Risk Of Cardiovascular Disease In Patients Research Articles

Impact of Biological Agents on Imaging and Biomarkers of Cardiovascular Disease in Patients with Psoriasis: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials

The effect of biologics on the risk for cardiovascular disease in patients with psoriasis is still unclear despite their widespread use. The objective of this study was to examine the impact of licensed biological therapies on imaging and biomarkers of cardiovascular disease risk in patients with psoriasis by a systematic review and meta-analysis of placebo-controlled trials. A comprehensive search of studies published before 1 June 2020 was performed in Medline-Ovid, EMBASE, and CENTRAL using a predefined strategy to identify relevant articles. Five studies were included for the final examination, and two studies were included in the meta-analysis. We did not find a significant reduction in aortic vascular inflammation in patients treated with adalimumab compared with those who received placebo at weeks 12-16. There was no beneficial effect on imaging biomarkers (aortic vascular inflammation or flow-mediated dilatation) of cardiovascular disease risk in patients exposed to biological therapies (adalimumab and secukinumab) compared with those exposed to placebo, except for ustekinumab showing a reduction in aortic vascular inflammation at week 12 but not at week 52 after the open-label extension period. The strongest reduction in blood-based cardiometabolic risk biomarkers was observed with adalimumab (CRP, TNF-α, IL-6, and GlycA) and phototherapy (CRP and IL-6) compared with that observed with placebo. Randomized controlled trials show that ustekinumab reduces aortic vascular inflammation and that TNF-α inhibitors and phototherapy reduce CRP and IL-6. These surrogate marker findings require randomized controlled trials evaluating cardiovascular events to inform clinical practice.

Development and validation of optimal phenomapping methods to estimate long-term atherosclerotic cardiovascular disease risk in patients with type 2 diabetes.

Type 2 diabetes is a heterogeneous disease process with variable trajectories of CVD risk. We aimed to evaluate four phenomapping strategies and their ability to stratify CVD risk in individuals with type 2 diabetes and to identify subgroups who may benefit from specific therapies. Participants with type 2 diabetes and free of baseline CVD in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial were included in this study (N = 6466). Clustering using Gaussian mixture models, latent class analysis, finite mixture models (FMMs) and principal component analysis was compared. Clustering variables included demographics, medical and social history, laboratory values and diabetes complications. The interaction between the phenogroup and intensive glycaemic, combination lipid and intensive BP therapy for the risk of the primary outcome (composite of fatal myocardial infarction, non-fatal myocardial infarction or unstable angina) was evaluated using adjusted Cox models. The phenomapping strategies were independently assessed in an external validation cohort (Look Action for Health in Diabetes [Look AHEAD] trial: n = 4211; and Bypass Angioplasty Revascularisation Investigation 2 Diabetes [BARI 2D] trial: n = 1495). Over 9.1years of follow-up, 789 (12.2%) participants had a primary outcome event. FMM phenomapping with three phenogroups was the best-performing clustering strategy in both the derivation and validation cohorts as determined by Bayesian information criterion, Dunn index and improvement in model discrimination. Phenogroup 1 (n = 663, 10.3%) had the highest burden of comorbidities and diabetes complications, phenogroup 2 (n = 2388, 36.9%) had an intermediate comorbidity burden and lowest diabetes complications, and phenogroup 3 (n = 3415, 52.8%) had the fewest comorbidities and intermediate burden of diabetes complications. Significant interactions were observed between phenogroups and treatment interventions including intensive glycaemic control (p-interaction = 0.042) and combination lipid therapy (p-interaction < 0.001) in the ACCORD, intensive lifestyle intervention (p-interaction = 0.002) in the Look AHEAD and early coronary revascularisation (p-interaction = 0.003) in the BARI 2D trial cohorts for the risk of the primary composite outcome. Favourable reduction in the risk of the primary composite outcome with these interventions was noted in low-risk participants of phenogroup 3 but not in other phenogroups. Compared with phenogroup 3, phenogroup 1 participants were more likely to have severe/symptomatic hypoglycaemic events and medication non-adherence on follow-up in the ACCORD and Look AHEAD trial cohorts. Clustering using FMMs was the optimal phenomapping strategy to identify replicable subgroups of patients with type 2 diabetes with distinct clinical characteristics, CVD risk and response to therapies.

Serum Metabolomic Signatures Can Predict Subclinical Atherosclerosis in Patients With Systemic Lupus Erythematosus.

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Herbal or Dietary Supplement Use and Hypertensive Medications: Does the Combination Relate to Medication Adherence and Blood Pressure Control?

Introduction: Medication nonadherence contributes to poor blood pressure control and increases cardiovascular disease risk in patients with hypertension. Identifying modifiable risk factors for low or nonadherence to antihypertensive medication is needed. Studies that have examined the relationship between herbal or dietary supplement (HDS) use and antihypertensive medication nonadherence provide inconsistent findings. Data from the National Health and Nutrition Examination Survey were used to examine the association between HDS use, current use of prescribed antihypertensive medication, and blood pressure status. Methods: The study sample included hypertensive adults (n = 5,478) who have been told by a health professional to take prescribed medication for their health condition. Respondents were classified as either HDS users or HDS nonusers. Depending on the kind of supplement used, HDS users were further divided into three mutually exclusive groups: hypertension HDS users, nonhypertension HDS users, and those who used both kinds of supplements. Supplements groupings were based on reports in the literature. Blood pressure status definition was based on Eighth Joint National Committee (JNC 8) recommendations. Adjusted odds ratios (aORs) and 95% confidence intervals (95% CIs) were obtained from logistic models. Results: Overall HDS use prevalence was 62%. Current medication use did not significantly differ between patients reporting no HDS use and those reporting HDS use (aOR: 1.45; 95% CI: 0.78-2.69). No observable differences were found in current medication use between patients reporting no HDS use and those taking nonhypertension HDS or both kinds of supplements. Use of hypertension HDS was associated with improved blood pressure (aOR: 1.90; 95% CI: 1.07-3.36) compared with no HDS use. Conclusion: In a nationally representative U.S. sample, HDS use did not compromise current use of prescribed medication and was associated with improved blood pressure control. More research is needed to better understand why HDS use is associated with better blood pressure control.

Impact of a 2-year trial of nutritional ketosis on indices of cardiovascular disease risk in patients with type 2 diabetes

BackgroundWe have previously reported that in patients with type 2 diabetes (T2D) consumption of a very low carbohydrate diet capable of inducing nutritional ketosis over 2 years (continuous care intervention, CCI) resulted in improved body weight, glycemic control, and multiple risk factors for cardiovascular disease (CVD) with the exception of an increase in low density lipoprotein cholesterol (LDL-C). In the present study, we report the impact of this intervention on markers of risk for atherosclerotic cardiovascular disease (CVD), with a focus on lipoprotein subfraction particle concentrations as well as carotid-artery intima-media thickness (CIMT).MethodsAnalyses were performed in patients with T2D who completed 2 years of this study (CCI; n = 194; usual care (UC): n = 68). Lipoprotein subfraction particle concentrations were measured by ion mobility at baseline, 1, and 2 years and CIMT was measured at baseline and 2 years. Principal component analysis (PCA) was used to assess changes in independent clusters of lipoprotein particles.ResultsAt 2 years, CCI resulted in a 23% decrease of small LDL IIIb and a 29% increase of large LDL I with no change in total LDL particle concentration or ApoB. The change in proportion of smaller and larger LDL was reflected by reversal of the small LDL subclass phenotype B in a high proportion of CCI participants (48.1%) and a shift in the principal component (PC) representing the atherogenic lipoprotein phenotype characteristic of T2D from a major to a secondary component of the total variance. The increase in LDL-C in the CCI group was mainly attributed to larger cholesterol-enriched LDL particles. CIMT showed no change in either the CCI or UC group.ConclusionConsumption of a very low carbohydrate diet with nutritional ketosis for 2 years in patients with type 2 diabetes lowered levels of small LDL particles that are commonly increased in diabetic dyslipidemia and are a marker for heightened CVD risk. A corresponding increase in concentrations of larger LDL particles was responsible for higher levels of plasma LDL-C. The lack of increase in total LDL particles, ApoB, and in progression of CIMT, provide supporting evidence that this dietary intervention did not adversely affect risk of CVD.

Hypoglycaemia and Cardiovascular Disease Risk in Patients with Diabetes.

Hypoglycaemia represents an important side effect of insulin therapy and insulin secretagogues. It can occur in both type 1 and type 2 diabetes mellitus patients. Also, some associations between hypoglycaemia and cardiovascular (CV) risk have been reported. Several mechanisms may be involved, including the sympathoadrenal system, hypokalaemia, endothelial dysfunction, coagulation, platelets, inflammation, atherothrombosis and impaired autonomic cardiac reflexes. This narrative review discusses the associations of hypoglycaemia with CV diseases, including coronary heart disease (CHD), cardiac arrhythmias, stroke, carotid disease and peripheral artery disease (PAD), as well as with dementia. Severe hypoglycaemia has been related to CHD, CV and all-cause mortality. Furthermore, there is evidence supporting an association between hypoglycaemia and cardiac arrhythmias, potentially predisposing to sudden death. The data linking hypoglycaemia with stroke, carotid disease and PAD is limited. Several factors may affect the hypoglycaemia-CV relationships, such as the definition of hypoglycaemia, patient characteristics, co-morbidities (including chronic kidney disease) and antidiabetic drug therapy. However, the association between hypoglycaemia and dementia is bilateral. Both the disorders are more common in the elderly; thus, glycaemic goals should be carefully selected in older patients. Further research is needed to elucidate the impact of hypoglycaemia on CV disease.

Targeting multiple domains of residual cardiovascular disease risk in patients with diabetes.

There has been a recent resurgence of diabetes-related cardiovascular complications after years of steady improvement. This review highlights established and emerging contemporary secondary prevention approaches that lower the risk of atherosclerotic and nonatherosclerotic cardiovascular disease events among patients with diabetes. Secondary prevention therapies modify residual risk targets, including cardiometabolic pathways, lipoproteins, thrombosis, and inflammation. Large-scale clinical trials of sodium-glucose cotransporter-2 inhibitors have demonstrated significant reductions in hospitalization for heart failure. Glucagon-like peptide-1 receptor agonists have reduced the risk of major adverse cardiovascular events. Recent clinical trials provide evidence supporting the use of nonstatin lipid-lowering therapies, novel antiplatelet and anticoagulant strategies, and antiinflammatory strategies in select cases. Therapeutic approaches targeting multiple distinct pathways have been shown to improve cardiometabolic risk in diabetes. Individual patient characteristics and consideration of residual risk targets may help guide selection of comprehensive secondary prevention approaches.

Product of Serum Calcium and Phosphorus (Ca x Pi) as a Predictor of Cardiovascular Disease Risk in Patients with Chronic Kidney Disease

INTRODUCTION: Most of the chronic kidney disease (CKD) patients develop cardiovascular disease (CVD) in their later stages. Various traditional CVD risk factors are highly prevalent in CKD but mortality of these patients cannot be fully justified by these CVD markers. So this study was designed to determine serum calcium and phosphorus product (Ca×Pi) to predict CVD risk in CKD patients.&#x0D; MATERIAL AND METHODS We followed the guidelines of NKF-KDOQI for CKD diagnosis and staging. Further the patients were classified into 3 different groups based on Ca×Pi product; &lt;40 mg2/dl2 (group 1), 40-55 mg2/dl2 (group 2) and &gt;55 mg2/dl2 (group 3). We then evaluated CVD risk by various traditional risk factors like age, BMI, BP, smoking history, dyslipidemia, previous history of CVD, LVH, arrhythmia, VHD, cardiomyopathy, and IHD.&#x0D; RESULTS: Higher level of Ca×Pi was associated with presence of LVH (32.30% in group 1, 31.42% in group 2 and 46.66% in group 3), Arrythemia (13.84% in group 1, 28.57% in group 2 and 46.67% in group 3), VHD (5.71% in group 2 and 10.00% in group 3), Cardiomyopathy (1.53% in group 1, 8.57% I group 2 and 6.66% in group 3), IHD (6.15% in group1, 11.42% in group 2 and 13.33% in group 3) and hypercholesterolemia, hypertriglyceridemia and increased LDLc.&#x0D; CONCLUSION: This study found that higher Ca×Pi increases with decline in glomerular filtration rate (GFR) and associated with CVD risks and CVD. So, this study raise a potential need to evaluate the level of calcium and phosphorus in all CKD patients and the level should be monitored more thoroughly to prevent CVD.

Effect of saroglitazar 2\xa0mg and 4\xa0mg on glycemic control, lipid profile and cardiovascular disease risk in patients with type 2 diabetes mellitus: a 56-week, randomized, double blind, phase 3 study (PRESS XII study)

BackgroundThe potential for PPAR agonists to positively affect risk of cardiovascular disease in patients with type 2 diabetes (T2DM) is of persistent attention. The PRESS XII study primarily aimed to evaluate the efficacy and safety of saroglitazar (2 mg and 4 mg) as compared to pioglitazone 30 mg on glycemic control in patients with type 2 diabetes mellitus.MethodsIn this randomized double-blind study, patients with T2DM [glycosylated hemoglobin (HbA1c) ≥ 7.5%] were enrolled from 39 sites in India. Patients received once-daily doses of either saroglitazar or pioglitazone (1:1:1 allocation ratio) for a total of 24 weeks. Patients were continued in a double blind extension period for an additional 32 weeks. Efficacy evaluations of glycemic parameters [HbA1c (Primary endpoint at week 24), FPG and PPG] and other lipid parameters (TG, LDL-C, VLDL-C, HDL-C, TC, Non HDL-C, Apo A1 and Apo B) were conducted at week 12, 24 and 56 and compared to the baseline levels. The efficacy analyses were performed by using paired t-test and ANCOVA model.ResultsA total of 1155 patients were enrolled in this study. The baseline characteristics were similar between the three treatment groups. The within group mean (± SD) change in HbA1c (%) from baseline of the saroglitazar (2 mg and 4 mg) and pioglitazone treatment groups at week 24 were: − 1.38 ± 1.99 for saroglitazar 2 mg; − 1.47 ± 1.92 for saroglitazar 4 mg and − 1.41 ± 1.86 for pioglitazone, respectively. Statistically significant reduction from baseline in HbA1c was observed in each treatment group at week 24 with p-value < 0.016. There was a significant reduction in TG, LDL-C, VLDL-C, TC and Non HDL-C with a significant increase in HDL-C from baseline levels (< 0.016). Most of the AE’s were ‘mild’ to ‘moderate’ in severity and were resolved by the completion of the study.ConclusionsSaroglitazar effectively improved glycemic control and lipid parameters over 56 weeks in patients of T2DM receiving background metformin therapy and has a promising potential to reduce the cardiovascular risk in T2DM patients.Trial registration CTRI/2015/09/006203, dated 22/09/2015

1094-P: Short-Acting Exenatide and Markers of Cardiovascular Disease in Type 1 Diabetes: A Randomized, Double-Blinded, Placebo-Controlled Trial

In type 2 diabetes, some glucagon-like peptide 1 receptor agonists (GLP-1RAs) reduce the risk of major adverse cardiovascular events. Whether GLP-1RAs have any effect on cardiovascular disease risk in patients with type 1 diabetes remains to be elucidated. We tested the effect of adding the short-acting GLP-1RA exenatide to insulin treatment on markers of cardiovascular risk in type 1 diabetes. In a randomized, double-blinded, parallel-group trial, 108 individuals with type 1 diabetes aged ≥18 years on multiple daily insulin injection therapy with body mass index &amp;gt;22.0 kg/m2 and HbA1c 7.5-10.0% (59-88 mmol/mol) were randomized (1:1) to preprandial subcutaneous injection of 10 µg exenatide (Byetta®) or placebo three times daily over 26 weeks as add-on treatment to existing insulin therapy. Reported data were secondary endpoints and analyzed in a baseline-adjusted linear mixed model in the intention-to-treat population. Exenatide changed total fat mass by -2.6 kg (95% CI -3.6;-1.6, P&amp;lt;0.0001) and lean body mass by -1.1 kg (95% CI -1.9;-0.4, P=0.01) compared to placebo as assessed by dual-energy X-ray absorptiometry. Central and peripheral fat mass reductions were similar. Exenatide did not change levels of interleukin 2 or 6; tumor necrosis factor alpha; C-reactive protein; N-terminal prohormone of brain natriuretic peptide; or 8-oxo-7,8-dihydroguanosine (RNA oxidation marker) and 8-oxo-7,8-dihydro-2’-deoxyguanosine (DNA oxidation marker). Exenatide added to insulin therapy in type 1 diabetes for 26 weeks resulted in body weight loss primarily from fat mass reduction but had no effect on circulating biomarkers of cardiovascular disease risk. Disclosure N.J. Johansen: Research Support; Self; AstraZeneca. T.F. Dejgaard: Advisory Panel; Self; Novo Nordisk A/S. Consultant; Self; Boehringer Ingelheim International GmbH, Novo Nordisk A/S. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk A/S. A. Lund: Speaker’s Bureau; Self; AstraZeneca, Novo Nordisk A/S, Sanofi. C. Schlüntz: None. E. Larsen: Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc. H.E. Poulsen: Research Support; Self; Boehringer Ingelheim International GmbH. J.P. Gøtze: None. H. Møller: None. T. Vilsbøll: Advisory Panel; Self; AstraZeneca, Mundipharma International, Novo Nordisk A/S, Sun Pharmaceutical Industries Ltd. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Medscape, Merck Sharp &amp; Dohme Corp., Sanofi. H.U. Andersen: Advisory Panel; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. F.K. Knop: Advisory Panel; Self; AstraZeneca, Merck Sharp &amp; Dohme Corp., Mundipharma International, Novo Nordisk A/S, Sanofi. Consultant; Self; Carmot Therapeutics, Inc., Eli Lilly and Company, Novo Nordisk A/S. Research Support; Self; AstraZeneca, Gubra, Novo Nordisk A/S, Sanofi, Zealand Pharma A/S. Speaker’s Bureau; Self; AstraZeneca, Lupin Pharmaceuticals, Inc., Merck Sharp &amp; Dohme Corp., Norgine B.V., Novo Nordisk A/S. Funding AstraZeneca

1417-P: Lipoprotein(a)-Associated Residual Atherosclerotic Cardiovascular Disease Risk in Patients with Cardiovascular Disease on Statin Therapy by Diabetes Status

Background: The relation between elevated lipoprotein(a) [Lp(a)] and future atherosclerotic cardiovascular disease (ASCVD) in those with vs. without diabetes mellitus (DM) but known cardiovascular disease (CVD) is not clear. We examined recurrent ASCVD event risk by DM status in persons with known CVD on statin therapy. Methods: We studied 1,354 patients with and 2,005 patients without DM, all with prior CVD on statin therapy in the AIM-HIGH cohort. First and total recurrent ASCVD event rates were calculated by Lp(a) levels and the PWP model provided hazard ratios (HRs) for events over a mean follow-up of 3.3 years, adjusted for age, sex, trial treatment, LDL-C, and other risk factors. Results: ASCVD event rates (per 1000 person years) increased with Lp(a) levels ranging from &amp;lt;15 mg/dl to ≥70 mg/dL in non-DM: 39.7 to 74.1 for first and 48.5 to 87.3 for total recurrent events and in DM: 51.1 to 79.5 for first and 69.8 to 100.3 for total recurrent events. The Table shows HRs by Lp(a) categories for first and total recurrent ASCVD events. A higher risk for first recurrent events is noted at lower Lp(a) levels in those with vs. without DM. Conclusions: Higher Lp(a) levels predict residual ASCVD risk. However, ASCVD event risk may occur at lower levels of Lp(a) in those with vs. without DM. Future investigations in larger cohorts are needed to confirm these findings. Disclosure Y. Zhao: None. J.C. Sung: Employee; Self; Novartis Pharmaceuticals Corporation. A. Browne: Employee; Self; Novartis Pharmaceuticals Corporation. N.D. Wong: Advisory Panel; Self; Esperion Therapeutics, Inc. Research Support; Self; Amarin Corporation, Amgen, Boehringer Ingelheim Pharmaceuticals, Inc., Novartis AG, Novo Nordisk Inc. Speaker’s Bureau; Self; Amarin Corporation, Sanofi.

Association between IL-1beta and cardiovascular disease risk in patients with newly diagnosed, drug-naïve type 2 diabetes mellitus: a cross-sectional study.

BackgroundTo determine whether the pro-inflammatory cytokine interleukin (IL)-1beta, as a marker of the nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation, can be used to predict cardiovascular disease (CVD) risk in patients with newly diagnosed, drug-naïve type 2 diabetes mellitus (T2DM).MethodsA total of 110 subjects with no history of diabetes were enrolled and divided into control subjects (non-DM group, n=52) and patients with newly diagnosed, drug-naïve T2DM (DM group, n=58).ResultsSerum IL-1beta levels were not different between the two groups. The Framingham CVD risk score (F-score) was positively correlated with the serum IL-1beta level in the DM group. Multivariate regression analyses showed that the F-score was independently associated with the serum IL-1beta level in the DM group. Patients with an intermediate to high CVD risk (F-score ≥10%) also had significantly higher serum IL-1beta levels than did those with a low CVD risk (F-score <5%). Smokers in the DM group had higher IL-1beta levels than did those in the non-DM group, regardless of the F-score.ConclusionsThese results suggest that serum IL-1beta levels might be useful as an independent risk factor predicting CVD risk in patients with newly diagnosed, drug naïve T2DM, particularly those who smoke.

Evaluation of systo-diastolic cardiac function and arterial stiffness in subjects with new diagnosis of coeliac disease without cardiovascular risk factors.

In literature, there are conflicting opinions on the development of cardiovascular disease risk in patients with coeliac disease (CD). The aim of the research was to identify in young subjects without cardiovascular risk factor and newly diagnosed CD, alterations in different instrumental parameters that are associated with an augmented cardiovascular risk. Twenty-one consecutive young adults with a new diagnosis of CD and without cardiovascular risk factors were prospectively enrolled and underwent transthoracic echocardiography to analyse ascending aorta elastic properties [including tissue Doppler imaging strain (TDI-ε)] and left ventricular 2D strains (global longitudinal, radial and circumferential), and applanation tonometry by SphygmoCor. Cases were compared with 21 age- and sex-matched healthy controls. Mean age of the cases was 38 ± 9years and 15 of them (71%) were female. Brachial and central blood pressure was higher in the CD group. Elastic properties of the ascending aorta were all impaired in the CD group: TDI-ε was altered in 57% of cases (0% of controls, p < 0.001). Concentric remodelling and grade I diastolic dysfunction were present in 38% and 24% of cases, respectively (0% of controls, p < 0.001). Global longitudinal strain was normal in all subjects, while radial and circumferential strain were altered in 67% and 35%, respectively (0% of controls, p < 0.001). In young subjects without cardiovascular risk factor, a newly diagnosed CD is associated with altered aortic elastic properties, left ventricular concentric remodelling and diastolic dysfunction and altered radial and circumferential strain.

Sex and racial differences in cardiovascular disease risk in patients with atrial fibrillation.

BackgroundOutcomes among atrial fibrillation (AF) patients may differ according to race/ethnicity and sex due to differences in biology, the prevalence of cardiovascular risk factors, and the use and effectiveness of AF treatments. We aimed to characterize patterns of cardiovascular risk across subgroups of AF patients by sex and race/ethnicity, since doing so may provide opportunities to identify interventions. We also evaluated whether these patterns changed over time.MethodsWe utilized administrative claims data from the Optum Clinformatics® Datamart database from 2009 to 2015. Patients with AF with ≥6 months of enrollment prior to the first non-valvular AF diagnosis were included in the analysis. Final analysis utilized Cox proportional hazard models to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI) for cardiovascular outcomes stratified by sex and race/ethnicity. An additional analysis stratified outcomes by calendar year of AF diagnosis to evaluate changes in outcomes over time.ResultsIn a cohort of 380,636 AF patients, women had a higher risk of ischemic stroke [HR (95% CI): 1.25 (1.19, 1.31)] and lower risk of heart failure and myocardial infarction [HR (95% CI): 0.91 (0.88, 0.94) and 0.81 (0.77, 0.86), respectively)] compared to men. Black patients had elevated risk across all endpoints compared to whites, while Hispanics and Asian Americans showed no significant differences in any outcome compared to white patients. These sex and race/ethnic differences did not change over time.ConclusionsWe found sex and race/ethnic differences in risk of cardiovascular outcomes among AF patients, without evidence of improvement over time.

Omega-3 Fatty Acids for the Management of Hypertriglyceridemia: A Science Advisory From the American Heart Association.

Hypertriglyceridemia (triglycerides 200-499 mg/dL) is relatively common in the United States, whereas more severe triglyceride elevations (very high triglycerides, ≥500 mg/dL) are far less frequently observed. Both are becoming increasingly prevalent in the United States and elsewhere, likely driven in large part by growing rates of obesity and diabetes mellitus. In a 2002 American Heart Association scientific statement, the omega-3 fatty acids (n-3 FAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were recommended (at a dose of 2-4 g/d) for reducing triglycerides in patients with elevated triglycerides. Since 2002, prescription agents containing EPA+DHA or EPA alone have been approved by the US Food and Drug Administration for treating very high triglycerides; these agents are also widely used for hypertriglyceridemia. The purpose of this advisory is to summarize the lipid and lipoprotein effects resulting from pharmacological doses of n-3 FAs (>3 g/d total EPA+DHA) on the basis of new scientific data and availability of n-3 FA agents. In treatment of very high triglycerides with 4 g/d, EPA+DHA agents reduce triglycerides by ≥30% with concurrent increases in low-density lipoprotein cholesterol, whereas EPA-only did not raise low-density lipoprotein cholesterol in very high triglycerides. When used to treat hypertriglyceridemia, n-3 FAs with EPA+DHA or with EPA-only appear roughly comparable for triglyceride lowering and do not increase low-density lipoprotein cholesterol when used as monotherapy or in combination with a statin. In the largest trials of 4 g/d prescription n-3 FA, non-high-density lipoprotein cholesterol and apolipoprotein B were modestly decreased, indicating reductions in total atherogenic lipoproteins. The use of n-3 FA (4 g/d) for improving atherosclerotic cardiovascular disease risk in patients with hypertriglyceridemia is supported by a 25% reduction in major adverse cardiovascular events in REDUCE-IT (Reduction of Cardiovascular Events With EPA Intervention Trial), a randomized placebo-controlled trial of EPA-only in high-risk patients treated with a statin. The results of a trial of 4 g/d prescription EPA+DHA in hypertriglyceridemia are anticipated in 2020. We conclude that prescription n-3 FAs (EPA+DHA or EPA-only) at a dose of 4 g/d (>3 g/d total EPA+DHA) are an effective and safe option for reducing triglycerides as monotherapy or as an adjunct to other lipid-lowering agents.

Primary Aldosteronism: Cardiovascular Outcomes Pre- and Post-treatment.

Primary aldosteronism (PA) is a common form of hypertension characterized by autonomous aldosterone secretion from one or both adrenal glands. The purpose of this review is to synthesize recent research findings regarding cardiovascular disease risk in PA both pre- and post-targeted therapy. Previously considered a rare disease, recent prevalence studies demonstrate that PA is actually a very common, yet vastly under-diagnosed, etiology of hypertension. Prior to targeted therapy, PA is associated with substantially higher rates of cardiovascular disease compared with essential hypertension. Surgical adrenalectomy is highly effective in curing or improving hypertension as well as mitigating cardiovascular disease risk in patients with unilateral PA. For the remainder of PA patients, MR antagonists are recommended; however, several recent studies have brought into question their effectiveness in improving cardiovascular outcomes. PA is a common cause of hypertension that leads to disproportionately high rates of cardiovascular disease. Future studies are needed to enhance the clinical approach to both identification and treatment of patients with PA to optimize long-term cardiovascular outcomes.

AMPK-SIRT1-independent inhibition of ANGPTL3 gene expression is a potential lipid-lowering mechanism of metformin.

Hypertriglyceridaemia enhances cardiovascular disease risk in patients with diabetes. Lipoprotein lipase (LPL) regulates plasma triglyceride levels by hydrolysing chylomicrons and very-low-density lipoprotein (VLDL). Metformin, an antidiabetic drug, improves plasma lipids including triglycerides. We examined metformin's regulation of angiopoietin-like 3 (ANGPTL3), a liver-derived secretory protein with LPL inhibitory property. Using HepG2 cells, a human hepatocyte cell line, the effects of metformin on ANGPTL3 gene and protein expression were determined. The role of AMPK-SIRT1 pathway in metformin regulation of ANGPTL3 was determined using pharmacological, RNAi and reporter assays. Metformin regulation of ANGPTL3 expression was also examined in sodium palmitate-induced insulin resistance. Metformin and pharmacological activators of AMPK and SIRT1 inhibited the expression of ANGPTL3 in HepG2 cells. Pharmacological or RNAi-based antagonism of AMPK or SIRT1 failed to affect metformin inhibition of ANGPTL3. AMPK-SIRT1 activators and metformin exhibited distinct effects on the expression of ANGPTL3 gene luciferase reporter. Sodium palmitate-induced insulin resistance in cells resulted in increased ANGPTL3 gene expression which was suppressed by pretreatment with metformin. Metformin inhibits ANGPTL3 expression in the liver in an AMPK-SIRT1-independent manner as a potential mechanism to regulate LPL and lower plasma lipids.

Inflammation and Apparent Treatment-Resistant Hypertension in Patients With Chronic Kidney Disease.

Apparent treatment-resistant hypertension (ATRH) is highly prevalent and associated with cardiovascular disease risk in patients with chronic kidney disease. We analyzed the association of inflammatory biomarkers with ATRH and its complications in patients with chronic kidney disease. ATRH was defined as blood pressure ≥140/90 mm Hg while taking ≥3 antihypertensive medications or blood pressure <140/90 mm Hg while taking ≥4 medications. Analyses included 1359 CRIC study (Chronic Renal Insufficiency Cohort) participants with ATRH and 2008 hypertensive participants without. Logistic regression was used to examine cross-sectional associations of inflammatory biomarkers and ATRH adjusting for demographic, lifestyle, and clinical risk factors and treatments. Cox proportional hazards models were used to assess the impact of inflammatory biomarkers on associations of ATRH with composite cardiovascular disease and mortality beyond conventional risk factors. Multivariable-adjusted odds ratio (95% CI) of ATRH for the highest tertile versus the lowest tertile of inflammatory biomarker levels was 1.29 (95% CI, 1.05-1.59) for IL (interleukin)-6, 1.49 (95% CI, 1.20-1.85) for TNF-α (tumor necrosis factor-α), and 0.77 (95% CI, 0.63-0.95) for TGF-β (transforming growth factor-β). High-sensitivity CRP (C-reactive protein), fibrinogen, IL-1β, and IL-1 receptor antagonist were not significantly associated with ATRH. Adding inflammatory biomarkers to Cox models did not attenuate the significant association of ATRH with cardiovascular disease and mortality. Our findings show higher levels of IL-6 and TNF-α and lower levels of TGF-β were independently associated with odds of ATRH. Targeting specific inflammatory pathways may improve blood pressure control in patients with chronic kidney disease.

Apparent Treatment-Resistant Hypertension and Cardiovascular Risk in Hemodialysis Patients: Ten-Year Outcomes of the Q-Cohort Study

There has been limited data discussing the relationship between apparent treatment-resistant hypertension (ATRH) and cardiovascular disease risk in patients receiving maintenance hemodialysis. We analyzed data for 2999 hypertensive patients on maintenance hemodialysis. ATRH was defined as uncontrolled blood pressure despite the use of three or more classes of antihypertensive medications, or four or more classes of antihypertensive medications regardless of blood pressure level. We examined the relationships between ATRH and cardiovascular events using a Cox proportional hazards model. The proportion of participants with ATRH was 18.0% (539/2999). During follow-up (median: 106.6 months, interquartile range: 51.3–121.8 months), 931 patients experienced cardiovascular events including coronary heart disease (n = 424), hemorrhagic stroke (n = 158), ischemic stroke (n = 344), and peripheral arterial disease (n = 242). Compared with the non-ATRH group, the ATRH group showed a significant increased risk of developing cardiovascular disease (hazard ratio [HR]: 1.27; 95% confidence interval [CI]: 1.08–1.49), coronary heart disease (HR: 1.28; 95% CI: 1.01–1.62), ischemic stroke (HR: 1.31; 95% CI: 1.01–1.69), and peripheral arterial disease (HR: 1.42; 95% CI: 1.06–1.91) even after adjusting for potential confounders. This study demonstrated that ATRH was significantly associated with increased cardiovascular risk in hemodialysis patients.

Viscus fat area contributes to the Framingham 10-year general cardiovascular disease risk in patients with type 2 diabetes mellitus

ObjectiveTo explore the correlation of the viscus fat area (VFA) with the Framingham 10-year general cardiovascular disease risk in patients with type 2 diabetes mellitus (T2DM). MethodsA total of 202 patients with T2DM were divided into two groups based on VFA (a VFA ≥ 100 cm2 group and a VFA < 100 cm2 group), or four groups based on sex and age (a middle-aged male group, an elderly male group, a middle-aged female group, and an elderly female group). The correlation between the Framingham 10-year general cardiovascular disease risk and body fat indexes was analyzed. ResultsPatients in the VFA ≥ 100 cm2 group had higher body fat indexes and Framingham Risk Scores (FRSs) and lower levels of high density lipoprotein-cholesterol (HDL-C) when compared to the VFA < 100 cm2 group (P < 0.05). Female patients had higher body fat mass (BFM) and body fat percentage (BFP) levels and a lower VFA when compared to male patients. The VFA was significantly higher in the elderly than in the middle-aged patients. The waist hip fat ratio (WHFR) was significantly higher in elderly females than in elderly males (P < 0.05). Elderly females had the highest FRS of all patients. Multiple stepwise regression analysis revealed the VFA as a contributor to the Framingham 10-year general cardiovascular disease risk after statistical correction for other multiple factors affecting cardiovascular disease risk. ConclusionThe VFA is an independent factor that contributes to the Framingham 10-year general cardiovascular disease risk in patients with T2DM.