Non-alcoholic fatty liver disease (NAFLD) is highly prevalent and includes a spectrum of abnormalities ranging from steatosis to cirrhosis. In this review, we address recent evidence and limitations ...of studies that evaluated the association of NAFLD with atherosclerotic cardiovascular disease. NAFLD is considered an ectopic fat deposit associated with metabolic (insulin resistance, hyperglycemia and dyslipidemia), inflammatory, coagulation and blood pressure disturbances. Prospective studies have associated NAFLD presence and severity, particularly steatohepatitis and fibrosis, with an increased risk of cardiovascular disease. However, these studies are limited by heterogeneity concerning NAFLD diagnostic criteria and disease severity stratification, as well as by the presence of confounding factors. In addition, genetic variants predisposing to NAFLD, such as the PNPLA3 I148M mutation, were not consistently associated with an increased risk of cardiovascular events. Therefore, currently, it is not possible to prove a causal relation between NAFLD and cardiovascular disease. Furthermore, there is presently no evidence that NAFLD diagnosis can be used as a tool to improve cardiovascular risk stratification and modify treatment. Specific treatments for NAFLD are being developed and must be tested prospectively in adequately designed trials to determine the potential of reducing both hepatic and cardiovascular diseases and to prove whether NAFLD is indeed a cause of atherosclerosis.
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•NAFLD is highly prevalent ranging from steatosis to cirrhosis.•NAFLD advanced forms associated with cardiovascular risk.•NAFLD studies limited by heterogeneity and confounders.•Genetic variants predisposing to NAFLD not consistently associated with cardiovascular events.•No proof that NAFLD is causal of cardiovascular disease.
Despite decades of unequivocal evidence that waist circumference provides both independent and additive information to BMI for predicting morbidity and risk of death, this measurement is not ...routinely obtained in clinical practice. This Consensus Statement proposes that measurements of waist circumference afford practitioners with an important opportunity to improve the management and health of patients. We argue that BMI alone is not sufficient to properly assess or manage the cardiometabolic risk associated with increased adiposity in adults and provide a thorough review of the evidence that will empower health practitioners and professional societies to routinely include waist circumference in the evaluation and management of patients with overweight or obesity. We recommend that decreases in waist circumference are a critically important treatment target for reducing adverse health risks for both men and women. Moreover, we describe evidence that clinically relevant reductions in waist circumference can be achieved by routine, moderate-intensity exercise and/or dietary interventions. We identify gaps in the knowledge, including the refinement of waist circumference threshold values for a given BMI category, to optimize obesity risk stratification across age, sex and ethnicity. We recommend that health professionals are trained to properly perform this simple measurement and consider it as an important 'vital sign' in clinical practice.
Findings from epidemiological studies over the past 30 years have shown that visceral adipose tissue, accurately measured by CT or MRI, is an independent risk marker of cardiovascular and metabolic ...morbidity and mortality. Emerging evidence also suggests that ectopic fat deposition, including hepatic and epicardial fat, might contribute to increased atherosclerosis and cardiometabolic risk. This joint position statement from the International Atherosclerosis Society and the International Chair on Cardiometabolic Risk Working Group on Visceral Obesity summarises the evidence for visceral adiposity and ectopic fat as emerging risk factors for type 2 diabetes, atherosclerosis, and cardiovascular disease, with a focus on practical recommendations for health professionals and future directions for research and clinical practice. We discuss the measurement of visceral and ectopic fat, pathophysiology and contribution to adverse health outcomes, response to treatment, and lessons from a public health programme targeting visceral and ectopic fat. We identify knowledge gaps and note the need to develop simple, clinically applicable tools to be able to monitor changes in visceral and ectopic fat over time. Finally, we recognise the need for public health messaging to focus on visceral and ectopic fat in addition to excess bodyweight to better combat the growing epidemic of obesity worldwide.
Pathophysiological, epidemiological, and genetic studies provide strong evidence that lipoprotein(a) Lp(a) is a causal mediator of cardiovascular disease (CVD) and calcific aortic valve disease ...(CAVD). Specific therapies to address Lp(a)-mediated CVD and CAVD are in clinical development. Due to knowledge gaps, the National Heart, Lung, and Blood Institute organized a working group that identified challenges in fully understanding the role of Lp(a) in CVD/CAVD. These included the lack of research funding, inadequate experimental models, lack of globally standardized Lp(a) assays, and inadequate understanding of the mechanisms underlying current drug therapies on Lp(a) levels. Specific recommendations were provided to facilitate basic, mechanistic, preclinical, and clinical research on Lp(a); foster collaborative research and resource sharing; leverage expertise of different groups and centers with complementary skills; and use existing National Heart, Lung, and Blood Institute resources. Concerted efforts to understand Lp(a) pathophysiology, together with diagnostic and therapeutic advances, are required to reduce Lp(a)-mediated risk of CVD and CAVD.
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Homozygous familial hypercholesterolemia (HoFH) is an autosomal co-dominant disease resulting from mutations in both copies of the low-density lipoprotein receptor (LDLR) gene. Mutations in 3 other ...associated genes, proprotein convertase subtilisin/kexin type 9, apolipoprotein B (APOB), and, more rarely, the autosomal recessive hypercholesterolemia adaptor protein, may lead to a similar phenotype with varying severity. HoFH patients have aggressive cardiovascular disease that develops from birth due to severe LDLR defects, resulting, in turn, in excess production of Apo B-containing atherogenic lipoproteins (low-density lipoprotein LDL and lipoprotein(a)). The condition is characterized by exceptionally high LDL cholesterol levels, cutaneous and tendon xanthomas, and valvular and supravalvular stenosis, and accelerated atherosclerosis often manifests in the first 2 decades of life. Treatment typically involves lipid-modifying medical therapy as well as mechanical removal of plasma LDL by means of apheresis. Although statins have afforded survival into the third and fourth decades of life, further therapeutic advancements currently under investigation promise hope of further improvements in survival and improved quality of life. The purpose of this review is to provide current perspectives on diagnosis and therapy in an effort to encourage early recognition and treatment of this rare but severe disease.
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