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Atherosclerotic Cardiovascular Disease in South Asians in the United States: Epidemiology, Risk Factors, and Treatments: A Scientific Statement From the American Heart Association [AHA Scientific Statements]

Lun, 02/07/2018 - 19:45
South Asians (from Bangladesh, Bhutan, India, the Maldives, Nepal, Pakistan, and Sri Lanka) make up one quarter of the world’s population and are one of the fastest-growing ethnic groups in the United States. Although native South Asians share genetic and cultural risk factors with South Asians abroad, South Asians in the United States can differ in socioeconomic status, education, healthcare behaviors, attitudes, and health insurance, which can affect their risk and the treatment and outcomes of atherosclerotic cardiovascular disease (ASCVD). South Asians have higher proportional mortality rates from ASCVD compared with other Asian groups and non-Hispanic whites, in contrast to the finding that Asian Americans (Asian Indian, Chinese, Filipino, Japanese, Korean, and Vietnamese) aggregated as a group are at lower risk of ASCVD, largely because of the lower risk observed in East Asian populations. Literature relevant to South Asian populations regarding demographics and risk factors, health behaviors, and interventions, including physical activity, diet, medications, and community strategies, is summarized. The evidence to date is that the biology of ASCVD is complex but is no different in South Asians than in any other racial/ethnic group. A majority of the risk in South Asians can be explained by the increased prevalence of known risk factors, especially those related to insulin resistance, and no unique risk factors in this population have been found. This scientific statement focuses on how ASCVD risk factors affect the South Asian population in order to make recommendations for clinical strategies to reduce disease and for directions for future research to reduce ASCVD in this population.

Trends in Hospitalizations and Survival of Acute Decompensated Heart Failure in Four US Communities (2005-2014) [Original Research Article]

Lun, 02/07/2018 - 19:45
Background:Community trends of acute decompensated heart failure (ADHF) in diverse populations may differ by race and sex.Methods:The ARIC study (Atherosclerosis Risk in Communities) sampled heart failure-related hospitalizations (?55 years of age) in 4 US communities from 2005 to 2014 using International Classification of Diseases, Ninth Revision, Clinical Modification codes. ADHF hospitalizations were validated by standardized physician review and computer algorithm, yielding 40?173 events after accounting for sampling design (unweighted n=8746).Results:Of the ADHF hospitalizations, 50% had reduced ejection fraction, and 39% had preserved EF (HFpEF). HF with reduced ejection fraction was more common in black men and white men, whereas HFpEF was most common in white women. Average age-adjusted rates of ADHF were highest in blacks (38.1 per 1000 black men, 30.5 per 1000 black women), with rates differing by HF type and sex. ADHF rates increased over the 10 years (average annual percentage change: black women +4.3%, black men +3.7%, white women +1.9%, white men +2.6%), mostly reflecting more acute HFpEF. Age-adjusted 28-day and 1-year case fatality proportions were ?10% and 30%, respectively, similar across race-sex groups and HF types. Only blacks showed decreased 1-year mortality over time (average annual percentage change: black women –5.4%, black men –4.6%), with rates differing by HF type (average annual percentage change: black women HFpEF –7.1%, black men HF with reduced ejection fraction –4.7%).Conclusions:Between 2005 and 2014, trends in ADHF hospitalizations increased in 4 US communities, primarily driven by acute HFpEF. Survival at 1 year was poor regardless of EF but improved over time for black women and black men.

Heart Failure Epidemic [Editorials]

Lun, 02/07/2018 - 19:45

Long-Term Outcomes of Hypertrophic Cardiomyopathy Diagnosed During Childhood [Original Research Article]

Lun, 02/07/2018 - 19:45
Background:Late survival and symptomatic status of children with hypertrophic cardiomyopathy have not been well defined. We examined long-term outcomes for pediatric hypertrophic cardiomyopathy.Methods:The National Australian Childhood Cardiomyopathy Study is a longitudinal population-based cohort study of children (0–10 years of age) diagnosed with cardiomyopathy between 1987 and 1996. The primary study end point was time to death or cardiac transplantation.Results:There were 80 patients with hypertrophic cardiomyopathy, with a median age at diagnosis of 0.48 (interquartile range, 0.1, 2.5) years. Freedom from death/transplantation was 86% (95% confidence interval [CI], 77.0–92.0) 1 year after presentation, 80% (95% CI, 69.0–87.0) at 10 years, and 78% (95% CI, 67.0–86.0) at 20 years. From multivariable analyses, risk factors for death/transplantation included symmetrical left ventricular hypertrophy at the time of diagnosis (hazard ratio, 4.20; 95% CI, 1.60–11.05; P=0.004), Noonan syndrome (hazard ratio, 2.88; 95% CI, 1.02–8.08; P=0.045), higher posterior wall thickness z score (hazard ratio, 1.45; 95% CI, 1.22–1.73; P<0.001), and lower fractional shortening z score (hazard ratio, 0.84; 95% CI, 0.74–0.95; P=0.005) during follow-up. Nineteen (23%) subjects underwent left ventricular myectomy. At a median of 15.7 years of follow-up, 27 (42%) of 63 survivors were treated with ?-blocker, and 13 (21%) had an implantable cardioverter-defibrillator.Conclusions:The highest risk of death or transplantation for children with hypertrophic cardiomyopathy is within 1 year after diagnosis, with low attrition rates thereafter. Many subjects receive medical, surgical, or device therapy.

Seafood Long-Chain n-3 Polyunsaturated Fatty Acids and Cardiovascular Disease: A Science Advisory From the American Heart Association [AHA Science Advisories]

Lun, 02/07/2018 - 19:45
Since the 2002 American Heart Association scientific statement “Fish Consumption, Fish Oil, Omega-3 Fatty Acids, and Cardiovascular Disease,” evidence from observational and experimental studies and from randomized controlled trials continues to emerge to further substantiate the beneficial effects of seafood long-chain n-3 polyunsaturated fatty acids and cardiovascular disease. A recent American Heart Association science advisory addressed the specific effect of n-3 polyunsaturated fatty acid supplementation on clinical cardiovascular events. This American Heart Association science advisory extends that review and offers further support to include n-3 polyunsaturated fatty acids from seafood consumption. Several potential mechanisms have been investigated, including antiarrhythmic, anti-inflammatory, hematologic, and endothelial, although for most, longer-term dietary trials of seafood are warranted to substantiate the benefit of seafood as a replacement for other important sources of macronutrients. The present science advisory reviews this evidence and makes a suggestion in the context of the 2015–2020 Dietary Guidelines for Americans and in consideration of other constituents of seafood and the impact on sustainability. We conclude that 1 to 2 seafood meals per week be included to reduce the risk of congestive heart failure, coronary heart disease, ischemic stroke, and sudden cardiac death, especially when seafood replaces the intake of less healthy foods.

Oral Anticoagulation in Very Elderly Patients With Atrial Fibrillation [Original Research Article]

Lun, 02/07/2018 - 19:45
Background:Stroke prevention with oral anticoagulants (OACs) is the cornerstone for the management of atrial fibrillation (AF). However, data about the use of OACs among patients ?90 years of age are limited. We aimed to investigate the risk of ischemic stroke and intracranial hemorrhage (ICH) and the net clinical benefit of OAC treatment for very elderly patients with AF (?90 years of age).Methods:This study used the National Health Insurance Research Database in Taiwan. Risks of ischemic stroke and ICH were compared between 11?064 and 14?658 patients with and without AF ?90 years of age without antithrombotic therapy from 1996 to 2011. Patients with AF (n=15?756) were divided into 3 groups (no treatment, antiplatelet agents, and warfarin), and the risks of stroke and ICH were analyzed. The risks of ischemic stroke and ICH were further compared between patients treated with warfarin and nonvitamin K antagonist OACs (NOACs) from 2012 to 2015 when NOACs were available in Taiwan.Results:Compared with patients without AF, patients with AF had an increased risk of ischemic stroke (event number/patient number, incidence = 742/11?064, 5.75%/y versus 1399/14?658, 3.00%/y; hazard ratio, 1.93; 95% confidence interval, 1.74–2.14) and similar risk of ICH (131/11?064, 0.97%/y versus 206/14?658, 0.54%/y; hazard ratio, 0.85; 95% confidence interval, 0.66–1.09) in competing risk analysis for mortality. Among patients with AF, warfarin use was associated with a lower stroke risk (39/617, 3.83%/y versus 742/11?064, 5.75%/y; hazard ratio, 0.69; 95% confidence interval, 0.49–0.96 in a competing risk model), with no difference in ICH risk compared with nontreatment. When compared with no antithrombotic therapy or antiplatelet drugs, warfarin was associated with a positive net clinical benefit. These findings persisted in propensity-matched analyses. Compared with warfarin, NOACs were associated with a lower risk of ICH (4/978, 0.42%/y versus 19/768, 1.63%/y; hazard ratio, 0.32; 95% confidence interval, 0.10–0.97 in a competing risk model), with no difference in risk of ischemic stroke.Conclusions:Among patients with AF ?90 years of age, warfarin was associated with a lower risk of ischemic stroke and positive net clinical benefit. Compared with warfarin, NOACs were associated with a lower risk of ICH. Thus, OACs may still be considered as thromboprophylaxis for elderly patients, with NOACs being the more favorable choice.

Novel Adipokine, FAM19A5, Inhibits Neointima Formation After Injury Through Sphingosine-1-Phosphate Receptor 2 [Original Research Article]

Lun, 02/07/2018 - 19:45
Background:Obesity plays crucial roles in the development of cardiovascular diseases. However, the mechanisms that link obesity and cardiovascular diseases remain elusive. Compelling evidence indicates that adipokines play an important role in obesity-related cardiovascular diseases. Here, we found a new adipokine-named family with sequence similarity 19, member A5 (FAM19A5), a protein with unknown function that was predicted to be distantly related to the CC-chemokine family. We aimed to test whether adipose-derived FAM19A5 regulates vascular pathology on injury.Methods:DNA cloning, protein expression, purification, and N-terminal sequencing were applied to characterize FAM19A5. Adenovirus infection and siRNA transfection were performed to regulate FAM19A5 expression. Balloon and wire injury were performed in vivo on the rat carotid arteries and mouse femoral arteries, respectively. Bioinformatics analysis, radioactive ligand-receptor binding assays, receptor internalization, and calcium mobilization assays were used to identify the functional receptor for FAM19A5.Results:We first characterized FAM19A5 as a secreted protein, and the first 43 N-terminal amino acids were the signal peptides. Both FAM19A5 mRNA and protein were abundantly expressed in the adipose tissue but were downregulated in obese mice. Overexpression of FAM19A5 markedly inhibited vascular smooth muscle cell proliferation and migration and neointima formation in the carotid arteries of balloon-injured rats. Accordingly, FAM19A5 silencing in adipocytes significantly promoted vascular smooth muscle cell activation. Adipose-specific FAM19A5 transgenic mice showed greater attenuation of neointima formation compared with wild-type littermates fed with or without Western-style diet. We further revealed that sphingosine-1-phosphate receptor 2 was the functional receptor for FAM19A5, with a dissociation constant (Kd) of 0.634 nmol/L. Inhibition of sphingosine-1-phosphate receptor 2 or its downstream G12/13-RhoA signaling circumvented the suppressive effects of FAM19A5 on vascular smooth muscle cell proliferation and migration.Conclusions:We revealed that a novel adipokine, FAM19A5, was capable of inhibiting postinjury neointima formation via sphingosine-1-phosphate receptor 2-G12/13-RhoA signaling. Downregulation of FAM19A5 during obesity may trigger cardiometabolic diseases.

Bmal1 in Perivascular Adipose Tissue Regulates Resting-Phase Blood Pressure Through Transcriptional Regulation of Angiotensinogen [Original Research Article]

Lun, 02/07/2018 - 19:45
Background:The perivascular adipose tissue (PVAT) surrounding vessels constitutes a distinct functional integral layer of the vasculature required to preserve vascular tone under physiological conditions. However, there is little information on the relationship between PVAT and blood pressure regulation, including its potential contributions to circadian blood pressure variation.Methods:Using unique brown adipocyte–specific aryl hydrocarbon receptor nuclear translocator-like protein 1 (Bmal1) and angiotensinogen knockout mice, we determined the vasoactivity of homogenized PVAT in aortic rings and how brown adipocyte peripheral expression of Bmal1 and angiotensinogen in PVAT regulates the amplitude of diurnal change in blood pressure in mice.Results:We uncovered a peripheral clock in PVAT and demonstrated that loss of Bmal1 in PVAT reduces blood pressure in mice during the resting phase, leading to a superdipper phenotype. PVAT extracts from wild-type mice significantly induced contractility of isolated aortic rings in vitro in an endothelium-independent manner. This property was impaired in PVAT from brown adipocyte–selective Bmal1-deficient (BA-Bmal1-KO) mice. The PVAT contractile properties were mediated by local angiotensin II, operating through angiotensin II type 1 receptor–dependent signaling in the isolated vessels and linked to PVAT circadian regulation of angiotensinogen. Indeed, angiotensinogen mRNA and angiotensin II levels in PVAT of BA-Bmal1-KO mice were significantly reduced. Systemic infusion of angiotensin II, in turn, reduced Bmal1 expression in PVAT while eliminating the hypotensive phenotype during the resting phase in BA-Bmal1-KO mice. Angiotensinogen, highly expressed in PVAT, shows circadian expression in PVAT, and selective deletion of angiotensinogen in brown adipocytes recapitulates the phenotype of selective deletion of Bmal1 in brown adipocytes. Furthermore, angiotensinogen is a transcriptional target of Bmal1 in PVAT.Conclusions:These data indicate that local Bmal1 in PVAT regulates angiotensinogen expression and the ensuing increase in angiotensin II, which acts on smooth muscle cells in the vessel walls to regulate vasoactivity and blood pressure in a circadian fashion during the resting phase. These findings will contribute to a better understanding of the cardiovascular complications of circadian disorders, alterations in the circadian dipping phenotype, and cross-talk between systemic and peripheral regulation of blood pressure.

Anemia and Iron Deficiency in Heart Failure [In Depth]

Lun, 02/07/2018 - 19:45
Anemia and iron deficiency are important and common comorbidities that often coexist in patients with heart failure. Both conditions, together or independently, are associated with poor clinical status and worse outcomes. Whether anemia and iron deficiency are just markers of heart failure severity or whether they mediate heart failure progression and outcomes and therefore should be treated is not entirely clear. Treatment of anemia in patients with heart failure with erythropoiesis-stimulating agents has been evaluated intensively during the past several years. Unfortunately, these agents did not improve outcomes but were associated with a higher risk of adverse events. Iron deficiency in patients with heart failure can be absolute, when total body iron is decreased, or functional, when total body iron is normal or increased but is inadequate to meet the needs of target tissues because of sequestration in the storage pool. Whereas iron replacement is appropriate in patients with anemia resulting from absolute iron deficiency, it has been unclear whether and how absolute or functional iron deficiency should be treated in nonanemic patients with heart failure. Recently, small studies found that administration of intravenous iron in patients with heart failure and absolute or functional iron deficiency with or without anemia improves symptoms and exercise capacity, but long-term outcomes and safety data are not yet available. In this review, we discuss the causes and pathogenesis of and treatment options for anemia and iron deficiency in patients with heart failure.