tbuckley/cabot-search huggingface dataset:
We Dropped the Reflex Hammer on Hypertension 20 Years Ago
Authors: Conrado J. Estol
Journal: JAMA Neurology (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
Slowing Progression of Cardiovascular Calcification With SNF472 in Patients on Hemodialysis
Authors: Paolo Raggi, Antonio Bellasi, David Bushinsky, Jordi Bover, Mariano Rodriguez, Markus Ketteler, Smeeta Sinha, Carolina Salcedo, Kristen Gillotti, Claire Padgett, Rekha Garg, Alex Gold, Joan Perelló, Glenn M. Chertow
Journal: Circulation (2019)

Background: The high cardiovascular morbidity and mortality in patients with end-stage kidney disease could be partially caused by extensive cardiovascular calcification. SNF472, intravenous myo-inositol hexaphosphate, selectively inhibits the formation and growth of hydroxyapatite. Methods: This double-blind, placebo-controlled phase 2b trial compared progression of coronary artery calcium volume score and other measurements of cardiovascular calcification by computed tomography scan during 52 weeks of treatment with SNF472 or placebo, in addition to standard therapy, in adult patients with end-stage kidney disease receiving hemodialysis. Patients were randomized 1:1:1 to SNF472 300 mg (n=92), SNF472 600 mg (n=91), or placebo (n=91) by infusion in the hemodialysis lines thrice weekly during hemodialysis sessions. The primary end point was change in log coronary artery calcium volume score from baseline to week 52. The primary efficacy analysis combined the SNF472 treatment groups and included all patients who received at least 1 dose of SNF472 or placebo and had an evaluable computed tomography scan after randomization. Results: The mean change in coronary artery calcium volume score was 11% (95% CI, 7–15) for the combined SNF472 dose group and 20% (95% CI, 14–26) for the placebo group ( P =0.016). SNF472 compared with placebo attenuated progression of calcium volume score in the aortic valve (14% [95% CI, 5–24] versus 98% [95% CI, 77–123]; P &lt;0.001) but not in the thoracic aorta (23% [95% CI, 16–30] versus 28% [95% CI, 19–38]; P =0.40). Death occurred in 7 patients (4%) who received SNF472 and 5 patients (6%) who received placebo. At least 1 treatment-emergent adverse event occurred in 86%, 92%, and 87% of patients treated with SNF472 300 mg, SNF472 600 mg, and placebo, respectively. Most adverse events were mild. Adverse events resulted in discontinuation of SNF472 300 mg, SNF472 600 mg, and placebo for 14%, 29%, and 20% of patients, respectively. Conclusions: Compared with placebo, SNF472 significantly attenuated the progression of coronary artery calcium and aortic valve calcification in patients with end-stage kidney disease receiving hemodialysis in addition to standard care. Future studies are needed to determine the effects of SNF472 on cardiovascular events. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02966028.
Selective Persulfide Detection Reveals Evolutionarily Conserved Antiaging Effects of S-Sulfhydration
Authors: Jasmina Zivanovic, Emilia Kouroussis, Joshua B. Kohl, Bikash Adhikari, Biljana Bursac, Sonia Schott-Roux, Dunja Petrovic, Jan Lj. Miljkovic, Daniel Thomas-Lopez, Youngeun Jung, Marko Miler, Sarah Mitchell, Verica Milosevic, Jose Eduardo Gomes, Moran Benhar, Bruno Gonzalez-Zorn, Ivana Ivanovic-Burmazovic, Roberta Torregrossa, James R. Mitchell, Matthew Whiteman, Guenter Schwarz, Solomon H. Snyder, Bindu D. Paul, Kate S. Carroll, Milos R. Filipovic
Journal: Cell Metabolism (2020)
Abstract 40: Empirical Comparison of Approaches to Mediation Analyses in Nutrition Research With Applications to the Quality Cohort
Authors: Karine Suissa, Andrea Benedetti, Melanie Henderson, Katherine Gray-Donald, Gilles Paradis
Journal: Circulation (2020)

Background: Adiposity may mediate the effect of dietary glycemic load (GL) on lipid profile in children as studies have shown an association between dietary GL and adiposity and between adiposity and lipid profiles. While several approaches for conducting mediation analysis have been proposed, given the strict assumptions and restrictions for each method, it is not clear which method is ideal in nutrition research. Our objective was to compare the conventional approach and the causal approach using marginal structural models (MSM) with inverse probability weights (IPW) to examine adiposity as a mediator in the association between baseline dietary GL and lipid profile after 2 years. Methods: The QUALITY cohort included 630 children, 8-10 years at recruitment with at least one obese parent followed-up 2 years later. Three separate 24-hour dietary recalls were administered by a dietitian at baseline. Child and parent characteristics were obtained through direct measurement (blood lipids, anthropometrics) or questionnaires (socio-economic characteristics). Indicators of adiposity, including BMI z-score and percent fat mass, were the mediators of interest. A conventional approach of statistical adjustment for the mediator was used. As well, we used MSM to estimate the controlled direct effect (CDE) between GL and blood lipids 2 years later not mediated by adiposity. The MSM models were constructed using IPW truncated at 5-95 percentile. Results: Mean age of children at baseline was 9.6 years and 33% were overweight or obese. Both mediation analysis methods revealed that most of the effect of GL on blood lipids was mediated by adiposity. Results obtained from both methods differed; while the MSM with IPW did not show evidence of a direct effect of GL on TG not via percent fat mass (TG: β=0.06, 95%CI=-0.01, 0.12; HDL: β=-0.01, 95%CI=-0.04, 0.03), the conventional method did (TG: β=0.03, 95%CI=0.003, 0.06; HDL: β=-0.02, 95%CI=-0.03, -0.001). Conclusion: In conclusion, our results suggest that adiposity contributes substantially to the association between GL and blood lipids after 2 years. MSM with IPW may not be appropriate in nutritional studies with small sample sizes.
Abstract P148: Sex Differences in the Genetic Predisposition of Coronary Artery Disease
Authors: Yunfeng Huang, Qin Hui, Marta Gwinn, Yijuan Hu, Arshed A Quyyumi, Viola Vaccarino, Yan Sun
Journal: Circulation (2020)

While coronary artery disease (CAD) is the leading cause of death for both men and women, sex differences in CAD risk are widely observed. Genetic susceptibility for CAD may be modified by sex and contribute to sex disparities in CAD. However, whether such modification exists is not clear given the limited sample size of previous studies. Using the UK Biobank, we constructed a CAD genetic risk score (CAD-GRS) based on 161 known loci, and assessed the sex-specific effect of the CAD-GRS on CAD incidence in ~307,147 men and women of European ancestry without previous history of CAD. During an average follow-up of 6.1 years 9,847 incident CAD events were identified using hospitalization data and the national death registry. To examine if certain intermediate trait contributes more predominantly on sex differences in CAD risk, we constructed three risk factor-based CAD-sub-GRSs after removing pleiotropic SNPs: 1) 26 loci associated with blood pressure (BP) and CAD (BP-sub-GRS); 2) 17 loci associated with lipids and CAD (lipids-sub-GRS); and 3) 16 loci associated with body mass index (BMI) and CAD (BMI-sub-GRS). Sex-specific effects of CAD-sub-GRSs were examined. Cox models were implemented to assess sex-specific genetic effects of CAD adjusted for age, smoking, alcohol drinking, history of hypertension and diabetes, BMI, cholesterol medication, education and SES, and population stratification. To avoid over-adjustment, history of hypertension, cholesterol medication and BMI were not controlled for in the analyses of BP-sub-GRS, lipids-sub-GRS and BMI-sub-GRS, respectively. Both CAD-GRS and CAD-sub-GRSs were categorized using quintiles into “low” (quintile 1), “intermediate” (quintile 2 - 4), and “high” (quintile 5) groups. We observed a strong sex discrepancy in the effect of the overall CAD-GRS on CAD incidence (HR high GRS vs. low GRS = 2.4 (95% CI: 2.2, 2.6) for males vs. HR high GRS vs. low GRS = 1.8 (95% CI: 1.6, 2.0) for females, interaction p-value = 0.002). A similar gene-sex interaction was observed for CAD-sub-GRS driven by BP-associated loci (HR high GRS vs. low GRS = 1.5 (95% CI: 1.4, 1.7) for males vs. HR high GRS vs. low GRS = 1.2 (95% CI: 1.1, 1.3) for females, interaction p-value = 0.0005) but not lipids or BMI-associated loci. The SNP-based analysis revealed significant gene-sex interaction (p=0.0001) at one CAD locus (21q22.11). The lead SNP (rs28451064) is a cis -eQTL for several neighboring genes’ expression ( MRPS6 , SLC5A3 , KCNE2 and AP000318.2 ) in aorta and tibial artery tissues. Previous genome-wide association studies reported significant associations between rs28451064 and bone mineral density, waist-hip ratio as well as pulse pressure. These results suggest that genetic predisposition of CAD based on known loci is stronger in men than in women. Future investigations of genetic risk and mechanism for CAD need to consider sex-specific effects.
Abstract P529: Altered Gut Microbiota in Obesity and Cardiometabolic Traits: Results From the Hispanic Community Health Study/Study of Latinos
Authors: Zheng Wang, Tao Wang, Mykhaylo Usyk, Yoshiki Vazquez-Baeza, Carmen R Isasi, Jessica S Williams-nguyen, Simin Hua, Daniel McDonald, Bharat Thyagarajan, Martha L DAVIGLUS, Jianwen Cai, Kari E North, Rob Knight, Robert Burk, Qibin Qi, Robert Kaplan
Journal: Circulation (2020)

Introduction: The relationship between gut microbiome and human obesity is not fully elucidated. Most evidence is from animal models or small case-control studies. Data in population-based cohort are limited. Hypothesis: We hypothesized that some specific bacterial taxonomy are associated with host obesity, some of them may also associated with obesity-related cardiometabolic traits. Methods: This study included 2759 participants from the HCHS/SOL. Fecal samples were analyzed by shotgun metagenomics sequencing, with the SHOGUN pipeline for bacterial taxonomic identification. Multivariate linear regression models were used to examine associations of bacterial genera with multiple obesity and cardiometabolic traits. Results: Of 87 predominant genera (average relative abundance &gt;0.01%), 43 were significantly associated with BMI after multiple testing correction ( Fig 1 ). These included some known obesity-associated taxa (e.g., Acidaminococcus , Dorea etc.) , some taxa with controversial results in human and animal studies (e.g, Methanobrevibacter ), and some novel links with obesity (e.g, Cloacibacillus) . Among these 43 BMI-associated genera, 18 were associated with waist-to-hip ratio (WHR), and 15 were associated with body fat percentage (BF%) but not with fat free mass (FFM). Several obesity-related genera were associated with multiple cardiometabolic traits. For instance, Dorea , a glutamate metabolism related genus, was associated with higher levels of BMI, WHR, BF%, dystopic blood pressure, fasting glucose, fasting insulin and HOMA-IR. Cloacibacillus showed inverse associations with BMI, BF%, triglyceride, fasting insulin and HOMA-IR, and positive association with HDL. Methanobrevibacter , a methane producer which related to human energy harvest , was associated with lower levels of BMI, BF%, triglyceride and HOMA-IR(all p &lt;0.05). Conclusion: This study in a large US Hispanic/Latino cohort identified multiple gut microbial genera associated with human obesity and related cardiometabolic traits.
Abstract MP30: The Health and Economic Impact of a Sugar Sweetened Beverage Tax in New York City: A Modeling Study
Authors: Daniel D Bu, Stella S Yi, Heesun Eom, Rienna Russo, Brandon Bellows, Yiyi Zhang, Claire Wang, David S Siscovick, Jose Pagan, Andrew E Moran, Yan Li
Journal: Circulation (2020)

Background: Sugar-sweetened beverages (SSB) are currently the single largest source of added sugar in the US diet, and consumption in New York City (NYC) remains high. Evidence suggests that a high sugar consumption increases the risk of coronary heart disease. To date, excise taxes on SSB have been implemented in several US jurisdictions. While reductions in SSB consumption have been reported in several places where the SSB tax was implemented, it is unclear what the long term health and economic impact an SSB tax could have within the demographically and socioeconomically diverse NYC. In addition, the impact of varying tax structures remains unknown. Objective: To project the cardiovascular health outcomes and cost-savings of variations on the penny-per-ounce SSB tax structure (simulating a half-penny to two-penny range) using a validated microsimulation model of cardiovascular disease. Methods: The Simulations for Health Improvement and Equity (SHINE) CVD Model was used to estimate the lifetime direct medical costs (2019 USD) and effectiveness of SSB tax from a healthcare sector perspective. Population demographics and health profiles were estimated using data from the 2013-2014 NYC Health and Nutrition Examination Survey. CVD risk factor trajectories and risk of incident CVD events were derived from six pooled prospective U.S. cohorts. Policy effects and price elasticity were derived from recent meta-analyses. SSB tax was modeled to directly affect incidence rates of CVD events and was derived from variations of the penny-per-ounce tax scheme. Costs were discounted at 3%. Results: Compared to the non-policy situation, the SHINE CVD model projected that an SSB tax would prevent 29,341 (95% CI: 11,747-46,935) coronary heart disease (CHD) events at a half penny-per-ounce rate, 37,034 (95% CI: 19,336-54,732), at one penny-per-ounce, and 68,846 CHD events (95% CI: 51,306- 86,386) at a two-pennies-per-ounce rate over the simulated lifetimes of the NYC population. Total cost savings over this time period ranged from $662 million (95% CI $584-$741 million), $714 million (95% CI: $620-$808 million), and $1.03 billion (95% CI $0.92 - $1.16 billion), or $13.5 million/year, $14.6 million/year, $21.0 million/year for half-penny, one-penny, and two-pennies-per-ounce taxes respectively. Conclusion: Using a computer simulation model, we showed how different increments of the penny-per-ounce SSB tax could result in substantial benefits within the NYC population in terms of CVD outcomes and overall health care cost savings. Results from the SHINE CVD model may inform the ongoing policymaking efforts.
Improving Racial and Ethnic Minority Representation in Cardiovascular Disease Trials to Advance Health Equity—Reply
Authors: Robert T. Sparrow, Laura E. Ferreira-Legere, Jacob A. Udell
Journal: JAMA Cardiology (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
Abstract P545: Insufficient Sleep and Nitric Oxide-Mediated Endothelium-Dependent Vasodilation in Adults With Elevated Blood Pressure
Authors: Kelly A Stockelman, Anthony R Bain, Dana M Withrow, Tracey A Larson, Elizabeth M Boland, Jared J Greiner, John R Harsh, Brian L Stauffer, Kenneth P Wright, Christopher A Desouza
Journal: Circulation (2020)

Elevated blood pressure (BP ≥130/80 mmHg) is associated with increased risk for myocardial infarction, heart failure, stroke and vascular disease. Insufficient nightly sleep (&lt;7 h/night) has been linked not only to the etiology of elevated blood pressure but is a prevalent, often ignored, comorbidity. Indeed, short sleep duration is now considered to be a plausible risk factor for elevated blood pressure and a harbinger of increased cardiovascular risk. A high prevalence of insufficient nightly sleep has been reported in adults with elevated blood pressure. The influence of insufficient sleep on endothelial vasodilator function in adults with elevated blood pressure is unknown. We tested the hypotheses that chronic insufficient sleep is associated with diminished nitric oxide (NO)-mediated endothelium-dependent vasodilation in adults with elevated blood pressure. Moreover, the insufficient sleep-related reduction in endothelial vasodilator function is due, at least in part to increased oxidative stress. Thirty-five middle-aged and older adults with elevated blood pressure were studied: 15 with normal nightly sleep duration (11M/4F; age: 58±2 yr; BP: 136/82±1/2 mmHg; sleep: 7.6±0.2 h/night) and 20 with short nightly sleep duration (14M/6F; 58±1 yr; BP: 138/84±1/1 mmHg; sleep: 6.0±0.1 h/night). Forearm blood flow (FBF) responses to intra-arterial infusion of acetylcholine (ACh), in the absence and presence of the endothelial NO synthase inhibitor N G -monomethyl-L-arginine (L-NMMA) and the antioxidant vitamin C were determined by venous occlusion plethysmography. The FBF response to ACh was significantly lower (~20%) in the short sleep (from 3.8±0.2 to 11.0±0.6 ml/100 ml tissue/min) compared with the normal sleep duration group (from 4.2±0.2 to 13.6±0.6 ml/100 ml tissue/min). L-NMMA significantly reduced (~25%) the FBF response to ACh in the normal sleep but not the short sleep group. Vitamin C markedly increased (~35%; P&lt;0.05) the vasodilator response to ACh in short sleepers only. In summary, habitual short sleep duration worsens NO-mediated endothelium-dependent vasodilation in adults with elevated blood pressure. Furthermore, the sleep-related diminishment in endothelial vasodilator function is due, in part, to increased oxidative stress.
Colorectal cancer statistics, 2020
Authors: Rebecca L. Siegel, Kimberly D. Miller, Ann Goding Sauer, Stacey A. Fedewa, Lynn F. Butterly, Joseph C. Anderson, Andrea Cercek, Robert A. Smith, Ahmedin Jemal
Journal: CA A Cancer Journal for Clinicians (2020)

Colorectal cancer (CRC) is the second most common cause of cancer death in the United States. Every 3 years, the American Cancer Society provides an update of CRC occurrence based on incidence data (available through 2016) from population-based cancer registries and mortality data (through 2017) from the National Center for Health Statistics. In 2020, approximately 147,950 individuals will be diagnosed with CRC and 53,200 will die from the disease, including 17,930 cases and 3,640 deaths in individuals aged younger than 50 years. The incidence rate during 2012 through 2016 ranged from 30 (per 100,000 persons) in Asian/Pacific Islanders to 45.7 in blacks and 89 in Alaska Natives. Rapid declines in incidence among screening-aged individuals during the 2000s continued during 2011 through 2016 in those aged 65 years and older (by 3.3% annually) but reversed in those aged 50 to 64 years, among whom rates increased by 1% annually. Among individuals aged younger than 50 years, the incidence rate increased by approximately 2% annually for tumors in the proximal and distal colon, as well as the rectum, driven by trends in non-Hispanic whites. CRC death rates during 2008 through 2017 declined by 3% annually in individuals aged 65 years and older and by 0.6% annually in individuals aged 50 to 64 years while increasing by 1.3% annually in those aged younger than 50 years. Mortality declines among individuals aged 50 years and older were steepest among blacks, who also had the only decreasing trend among those aged younger than 50 years, and excluded American Indians/Alaska Natives, among whom rates remained stable. Progress against CRC can be accelerated by increasing access to guideline-recommended screening and high-quality treatment, particularly among Alaska Natives, and elucidating causes for rising incidence in young and middle-aged adults.
Abstract P179: Uncontrolled Cholesterol Levels In Patients With Severe Hypercholesterolemia
Authors: Nicole Groth, Catherine P Benziger
Journal: Circulation (2020)

Introduction: The 2018 American Heart Association/American College of Cardiology cholesterol guidelines recommends patients who have phenotypic severe hypercholesterolemia (SH), defined as a low-density lipoprotein-cholesterol (LDL-c) &gt; 190 mg/dL, be started on maximally tolerated statin therapy without further risk stratification due to high risk for cardiovascular disease (CVD). SH patients on guideline-directed medical therapy (GDMT) should have 50% reduction in their LDL-c levels, with optimal being &lt; 100 mg/dL for primary prevention and &lt;70 mg/dL for secondary prevention. The 2019 European Society of Cardiology/European Atherosclerosis Society cholesterol guidelines recommend an optimal LDL-c level &lt; 55 mg/dL. Hypothesis: LDL-c levels vary by intensity of medication and are not at target in patients with SH in a large rural healthcare system. Methods: We used an electronic medical record-based SH registry defined by ever having an LDL-c &gt; 190 mg/dL since 01/01/2000 (n=17,925) at Essentia Health (MN, WI, and ND). In this cross-sectional study, patients were excluded if they had: no recent visit within the past 5 years (n=209), &lt;20 or &gt;75 years (n=3,153), listed as being on a statin but intensity was unavailable (n=1,934), or had no recent lab (n=998). Methods: We included 12,283 patients (68.5%)(mean age 59.4 + 10.1 years; 59.5% female) with SH and of these only 22.9% were on a high-intensity statin or proprotein convertase subtilisin/kexin type 9 inhibitor. Of the patients that were not on any lipid-lowering therapy (n=4,971; 40.5%), only 16.8% (n=837) had a statin allergy or intolerance documented. Figure 1 shows the most recent LDL-c levels; &lt;10% of patients in each group had a most-recent LDL-c &lt;70 mg/dL, and 9.4% had an LDL-c &lt;55mg/dL. Conclusions: Most SH patients remain untreated or undertreated with GDMT with recent LDL-c levels above target. More aggressive lipid-lowering therapy in patients with SH is needed to reduce risk of CVD.