease (ASCVD) risk. This chapter describes changes in lipids and lipoproteins in diseases of the pituitary, thyroid, adrenal glands, ovaries, and testes, the mechanisms for these changes, ASCVD risk in these endocrine disorders, and whether treatment of the endocrine disorder improves the lipid profile and reduces ASCVD risk. Acromegaly, GH deficiency, Cushing syndrome, chronic glucocorticoid replacement, hypothyroidism, PCOS and male hypogonadism can increase LDL-C and/or TG. Marked reductions in LDL-C are associated with hyperthyroidism, and extremely low HDL-C levels with testosterone and/or other anabolic steroid abuse. Acromegaly, GH deficiency, Cushing syndrome, and chronic glucocorticoid replacement are associated with increased ASCVD risk. Treatment of acromegaly, GH deficiency, hypothyroidism, Cushing syndrome, and testosterone deficiency reduce LDL-C, although statin therapy may still be needed. Effects on ASCVD are not known.

Elevated low-density lipoprotein cholesterol (LDL-C) levels increase the risk of atherosclerotic cardiovascular disease (ASCVD) and lowering LDL-C levels reduces the risk of ASCVD. In patients with elevated LDL-C levels it is important to consider whether lifestyle, other medical conditions, medications, or genetic factors could be causing or contributing to the elevation. There are guidelines from various organizations outlining the approach to lowering LDL-C levels but while these guidelines agree on many issues there are numerous areas where recommendations are discordant. In this review, we outline several principles that will help in deciding who and how to treat patients with elevated LDL-C levels. Specifically, we discuss evidence indicating that the sooner one initiates therapy the better and the greater the reduction in LDL-C the better. Additionally, the higher the LDL-C level and the higher the risk of ASCVD, the greater the benefits of treatment. Using these principles will help in making decisions regarding the treatment of LDL-C levels.

The high density lipoprotein (HDL) fraction of human plasma consists of multiple subpopulations of spherical particles that are structurally uniform, but heterogeneous in terms of size, composition and function. Numerous epidemiological studies have established that an elevated high density lipoprotein cholesterol (HDL-C) level is associated with decreased cardiovascular risk. However, with several recent randomised clinical trials of HDL-C raising agents failing to reduce cardiovascular events, contemporary research is transitioning towards clinical development of the cardioprotective functions of HDLs and the identification of functions that can be exploited for treatment of other diseases. This review describes the origins of HDLs and the causes of their compositional and functional heterogeneity. It then summarises current knowledge of how cardioprotective and other functions of HDLs are regulated. The final section of the review summarises recent advances in the clinical development of HDL-targeted therapies.

Elevated triglyceride levels increase the risk of arteriosclerotic cardiovascular disease (ASCVD) and severely elevated triglyceride levels also increase the risk of triglyceride-induced pancreatitis. Although substantially reducing triglyceride levels will prevent pancreatitis, whether lowering triglycerides per se will reduce CVD risk is unclear. In this review, we outline several principles that will help in deciding who and how to treat patients with elevated triglyceride levels in order to prevent both ASCVD and pancreatitis. Using these principles will help in making decisions regarding the treatment of elevated triglyceride levels.