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Background: Cardiovascular disease (CVD) is associated with high mortality in the United States, but the burden of CVD mortality is unevenly distributed between demographic and geographic subgroups, with poor characterization of state-specific trends. In this study, the disparities in CVD-related mortality trends in Texas and the United States from 1999 to 2019 were assessed., Methods: Trends in CVD-related mortality were evaluated through analysis of the Multiple Causes of Death Files from the National Center for Health Statistics. Crude and age-adjusted mortality rates (AAMRs) per 100,000 population with associated annual percentage changes were determined. Joinpoint regression was used to assess trends in the CVD-related mortality rates., Results: Between 1999 and 2019, 29,455,193 CVD-related deaths were reported in the United States, of which 1,937,166 occurred in Texas. After an initial decline in the overall AAMR in Texas (annual percentage change, -2.5 [95% CI, -2.8 to -2.1]), a steady level was maintained from 2009 to 2019 (annual percentage change, 0.2 [95% CI, -0.5 to 0.2]). In the United States, after initial decline, AAMR plateaued from 2011 to 2019. Overall, CVD-related AAMR was slightly higher in Texas than in the overall United States (AAMR, 674.1 [95% CI, 673.2-675.1] vs 654 [95% CI, 653.8-654.3]). Men, non-Hispanic Black people, and people 85 years of age and older had the highest AAMRs in Texas and nationwide. Nonmetropolitan areas, both nationally and in Texas, consistently had higher mortality rates. The AAMRs also varied significantly by county within Texas., Conclusion: Despite an initial period of decline, CVD-related mortality rates have plateaued in Texas and the United States. Higher AAMRs were observed in Texas than in the overall United States. Prevalent disparities also exist based on demographic and geographic subgroups., Competing Interests: Conflict of Interest Disclosure: None., (© 2024 The Authors. Published by The Texas Heart Institute®.)

Introduction: The absence of coronary artery calcium (CAC = 0) is associated with low risk of stroke events; however, predictors of incident stroke among those with CAC = 0 are not known., Methods: Individual participant-level data were pooled from three prospective cohorts (Multi-Ethnic Study of Atherosclerosis [MESA], Jackson Heart Study, and Framingham Heart Study). Multivariable-adjusted Cox proportional hazards models were used to study the association between cardiovascular risk factors and incident adjudicated stroke among individuals with CAC = 0 who were free of clinical atherosclerotic cardiovascular disease at baseline., Results: Among 6180 participants (mean age 53 [SD 11] years, 62% women, and 44% White, 36% Black, and 20% other individuals), over a median (IQR) follow up of 15 (12-16) years, there were 122 strokes (95 ischemic, 27 hemorrhagic) with an overall unadjusted event rate of 2.0 per 1000 person-years. After multivariable adjustment, risk factors associated with overall stroke included (hazard ratio [95% CI]) systolic blood pressure (SBP): 1.19 (1.05-1.36) per 10-mmHg increase and carotid intima-media thickness (CIMT): 1.21 (1.04-1.42) per 0.1-mm increment. Current cigarette smoking: 2.68 (1.11-6.50), SBP: 1.23 (1.06-1.42) per 10-mmHg increase, and CIMT: 1.25 (1.04-1.49) per 0.1-mm increment were associated with ischemic stroke, whereas C-reactive protein was associated with hemorrhagic stroke risk (0.49, 0.25-0.93)., Conclusion: In a large cohort of individuals with CAC = 0, the rate for incident stroke was low (2.0 per 1000-person years) and was associated with modifiable risk factors., Competing Interests: Declaration of conflicting interestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Vijay Nambi: site PI study sponsored by Merck and Amgen. Christie M Ballantyne: received grant/research support (to his institution) from Abbott Diagnostic, Akcea, Amgen, Arrowhead, Esperion, Ionis, Merck, Novartis, Novo Nordisk, Regeneron, and Roche Diagnostic; and has been a consultant for 89bio, Abbott Diagnostics, Alnylam Pharmaceuticals, Althera, Amarin, Amgen, Arrowhead, AstraZeneca, Denka Seiken, Esperion, Genentech, Gilead, Illumina, Matinas BioPharma Inc., Merck, New Amsterdam, Novartis, Novo Nordisk, Pfizer, Regeneron, and Roche Diagnostic. Salim S Virani: received research funding from Department of Veterans Affairs, NIH, World Heart Federation, and Tahir and Jooma Family; and receives honorarium from the American College of Cardiology. The remaining authors have no conflicts of interest.

Background: The burden of atrial fibrillation (AF) hospitalizations in young patients is not well characterized. We aimed to study the burden, comorbidities, outcomes, and resource utilization of AF hospitalizations in young patients., Methods: We conducted a retrospective analysis of all primary AF hospitalizations in patients 18-45 years of age using the National Inpatient Sample data from January 1, 2008 to December 31, 2019. We collected data on various clinical and socioeconomic features including demographics and clinical outcomes., Results: AF hospitalizations decreased over time from 18.7 per 100,000 in 2008 to 13.0 per 100,000 in 2019 (p < 0.001). AF hospitalizations were higher amongst males compared to females (24.0 vs. 7.5 per 100,000), and higher in Black patients compared to other ethnicities (20.4 for Black vs. 15.6 for White vs. 8.5 Hispanic per 100,000). The utilization of electrical cardioversion increased from 17.6% in 2008 to 21.9% in 2019 (p < 0.001), and catheter ablation decreased from 7.1% in 2008 to 4.3% in 2019 (p < 0.001). Men were more likely to undergo electrical cardioversion than women (20.1% vs. 14.8%, p < 0.001). White patients were more likely to undergo electrical cardioversion (20.8% vs. 14.3% vs. 15.5%, p < 0.001) and catheter ablation (6.1% vs. 3.3% vs. 4.2%, p < 0.001) compared to Black and Hispanic patients, respectively. Patients in the highest income residence quartile were more likely to undergo electrical cardioversion (21.9% vs. 16.4%, p < 0.001) and catheter ablation (8.0% vs. 3.7%, p < 0.001) compared to patients in the lowest income residence quartile., Conclusions: We found significant differences in inpatient AF management based on sex, ethnicity, and SES., (© 2024 Wiley Periodicals LLC.)

Background: Geographic physician availability differences are associated with healthcare outcomes. However, the association between primary care physician (PCP) density and mortality outcomes is less well-established., Methods: The study analyzed 2019 county-level nonfederal PCP data from the Health Resources and Services Administration Area Health Resource File and mortality data using the CDC WONDER (Wide-ranging Online Data for Epidemiologic Research). All-cause and cardiovascular disease (CVD)- related age-adjusted mortality rates (AAMR) per 100,000 population stratified by the number of PCPs per 100,000 quartiles were extracted. Using AAMRs as continuous variables, linear regression was performed to determine the association of AAMRs with PCPs per 100,000 (reference, first quartile), adjusting for the social vulnerability index (SVI)., Results: A total of 3142 counties were included in the analysis. Among counties stratified by PCPs per 100,000 quartiles, all-cause AAMRs were 828 (95% CI, 824-832) in the first quartile, 798 (95% CI, 796-801) in the second quartile, 737 (95% CI, 735-739) in the third quartile, and 679 (95% CI, 678-680) in the fourth quartile. Similar trends were seen in CVD-related AAMRs, which were 446 (95% CI, 443-449), 439 (95% CI, 437-441), 403 (95% CI, 402-404), and 365 (95% CI, 364-366), respectively. Counties without PCP (221, included in first quartile) had all-cause and CVD-related AAMR of 797 (95%CI, 783-812) and 430 (95%CI, 419-440), respectively. Compared with the first quartile, SVI-adjusted analyses showed β-coefficient (95%CI) of all-cause mortality for the second, third, and fourth quartiles of -4.11 (95% CI, -18.31, 10.08), -35.37 (95% CI, -49.57, -21.17) and -85.79 (95% CI, -100.10, -71.48). Similar results were observed for CVD-related AAMR., Conclusion: Higher PCP per 100,000 is generally associated with better all-cause and CVD-associated mortality outcomes, however complex factors likely play a role in determining these outcomes in counties with lower PCP per 100,000, which warrant further investigation., Competing Interests: Declaration of COMPETING Interest This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors., (Copyright © 2024 National Medical Association. Published by Elsevier Inc. All rights reserved.)

Aim: To study the prevalence of cardiovascular disease (CVD) and associated risk factors among different races/ethnicities across different income groups., Methods: This retrospective analysis included data from the National Health and Nutrition Examination Survey from 2005-2018. Adults >20 years who identified as non-Hispanic (NH) White, NH Black, or Hispanic were included. Family income-to-poverty ratio (PIR) was calculated by dividing family income by poverty guidelines specific to the survey year and divided into four quartiles. Weighted logistic regression was performed to estimate adjusted odds ratios to determine association of race/ethnicity and CVD in each PIR quartile. Models were adjusted for age, sex, race, health insurance, marital status, citizenship status, education level, and PIR., Results: We included 31,884 adults that corresponded to ∼191.3 million weighted, nationally representative participants. Of these, 8,009, 7,967, 7,944, and 7,964 participants belonged to 1 st , 2 nd , 3 rd , and 4 th quartiles, respectively. The prevalence of diabetes mellitus (DM), hypertension, coronary artery disease (CAD), congestive heart failure (CHF), and stroke decreased with each successive PIR quartile. NH Black participants had higher prevalence odds of DM, hypertension, obesity, CHF, and stroke compared to NH White participants. The difference in prevalence odds between NH White adults and NH Black adults was greater for obesity (p-interaction=0.002), DM (p-interaction=0.027), and stroke (p-interaction=0.053) in the 4 th PIR quartile (highest income) compared to the 1 st PIR quartile (lowest income)., Conclusion: Racial and ethnic disparities in the risk of CVD persists across income levels, with a greater difference in prevalence of select CVD and risk factors between NH Black and NH White participants in the highest income quartile compared to the lowest income quartile., (Copyright © 2024. Published by Elsevier Inc.)

Competing Interests: Disclosures: Disclosures are available with the article online.

Introduction: Research has shown chronic diseases can be associated with suicide but there is limited data on suicide in cardiovascular disease (CVD). Given the substantial psychosocial, financial, quality of life, and health impact of CVD, we aimed to study suicide-related mortality in CVD., Methods: We used Center for Disease Control Wide-ranging Online Data for Epidemiologic Research (CDC WONDER) to access Multiple Cause of Death data from 1999 to 2019. Suicide and CVD related deaths in patients ≥ 25 years were identified. Proportionate suicide-related mortality (PSrM) was calculated as suicide-related deaths (listed with CVD) divided by all CVD-related deaths (irrespective of suicide) and reported as PSrM per 100,000 CVD-related deaths. Joinpoint regression was used to examine trend changes using annual percentage change (APC) overall and by sex, race/ethnicity, disease subtype, and age., Results: Overall, PSrM in CVD increased from 62.8 in 1999 to 90.5 in 2019. The PSrM increased from 1999 to 2002 with an associated APC of 6.2 (95 % CI, 0.0 to 12.7), remained stable from 2002 to 2005, increased from 2005 to 2013 with an APC of 4.8 (95 % CI, 3.4 to 6.3), and decreased from 2013 to 2019 with an APC of -2.1 (95 % CI, -3.6 to -0.5). Among racial/ethnic groups, PSrM was highest in non-hispanic (NH) White (103.8), then Hispanic or Latino (63.6), and then NH Black or African American individuals (29.2). PSrM was highest in the 25-39 years age group (858), then 40-54 years (382.8), 55-69 years (146.2), 70-84 years (55.9), and then 85+ (17). PSrM initially increased in men with APC (3.1 until 2013), women (4.1 until 2014), NH White individuals (3.9 until 2013), Hispanic or Latino (3.5 until 2014), ages 40-54 years (2.9 until 2013), 55-69 years (6.0 until 2013), then stabilized or decreased. AAMR increased in NH Black or AA individuals APC (1.0) and 25-39 years APC (1.4) from 1999 to 2019., Conclusion: PSrM in CVD peaked in the early 2010s, with varying differences across sex, racial/ethnic, and age groups. Further research is needed to understand disparities and develop preventive strategies., (Copyright © 2024 National Medical Association. Published by Elsevier Inc. All rights reserved.)

Background: The impact of socioeconomic status on the clinical outcomes of patients admitted to the hospital for atrial fibrillation (AF) is not well described., Objective: The purpose of this study was to determine the association between median neighborhood household income (mNHI) and clinical outcomes among patients admitted to the hospital for AF., Methods: We retrospectively analyzed primary AF hospitalizations from the United States National Inpatient Sample between 2016 and 2020. The analyzed sample was divided into quartiles based on the mNHI in the zip code of the patient's residence. The lowest quartile was used as the reference category. Study outcomes included inpatient procedure utilization (ablation, cardioversion, percutaneous left atrial appendage closure), length of stay, cost, mortality, and disposition. Weighted multivariable logistic and linear regression, adjusting for multiple patient and hospital-level characteristics, was performed., Results: Patients in the highest mNHI quartile had lower comorbidity burden, lower in-hospital mortality (odds ratio [OR] 0.78; 95% confidence interval [CI] 0.7-0.87; P <.001), lower discharges to care facility (OR 0.86; 95% CI 0.83-0.9; P <.001), shorter length of stay (adjusted mean difference -0.26; 95% CI -0.30 to -0.22; P <.001), higher procedure utilization, and higher health care costs ($12,124 vs $10,018) compared to the lowest mNHI quartile patients., Conclusion: We identified significantly higher in-hospital mortality and lower procedural/resource utilization in patients living in lower-income neighborhoods compared to higher-income neighborhoods. Further research is needed to better understand the drivers of these disparities and the strategies to improve health care disparities between socioeconomic groups., Competing Interests: Disclosures The authors have no conflicts to disclose., (Copyright © 2024 Heart Rhythm Society. All rights reserved.)

Background: There are several studies that have analyzed disparities in cardiovascular disease (CVD) health using a variety of different administrative databases; however, a unified analysis of major databases does not exist. In this analysis of multiple publicly available datasets, we sought to examine racial and ethnic disparities in different aspects of CVD, CVD-related risk factors, CVD-related morbidity and mortality, and CVD trainee representation in the US., Methods: We used National Health and Nutrition Examination Survey, National Ambulatory Medical Care Survey, National Inpatient Sample, Centers for Disease Control and Prevention Wide-Ranging OnLine Data for Epidemiologic Research, United Network for Organ Sharing, and American Commission for Graduate Medical Education data to evaluate CVD-related disparities among Non-Hispanic (NH) White, NH Black and Hispanic populations., Results: The prevalence of most CVDs and associated risk factors was higher in NH Black adults compared to NH White adults, except for dyslipidemia and ischemic heart disease (IHD). Statins were underutilized in IHD in NH Black and Hispanic patients. Hospitalizations for HF and stroke were higher among Black patients compared to White patients. All-cause, CVD, heart failure, acute myocardial infarction, IHD, diabetes mellitus, hypertension and cerebrovascular disease related mortality was highest in NH Black or African American individuals. The number of NH Black and Hispanic trainees in adult general CVD fellowship programs was disproportionately lower than NH White trainees., Conclusion: Racial disparities are pervasive across the spectrum of CVDs with NH Black adults at a significant disadvantage compared to NH White adults for most CVDs., (Copyright © 2024 National Medical Association. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Conflict of interest: None declared.

Purpose: The association of social vulnerability and cardiovascular disease-related mortality in older adults has not been well characterized., Methods: The Centers for Disease Control and Prevention database was evaluated to examine the relationship between county-level Social Vulnerability Index (SVI) and age-adjusted cardiovascular disease-related mortality rates (AAMRs) in adults aged 65 and above in the United States between 2016 and 2020., Results: A total of 3139 counties in the United States were analyzed. Cardiovascular disease-related AAMRs increased in a stepwise manner from first (least vulnerable) to fourth SVI quartiles; (AAMR of 2423, 95% CI [confidence interval] 2417-2428; 2433, 95% CI 2429-2437; 2516, 95% CI 2513-2520; 2660, 95% CI 2657-2664). Similar trends among AAMRs were noted based on sex, all race and ethnicity categories, and among urban and rural regions. Higher AAMR ratios between the highest and lowest SVI quartiles, implying greater relative associations of SVI on mortality rates, were seen among Hispanic individuals (1.52, 95% CI 1.49-1.55), Non-Hispanic-Asian and Pacific Islander individuals (1.32, 95% CI 1.29-1.52), Non-Hispanic- American Indian or Alaskan Native individuals (1.43, 95% CI 1.37-1.50), and rural counties (1.21, 95% CI 1.20-1.21)., Conclusion: Social vulnerability as measures by the SVI was associated with cardiovascular disease-related mortality in older adults, with the association being particularly prominent in ethnic minority patients and rural counties., (Copyright © 2023 Elsevier Inc. All rights reserved.)

National estimates of deaths related to both heart failure (HF) and sleep apnea (SA) are not known. We evaluated the trends in HF and SA related mortality using the CDC-WONDER database in adults aged ≥25 years in the US. All deaths related to HF and SA as contributing or underlying causes of death were queried. Between 1999 and 2019, there were a total of 6,484,486 deaths related to HF, 204,824 deaths related to SA, and 53,957 deaths related to both. There was a statistically significant increase in the age-adjusted mortality rate (AAMR) for both SA-related (average annual percent change [AAPC] 8.2%) and combined HF and SA- related (AAPC 10.1 %) deaths. Men had consistently higher AAMRs compared with women, and both groups had a similar increasing trend in AAMR. Non-Hispanic (NH) Black individuals had the highest HF and SA-related AAMR, followed by NH White and Hispanic/Latino individuals. Adults aged >75 years consistently had the highest AAMR with the steepest increase (AAPC 11.1%). In conclusion, HF and SA-related mortality has significantly risen over the past two decades with the elderly, men, and NH Black at disproportionately higher risk., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Introduction: The 2017 American College of Cardiology/American Heart Association blood pressure guideline redefined hypertension and lowered the blood pressure treatment target. Empirical data on the guideline's impact are needed., Methods: Data were analyzed from Atherosclerosis Risk in Communities study participants who attended baseline pre-guideline (2016-2017) and post-guideline (2018-2019) visits with baseline systolic blood pressure between 120 and 159 mmHg. Participants were grouped according to baseline systolic blood pressure by change in classification under the new guideline as follows: not reclassified (120-129 mmHg), reclassified to Stage 1 hypertension (130-139 mmHg), and reclassified to Stage 2 hypertension (140-159 mmHg). Means and 95% CIs for systolic blood pressure changes between baseline and follow-up, changes in antihypertensive use, and percentages that achieved the post-guideline recommendation (systolic blood pressure <130 mmHg) were calculated. Analyses were performed in 2021-2022., Results: Among 2,193 community-dwelling Atherosclerosis Risk in Communities participants aged 71-95 years at baseline, systolic blood pressure changes between baseline and follow-up visits differed among participants not reclassified (+4.1 mmHg, 95% CI=3.0, 5.3 mmHg), reclassified to Stage 1 hypertension (-1.1 mmHg, 95% CI= -2.2, 0.1 mmHg), and reclassified to Stage 2 hypertension (-5.7 mmHg, 95% CI= -6.8, -4.7 mmHg). Antihypertensive use changed from 77.3% to 78.4% (p=0.25) among participants reclassified to Stage 1 hypertension and from 78.3% to 81.4% (p<0.01) among participants reclassified to Stage 2 hypertension. At follow-up, 41.8% of the Stage 1 and 22.4% of the Stage 2 hypertension groups reached the systolic blood pressure <130 mmHg goal., Conclusions: There were small decreases in systolic blood pressure and increases in antihypertensive therapy among older adults reclassified to Stage 2 hypertension but not among those reclassified to Stage 1 hypertension by the 2017 American College of Cardiology/American Heart Association guideline., (Copyright © 2023 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Introduction: The United States Preventive Services Taskforce (USPSTF) recently released recommendations for statin therapy eligibility for the primary prevention of cardiovascular disease (CVD). We report the proportion and the absolute number of US adults who would be eligible for statin therapy under these recommendations and compare them with the previously published 2018 American Heart Association (AHA)/ American College of Cardiology (ACC)/ Multisociety (MS) Cholesterol guidelines., Methods: We used data from the National Health and Nutrition Examination Survey (NHANES) 2017-2020 of adults aged 40-75 years without prevalent self-reported atherosclerotic CVD (ASCVD) and low-density lipoprotein-cholesterol <190 mg/dL. The 2022 USPSTF recommends statin therapy for primary prevention in those with a 10-year ASCVD risk of ≥10% and ≥ 1 CVD risk factor (diabetes mellitus, dyslipidemia, hypertension, or smoking). The 2018 AHA/ ACC/ MS Cholesterol guideline recommends considering statin therapy for primary prevention for those with diabetes mellitus, or 10-year ASCVD risk ≥20% or 10-year ASCVD risk 7.5 to <20% after accounting for risk-enhancers and shared decision making. Survey recommended weights were used to project these proportions to national estimates., Results: Among 1799 participants eligible for this study, the weighted mean age was 56.0 ± 0.5 years, with 53.0% women (95% confidence interval [CI] 49.7, 56.3), and 10.6% self-reported NH Black individuals (95% CI 7.7, 14.3). The weighted mean 10-year ASCVD risk was 9.6 ± 0.3%. The 2022 USPSTF recommendations and the 2018 AHA/ ACC/ MS Cholesterol guidelines indicated eligibility for statin therapy in 31.8% (95% CI 28.6, 35.1) and 46.8% (95% CI 43.0, 50.5) adults, respectively. These represent 33.7 million (95% CI 30.4, 37.2) and 49.7 million (95% CI 45.7, 53.7) adults, respectively. For those with diabetes mellitus, 2022 USPSTF recommended statin therapy in 63.0% (95% CI 52.1, 72.7) adults as compared with all adults with diabetes aged 40-75 years under the 2018 AHA/ ACC/ MS Cholesterol guidelines., Conclusion: In this analysis of the nationally representative US population from 2017 to 2020, approximately 15% (~16.0 million) fewer adults were eligible for statin therapy for primary prevention under the 2022 USPSTF recommendations as compared to the 2018 AHA/ ACC/ MS Cholesterol guideline., Competing Interests: Declaration of Competing Interest VB: Through contracts between UAB and the sponsor, VB was national coordinator for the STRENGTH Trial (Astra Zeneca) and the Dalgene trial (DalCor); is national coordinator for the CLEAR Outcomes trial (Esperion) and Steering Committee member for the ODYSSEY OUTCOMES trial (Sanofi/Regeneron) and serves as site PI for the ORION trial (Novartis). She was a consultant for Pfizer and currently serves on a Data Safety and Monitoring Board for Verve Therapeutics. LS: consulting honoraria from Amgen and Regeneron. NJS: honorarium for an educational presentation from Knowledge to Practice. This company has no ties to industry. CJL: Consultant and Speaker for Amgen and Sanofi on their PCSK9Is and for Novartis on their new injectable and speaker and consultant for DSM and GOED on omega-3, speaker and Consultant for Esperion., (Published by Elsevier Inc.)

Septic shock is a life-threatening host response to infection and a significant contributor to cost burden in the United States. Furthermore, sepsis-related inflammation has been linked to myocardial infarction (MI). We sought to examine the association of type 1 and type 2 MI with outcomes in hospitalizations admitted with septic shock. The National Readmission Database 2018 was queried to identify hospitalizations with hospital discharge diagnoses of septic shock without MI, septic shock with type 1 MI, or septic shock with type 2 MI. Complex-sample multivariable logistic and linear regression models were used to determine the association of these conditions with clinical outcomes. Of 354,528 hospitalizations with septic shock, 11,519 had type 1 MI (3.2%) and 13,970 had type 2 MI (3.9%). Compared with septic shock without MI, type 1 MI was associated with higher mortality (adjusted odds ratio [OR] 1.67, 95% confidence interval [CI] 1.57 to 1.77), costs (adjusted parameter estimate $4,571, 95% CI 3,020 to 6,122), and discharge to facility (adjusted OR 1.09, 95% CI 1.01 to 1.17). In contrast, septic shock with type 2 MI was associated with similar mortality and discharge to nursing facility and higher costs (adjusted parameter estimate 1,798, 95% CI 549 to 3,047). Septic shock hospitalizations with type 1 MI had higher in-hospital mortality (adjusted OR 1.74, 95% CI 1.60 to 1.90, p <0.001) compared with type 2 MI. In conclusion, type 1 MI is associated with higher mortality and resource utilization among septic shock hospitalizations. Furthermore, type 2 MI was associated with higher resource utilization., Competing Interests: Disclosures The authors have no conflicts of interest to declare., (Copyright © 2022. Published by Elsevier Inc.)

Background: The 2018 American Heart Association/American College of Cardiology/Multisociety cholesterol guideline states that statin therapy may be withheld or delayed among intermediate-risk individuals in the absence of coronary artery calcium (CAC=0). We evaluated whether traditional cardiovascular risk factors are associated with incident atherosclerotic cardiovascular disease (ASCVD) events among individuals with CAC=0 over long-term follow-up., Methods: We included participants with CAC=0 at baseline from the MESA (Multi-Ethnic Study of Atherosclerosis), a prospective cohort study of individuals free of clinical ASCVD at baseline. We used multivariable-adjusted Cox proportional hazards models to study the association between cardiovascular risk factors (cigarette smoking, diabetes, hypertension, preventive medication use [aspirin and statin], family history of premature ASCVD, chronic kidney disease, waist circumference, lipid and inflammatory markers) and adjudicated incident ASCVD outcomes., Results: We studied 3416 individuals (mean [SD] age 58 [9] years; 63% were female, 33% White, 31% Black, 12% Chinese American, and 24% Hispanic). Over a median follow-up of 16 years, there were 189 ASCVD events (composite of coronary heart disease and stroke) of which 91 were coronary heart disease, 88 were stroke, and 10 were both coronary heart disease and stroke events. The unadjusted event rates of ASCVD were ≤5 per 1000 person-years among individuals with CAC=0 for most risk factors with the exception of current cigarette smoking (7.3), diabetes (8.9), hypertension (5.4), and chronic kidney disease (6.8). After multivariable adjustment, risk factors that were significantly associated with ASCVD included current cigarette smoking: hazard ratio, 2.12 (95% CI, 1.32-3.42); diabetes: hazard ratio, 1.68 (95% CI, 1.01-2.80); and hypertension: hazard ratio, 1.57 (95% CI, 1.06-2.33)., Conclusions: Current cigarette smoking, diabetes, and hypertension are independently associated with incident ASCVD over a 16-year follow-up among those with CAC=0.

Background: Statin associated side effects (SASE) are a leading cause of statin discontinuation., Objective: We evaluated patient, provider, and facility characteristics associated with SASEs and whether these characteristics impact statin utilization., Methods: Patients with atherosclerotic cardiovascular disease (ASCVD) receiving care across the Veterans Affairs healthcare system from October 1, 2014 to September 30, 2015 were included. Multivariable logistic regression analyses were performed to determine (a) factors associated with SASE and (b) factors associated with statin use in those with SASE., Results: Our cohort included 1,225,576 patients with ASCVD. Of these, 171,189 (13.7%) had at least 1 reported SASE since year 2000. The most significant odds for SASEs were observed with female sex (odds ratio [OR] 1.40, 95% confidence interval [CI] 1.36, 1.45), White race (OR 1.43, 95% CI 1.41, 1.45), hypertension (OR 1.37, 95% CI 1.33, 1.41) and ischemic heart disease (IHD: OR 1.45, 95% CI 1.43, 1.47). Lower odds were noted with care at a teaching facility (OR 0.89, 95% CI 0.88, 0.90). Factors most associated with being on a statin among patients with SASE included having diabetes (OR 1.18, 95% CI 1.15, 1.20), IHD (OR 1.39, 95% CI 1.35, 1.43) and a higher number of cardiology visits (OR 1.08, 95% CI 1.07, 1.09), while female sex was associated with lower odds (OR 0.65, 95% CI 0.61, 0.69)., Conclusion: There are significant disparities in statin use by sex, ASCVD type, and comorbidities among secondary prevention patients with SASE, which represent areas for improvement in optimizing statin utilization., (Copyright © 2021. Published by Elsevier Inc.)

Rationale & Objective: Pulmonary hypertension (PH) is highly prevalent among patients with chronic kidney disease (CKD) not requiring kidney replacement therapy. We studied the associations of PH with mortality, kidney failure, as well as cardiovascular (CV) and non-CV hospitalization among Medicare beneficiaries with a CKD diagnosis., Study Design: Retrospective, observational study using a matched cohort design., Setting & Participants: Patients with PH (based on 2 claims within 2 years) and patients without PH matched on CKD stage from the Medicare 5% CKD sample (1996-2016)., Predictor: Presence of pulmonary hypertension., Outcome: Mortality, kidney failure, and all-cause, CV, and non-CV hospitalization., Analytical Approach: Cox proportional hazards models to assess the association between PH and mortality, adjusting for age, sex, race, and comorbidities. Death was considered as a competing event in Fine-Gray models to assess the association between PH and kidney failure. Negative binomial model was used to evaluate the relationship between PH and all-cause, CV, and non-CV hospitalizations., Results: 30,052 patients with PH and CKD and 150,260 CKD stage-matched patients without diagnosed PH were studied. The median age of the study population was 80.7 years, 57.8% were women, and 10.3% were African Americans. The presence of PH was associated with an increased risk of mortality after 1 (HR, 2.87 [95% CI, 2.79-2.95]), 2-3 (HR, 1.56 [95% CI, 1.51-1.61]), and 4-5 (HR, 1.47 [95% CI, 1.40-1.53]) years of follow-up, and a higher risk of all-cause, CV, and non-CV hospitalization during the same period. PH was also associated with kidney failure in after 1 and 2-3 years but not after 4-5 years of follow-up evaluation. Patients with PH also experienced higher rates of acute kidney injury (AKI), and AKI requiring dialysis support within 30 and 90 days of AKI., Limitations: Reliance on billing codes and lack of echocardiogram or right heart catheterization data CONCLUSIONS: Among older Medicare beneficiaries with a CKD diagnosis not requiring kidney replacement therapy, the presence of PH was associated with an increased risk of mortality, kidney failure, and hospitalization. Understanding of the mechanism of these associations, especially the increased risk of kidney failure, requires further study., (Published by Elsevier Inc.)

Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of morbidity and mortality in the United States (U.S.) and incurs significant cost to the healthcare system. Management of cholesterol remains central for ASCVD prevention and has been the focus of multiple national guidelines. In this review, we compare the American Heart Association (AHA)/American College of Cardiology (ACC) and the U.S. Department of Veterans Affairs (VA) and U.S. Department of Defense (DoD) Cholesterol guidelines. We review the evidence base that was used to generate recommendations focusing on 4 distinct themes: 1) the threshold of absolute 10-year ASCVD risk to start a clinician-patient discussion for the initiation of statin therapy in primary prevention patients; 2) the utility of coronary artery calcium score to guide clinician-patient risk discussion pertaining to the initiation of statin therapy for primary ASCVD prevention; 3) the use of moderate versus high-intensity statin therapy in patients with established ASCVD; and 4) the utility of ordering lipid panels after initiation or intensification of lipid lowering therapy to document efficacy and monitor adherence to lipid lowering therapy. We discuss why the VA/DoD and AHA/ACC may have reached different conclusions on these key issues., Competing Interests: Declaration of Competing Interest Salim S. Virani, Research support: Department of Veterans Affairs, World Heart Federation, Tahir and Jooma Family. Honorarium: American College of Cardiology (Associate Editor for Innovations, acc.org). Vijay Nambi, Site PI for study sponsored by AMGEN. Supported by VA MERIT award. Provisional patent along with BCM, Roche on use of biomarkers in prediction of Heart failure, (Published by Elsevier Inc.)

Background: Obesity and hypogonadism additively contribute to frailty in older men; however, appropriate treatment remains controversial., Objective: Determine whether testosterone replacement augments the effect of lifestyle therapy on physical function in older men with obesity and hypogonadism., Design: Randomized, double-blind, placebo-controlled trial., Setting: VA Medical Center., Participants: 83 older (age ≥65 years) men with obesity (body mass index ≥30 kg/m2) and persistently low am testosterone (<10.4 nmol/L) associated with frailty., Interventions: Participants were randomized to lifestyle therapy (weight management and exercise training) plus either testosterone (LT+Test) or placebo (LT+Pbo) for 6 months., Outcome Measures: Primary outcome was change in Physical Performance Test (PPT) score. Secondary outcomes included other frailty measures, body composition, hip bone mineral density (BMD), physical functions, hematocrit, prostate specific antigen (PSA), and sex hormones., Results: PPT score increased similarly in LT+Test and LT+Pbo group (17% vs. 16%; P = 0.58). VO2peak increased more in LT+Test than LT+Pbo (23% vs. 16%; P = 0.03). Despite similar -9% weight loss, lean body mass and thigh muscle volume decreased less in LT+Test than LT+Pbo (-2% vs. -3%; P = 0.01 and -2% vs -4%; P = 0.04). Hip BMD was preserved in LT+Test compared with LT+Pbo (0.5% vs -1.1%; P = 0.003). Strength increased similarly in LT+Test and LT+Pbo (23% vs 22%; P = 0.94). Hematocrit but not PSA increased more in LT+Test than LT+Pbo (5% vs 1%; P < 0.001). Testosterone levels increased more in LT+Test than LT+Pbo (167% vs 27%; P < 0.001)., Conclusion: In older, obese hypogonadal men, adding testosterone for 6 months to lifestyle therapy does not further improve overall physical function. However, our findings suggest that testosterone may attenuate the weight loss-induced reduction in muscle mass and hip BMD and may further improve aerobic capacity., (Published by Oxford University Press on behalf of the Endocrine Society 2020.)

Background: Although intensive blood pressure reduction has cardiovascular benefits, the absolute benefit is greater in those at higher cardiovascular disease (CVD) risk., Objectives: This study examined whether N-terminal pro-B-type natriuretic peptide (NT-proBNP) helps identify subjects at higher risk for CVD events across systolic blood pressure (SBP), diastolic blood pressure (DBP), or pulse pressure (PP) categories., Methods: Participants from the ARIC (Atherosclerosis Risk In Communities) study visit 4 (1996 to 98) were grouped according to SBP, DBP, or PP categories and further stratified by NT-proBNP categories. Cox regression models were used to estimate hazard ratios for incident CVD (coronary heart disease, ischemic stroke, or heart failure hospitalization) and mortality across combined NT-proBNP and/or BP categories, adjusting for CVD risk factors., Results: There were 9,309 participants (age: 62.6 ± 5.6 years; 58.3% women) with 2,416 CVD events over a median follow-up of 16.7 years. Within each SBP, DBP, or PP category, a higher category of NT-proBNP (100 to <300 or 300 pg/ml, compared with NT-proBNP <100 pg/ml) was associated with a graded increased risk for CVD events and mortality. Participants with SBP 130 to 139 mm Hg but NT-proBNP ≥300 pg/ml had a hazards ratio of 3.4 for CVD (95% confidence interval: 2.44 to 4.77) compared with a NT-proBNP of <100 pg/ml and SBP of 140 to 149 mm Hg., Conclusions: Elevated NT-proBNP is independently associated with CVD and mortality across SBP, DBP, and PP categories and helps identify subjects at the highest risk. Participants with stage 1 hypertension but elevated NT-proBNP had greater cardiovascular risk compared with those with stage 2 SBP but lower NT-proBNP. Future studies are needed to evaluate use of biomarker-based strategies for CVD risk assessment to assist with initiation or intensification of BP treatment., Competing Interests: Funding Support and Author Disclosures The ARIC study has been funded in whole or in part with federal funds from the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services (contract numbers: HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700005I, HHSN268201700004I). Dr. Selvin is supported by National Institutes of Health (grants K24-DK106414 and R01-DK089174). Drs. Selvin and Ballantyne are supported by National Institutes of Health (grant R01- HL134320). Dr Virani is supported by research support and a grant from Department of Veterans Affairs and World Heart Federation. Dr. Shah is supported by the National Institutes of Health (grants R01-HL135008, R01-HL143224, R01-HL150342, and K24-HL152008). Dr. Nambi is supported by a VA MERIT grant 1I01CX001112-01. Dr. de Lemos has received grant support and consulting income from Roche Diagnostics and Abbott Diagnostics; and has received consulting income from Ortho Clinical Diagnostics and Quidel Cardiovascular, Inc. Dr. Hoogeveen has received research grants (to his institution) and has been a consultant for Denka Seiken. Dr. Matsushita received nonfinancial research support from Roche Diagnostic Cooperation. Dr. Virani has received honorarium from the American College of Cardiology (Associate editor for Innovations acc.org); and has been a member of the Steering Committee for the PALM registry at Duke Clinical Research Institute (no financial remuneration). Dr Shah has received research support (significant; paid to institution, not individual) from Novartis; and has been a consultant (modest) for Philips Ultrasound. Dr. Selvin has received honoraria from Novo Nordisk. Dr. Ballantyne has received grants or research support (to his institution) from Abbott Diagnostic, Akcea, Amgen, Esperion, Novartis, Regeneron, and Roche Diagnostic; and has been a consultant for Abbott Diagnostics, Akcea, Amarin, Amgen, AstraZeneca, Boehringer Ingelheim, Corvidia, Denka Seiken, Esperion, Intercept, Janssen, Matinas BioPharma Inc., Merck, Novartis, Novo Nordisk, Regeneron, Roche Diagnostic, and Sanofi-Synthelabo. Drs. Ballantyne and Nambi are named on provisional patent no. 61721475 “Biomarkers to Improve Prediction of Heart Failure Risk” filed by Baylor College of Medicine and Roche. Dr. Nambi has been a site principal investigator for a study sponsored by Merck and Amgen. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Published by Elsevier Inc.)

Background Sudden cardiac death (SCD) is associated with severe coronary heart disease in the great majority of cases. Whether carotid intima-media thickness (C-IMT), a known surrogate marker of subclinical atherosclerosis, is associated with risk of SCD in a general population remains unknown. The objective of this study was to investigate the association between C-IMT and risk of SCD. Methods and Results We examined a total of 20 862 participants: 15 307 participants of the ARIC (Atherosclerosis Risk in Communities) study and 5555 participants of the CHS (Cardiovascular Health Study). C-IMT and common carotid artery intima-media thickness was measured at baseline by ultrasound. Presence of plaque was judged by trained readers. Over a median of 23.5 years of follow-up, 569 participants had SCD (1.81 cases per 1000 person-years) in the ARIC study. Mean C-IMT and common carotid artery intima-media thickness were associated with risk of SCD after adjustment for traditional risk factors and time-varying adjustors: hazard ratios (HRs) with 95% CIs for fourth versus first quartile were 1.64 (1.15-2.63) and 1.49 (1.05-2.11), respectively. In CHS, 302 participants developed SCD (4.64 cases per 1000 person-years) over 13.1 years. Maximum C-IMT was associated with risk of SCD after adjustment: HR (95% CI) for fourth versus first quartile was 1.75 (1.22-2.51). Presence of plaque was associated with 35% increased risk of SCD: HR (95% CI) of 1.37 (1.13-1.67) in the ARIC study and 1.32 (1.04-1.68) in CHS. Conclusions C-IMT was associated with risk of SCD in 2 biracial community-based cohorts. C-IMT may be used as a marker of SCD risk and potentially to initiate early therapeutic interventions to mitigate the risk.

Background: It is important to study the trends of e-cigarette use among various subgroups to understand which populations may be more susceptible to increased use and, therefore, are at risk for potential long-term health effects., Methods: We used cross-sectional data from the 2016-2017 Behavioral Risk Factor Surveillance System, a nationally representative U.S. telephone-based survey of adults aged 18 years or older. The 2017 dataset also includes data from participant interviews that had been conducted in the year 2018. Current e-cigarette use was defined as use of e-cigarettes every day or on some days. We analyzed data using survey weights to ensure representativeness of the data to the US population., Results: The study population consisted of 936,319 individuals, of whom 28,917 were current e-cigarette users, and corresponded to 10.8 million U.S. adults. Thirty percent were aged between 18 and 34 years. Forty-nine percent were men; 63% were white, 12% black, and 17% Hispanic. The overall prevalence of current e-cigarette use increased from 4.3% in 2016 to 4.8% in 2018. E-cigarette use significantly increased among middle-aged adults (from 3.9% to 5.2%; P = .004), women (from 3.3% to 4.3%; P <.001), and former smokers (from 5.2% to 7.9%; P = .02), but decreased among current smokers (from 14.5% to 13.8%; P = .02)., Conclusions: In a nationally representative sample, we found important trends in e-cigarette use in a relatively short time frame. A significantly increasing prevalence of e-cigarette use was noted among middle-age adults, women, and former smokers. Our study provides important information about e-cigarette trends that can be used by clinicians when counselling patients and by regulatory agencies to develop public policies., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: Inflammatory markers, such as hs-CRP (high-sensitivity C-reactive protein), have been reported to be related to peripheral artery disease (PAD). Galectin-3, a biomarker of fibrosis, has been linked to vascular remodeling and atherogenesis. However, its prospective association with incident PAD is unknown; as is the influence of inflammation on the association between galectin-3 and PAD. Approach and Results: In 9851 Atherosclerosis Risk in Communities Study participants free of PAD at baseline (1996-1998), we quantified the association of galactin-3 and hs-CRP with incident PAD (hospitalizations with PAD diagnosis [ International Classification of Diseases - Ninth Revision : 440.2-440.4] or leg revascularization [eg, International Classification of Diseases - Ninth Revision : 38.18]) as well as its severe form, critical limb ischemia (PAD cases with resting pain, ulcer, gangrene, or leg amputation) using Cox models. Over a median follow-up of 17.4 years, there were 316 cases of PAD including 119 critical limb ischemia cases. Log-transformed galectin-3 was associated with incident PAD (adjusted hazard ratio, 1.17 [1.05-1.31] per 1 SD increment) and critical limb ischemia (1.25 [1.05-1.49] per 1 SD increment). The association was slightly attenuated after further adjusting for hs-CRP (1.14 [1.02-1.27] and 1.22 [1.02-1.45], respectively). Log-transformed hs-CRP demonstrated robust associations with PAD and critical limb ischemia even after adjusting for galectin-3 (adjusted hazard ratio per 1 SD increment 1.34 [1.18-1.52] and 1.34 [1.09-1.65], respectively). The addition of galectin-3 and hs-CRP to traditional atherosclerotic predictors (C statistic of the base model 0.843 [0.815-0.871]) improved the risk prediction of PAD (ΔC statistics, 0.011 [0.002-0.020])., Conclusions: Galectin-3 and hs-CRP were independently associated with incident PAD in the general population, supporting the involvement of fibrosis and inflammation in the pathophysiology of PAD.

Atherosclerotic plaque detection by carotid ultrasound provides cardiovascular disease risk stratification. The advantages and disadvantages of two-dimensional (2D) and three-dimensional (3D) ultrasound methods for carotid arterial plaque quantification are reviewed. Advanced and emerging methods of carotid arterial plaque activity and composition analysis by ultrasound are considered. Recommendations for the standardization of focused 2D and 3D carotid arterial plaque ultrasound image acquisition and measurement for the purpose of cardiovascular disease stratification are formulated. Potential clinical application towards cardiovascular risk stratification of recommended focused carotid arterial plaque quantification approaches are summarized., (Copyright © 2020 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Background Circulating galectin-3 levels provide prognostic information in patients with established heart failure (HF), but the associations between galectin-3 levels and other incident cardiovascular events in asymptomatic individuals at midlife and when remeasured ≈15 years later are largely uncharacterized. Methods and Results Using multivariable Cox proportional hazards models, we identified associations between plasma galectin-3 levels (hazard ratio [HR] per 1 SD increase in natural log galectin-3) and incident coronary heart disease, ischemic stroke, HF hospitalization, and total mortality in ARIC (Atherosclerosis Risk in Communities) participants free of cardiovascular disease at ARIC visit 4 (1996-1998; n=9247) and at ARIC visit 5 (2011-2013; n=4829). Higher galectin-3 level at visit 4 (median age 62) was independently associated with incident coronary heart disease (adjusted HR, 1.30; 95% CI, 1.06-1.60), ischemic stroke (HR, 1.42; 95% CI, 1.01-2.00), HF (HR, 1.44; 95% CI, 1.17-1.76), and mortality (HR, 1.56; 95% CI, 1.35-1.80). At visit 5 (median age, 74), higher galectin-3 level was associated with incident HF (HR, 1.93; 95% CI, 1.15-3.24) and total mortality (HR, 1.70; 95% CI, 1.15-2.52), but not coronary heart disease or stoke. Individuals with the greatest increase in galectin-3 levels from visit 4 to visit 5 were also at increased risk of incident HF and total mortality. Conclusions In a large, biracial community-based cohort, galectin-3 measured at midlife and older age was associated with increased risk of cardiovascular events. An increase in galectin-3 levels over this period was also associated with increased risk.

Background: Limited data exist on the association of obesity with both hospitalization and mortality in patients with heart failure with preserved ejection fraction (HFpEF), especially in the real-world ambulatory setting. We hypothesized that increasing body-mass index (BMI) in ambulatory heart failure with preserved ejection fraction would have a protective effect on these patients leading to decreased mortality and hospitalizations., Methods: We studied the relationship between BMI and the time to all-cause mortality, time to heart failure (HF) hospitalization, and time to all-cause hospitalization over a 2-year follow-up in a national cohort of 2501 ambulatory HFpEF patients at 153 Veterans Affairs medical centers., Results: Compared with normal BMI, overweight (HR 0.72; 95% CI 0.57-0.91), obesity class I (HR 0.59; 95% CI 0.45-0.77), obesity class II (HR 0.56; 95% CI 0.40-0.77), and obesity class III (HR 0.53; 95% CI 0.36-0.77) were associated with improved survival after adjustment for demographics and comorbidities. In contrast, the time to HF hospitalization showed an inverse relationship, with shorter time to HF hospitalization with increasing BMI compared with normal BMI; overweight (adjusted HR 1.30; 95% CI 0.88-1.90), obesity class I (HR 1.57; 95% CI 1.05-2.34), obesity class II (HR 1.79; 95% CI 1.15-2.78), and obesity class III (HR 1.96; 95% CI 1.23-3.12). However, time to first all-cause hospitalization was not significantly different by BMI groups., Conclusions: In a large, national ambulatory HFpEF cohort, despite the presence of the obesity paradox with respect to survival, increasing BMI was independently associated with an increased risk of HF hospitalization and similar risk of all-cause hospitalization. Future longer-term prospective trials evaluating the safety and efficacy of weight loss on morbidity and mortality, in patients with severe obesity and HFpEF are needed.

Background Greater physical activity (PA) is associated with lower heart failure (HF) risk. However, it is unclear whether this inverse association exists across all subgroups at high risk for HF, particularly among those with preexisting atherosclerotic cardiovascular disease. Methods and Results We followed 13 810 ARIC (Atherosclerosis Risk in Communities) study participants (mean age 55 years, 54% women, 26% black) without HF at baseline (visit 1; 1987-1989). PA was assessed using a modified Baecke questionnaire and categorized according to American Heart Association guidelines: recommended, intermediate, or poor. We constructed Cox models to estimate associations between PA categories and incident HF within each high-risk subgroup at baseline, with tests for interaction. We performed additional analyses modeling incident coronary heart disease as a time-varying covariate. Over a median of 26 years of follow-up, there were 2994 HF events. Compared with poor PA, recommended PA was associated with lower HF risk among participants with hypertension, obesity, diabetes mellitus, and metabolic syndrome (all P <0.01), but not among those with prevalent atherosclerotic cardiovascular disease (coronary heart disease, stroke, or peripheral arterial disease) (hazard ratio, 0.91; 95% CI, 0.74-1.13 [ P interaction=0.02]). Recommended PA was associated with lower risk of incident coronary heart disease (hazard ratio, 0.79; 95% CI, 0.72-0.86), but not with lower HF risk in those with interim coronary heart disease events (hazard ratio, 0.90; 95% CI, 0.78-1.04 [ P interaction=0.04]). Conclusions PA was associated with decreased HF risk in patients with hypertension, obesity, diabetes mellitus, and metabolic syndrome. Despite a myriad of benefits in patients with atherosclerotic cardiovascular disease, PA may have weaker associations with HF prevention after ischemic disease is established.

Treatment guidelines recommend monitoring of lipids to assess efficacy and adherence to lipid lowering therapy. We assessed whether lipid profile monitoring is associated with intensification of cholesterol lowering therapy. Patients from the Veterans Affairs (VA) healthcare system with atherosclerotic cardiovascular disease and at least one primary care visit between October 2013 and September 2014 were included (n = 1,061,753). Treatment intensification was defined as the initiation of a statin, an increase in the intensity or dose of statin therapy and/or the addition of ezetimibe. An association between the number of lipid panels and treatment intensification was assessed with adjusted regression models. During the study period, 87.1% of included patients had ≥1 lipid panel. Patients with ≥1 lipid panel were more likely to undergo treatment intensification compared with individuals with 0 lipid panels (9.3% vs 5.4%, respectively, p <0.001). Among individuals not on statin therapy at the index date (n = 287,636), those with ≥1 lipid panel were more likely to have a statin initiated compared those who without a lipid panel (21.5% vs 8.7%, p <0.001). On regression analysis (odds ratio [OR] [95% confidence interval {CI}]), patients with 1 lipid panel (1.55 [1.50 to 1.59]), 2 to 3 lipid panels (1.76 [1.71 to 1.81]) and >3 lipid panels (3.02 [2.90 to 3.14]) showed greater odds of treatment intensification compared with individuals without a lipid panel. In conclusion, lipid monitoring is associated with higher rates of treatment intensification in patients with atherosclerotic cardiovascular disease. This has important clinical implications as higher intensity regimens with statins and in combination with select nonstatin therapies is associated with improved cardiovascular outcomes., (Published by Elsevier Inc.)

Background: Risk for atherosclerotic cardiovascular disease was a novel consideration for antihypertensive medication initiation in the 2017 American College of Cardiology/American Heart Association Blood Pressure (BP) guideline. Whether biomarkers of chronic myocardial injury (high-sensitivity cardiac troponin T ≥6 ng/L] and stress (N-terminal pro-B-type natriuretic peptide [NT-proBNP] ≥100 pg/mL) can inform cardiovascular (CV) risk stratification and treatment decisions among adults with elevated BP and hypertension is unclear., Methods: Participant-level data from 3 cohort studies (Atherosclerosis Risk in Communities Study, Dallas Heart Study, and Multiethnic Study of Atherosclerosis) were pooled, excluding individuals with prevalent CV disease and those taking antihypertensive medication at baseline. Participants were analyzed according to BP treatment group from the 2017 American College of Cardiology/American Heart Association BP guideline and those with high BP (120 to 159/<100 mm Hg) were further stratified by biomarker status. Cumulative incidence rates for CV event (atherosclerotic cardiovascular disease or heart failure), and the corresponding 10-year number needed to treat to prevent 1 event with intensive BP lowering (to target systolic BP <120 mm Hg), were estimated for BP and biomarker-based subgroups., Results: The study included 12 987 participants (mean age, 55 years; 55% women; 21.5% with elevated high-sensitivity cardiac troponin T; 17.7% with elevated NT-proBNP) with 825 incident CV events over 10-year follow-up. Participants with elevated BP or hypertension not recommended for antihypertensive medication with versus without either elevated high-sensitivity cardiac troponin T or NT-proBNP had a 10-year CV incidence rate of 11.0% and 4.6%, with a 10-year number needed to treat to prevent 1 event for intensive BP lowering of 36 and 85, respectively. Among participants with stage 1 or stage 2 hypertension recommended for antihypertensive medication with BP <160/100 mm Hg, those with versus without an elevated biomarker had a 10-year CV incidence rate of 15.1% and 7.9%, with a 10-year number needed to treat to prevent 1 event of 26 and 49, respectively., Conclusions: Elevations in high-sensitivity cardiac troponin T or NT-proBNP identify individuals with elevated BP or hypertension not currently recommended for antihypertensive medication who are at high risk for CV events. The presence of nonelevated biomarkers, even in the setting of stage 1 or stage 2 hypertension, was associated with lower risk. Incorporation of biomarkers into risk assessment algorithms may lead to more appropriate matching of intensive BP control with patient risk.

Objectives: Cardiac troponin T, measured using a high-sensitive assay (hs-cTnT), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are associated with increased stroke risk and perhaps with cognitive decline. However, few well-designed prospective studies with extended follow-up have been conducted. We aimed to estimate the association of hs-cTnT and NT-proBNP with 15-year cognitive change in the Atherosclerosis Risk in Communities (ARIC) study., Design: Prospective cohort study., Setting: Four US communities., Participants: A total of 9114 and 9108 participants from the Atherosclerosis Risk in Communities study for analyses of hs-cTnT and NT-proBNP, respectively., Measurements: We examined association of hs-cTnT and NT-proBNP with 15-year change (1996-1998 to 2011-2013) in three cognitive tests of executive function (Digit Symbol Substitution Test), verbal learning memory (Delayed Word Recall Test), and semantic fluency (Word Fluency Test), and an overall score combining the three tests using multivariable linear mixed effect models. We conducted several sensitivity analyses including multiple imputations to address bias due to missing data and attrition, and we compared associations within groups combining hs-cTnT and NT-proBNP into a three-level categorical variable., Results: At baseline (1996-1998), mean age was 63.4 (standard deviation [SD] = 5.7) years; 56.4% were women, and 17.5% were black. The hs-cTnT at baseline was not associated with cognitive change in any measure. Some evidence indicated accelerated decline in verbal learning and memory when comparing those in the highest with the lowest NT-proBNP quintiles; however, this association was not replicated when considering clinically relevant cutoffs or deciles of exposure in survivors. Sensitivity analyses were consistent with our primary analyses. There was little evidence to support effect modification by any considered factors. People with highest levels of both biomarkers had excessive decline in global z scores vs people with lowest levels (-.34; 95% confidence interval = -.63 to -.04)., Conclusion: Markers of myocardial injury and stretch were not associated with cognitive decline following 15 years among survivors, but when combined together they were suggestive in post hoc analysis. Whether this represents targets of intervention should be examined in the future. J Am Geriatr Soc 67:2353-2361, 2019., (© 2019 The American Geriatrics Society.)

Background: High-sensitivity cardiac troponin T (hs-cTnT) is individually associated with incident hypertension (HTN) and cardiovascular disease (CVD) events. We hypothesize that the increases in hs-cTnT with increases in blood pressure will be related to higher incidence of CVD., Methods: The Cardiovascular Health Study is a longitudinal cohort of older adults. Those with hs-cTnT data and CVD risk factors at baseline and follow-up (2-3 years later) were stratified based on systolic blood pressure (SBP; optimal: <120 mm Hg, intermediate: 120-139 mm Hg, elevated: ≥140 mm Hg) and hs-cTnT (undetectable: <5 ng/l, detectable: 5-13 ng/l, elevated: ≥14 ng/l) categories. SBP and hs-cTnT were classified as increased or decreased if they changed categories between exams, and stable if they did not. Cox regression evaluated incident CVD events over an average 9-year follow-up., Results: Among 2,219 adults, 510 (23.0 %) had decreased hs-cTnT, 1,279 (57.6 %) had stable hs-cTnT, and 430 (19.4 %) had increased hs-cTnT. Those with increased hs-cTnT had a higher CVD risk with stable SBP (hazard ratio [HR]: 1.28 [1.04-1.57], P = 0.02) or decreased SBP (HR: 1.57 [1.08-2.28], P = 0.02) compared to those within the same SBP group but a stable hs-cTnT. In those with lower SBP at follow-up, there was an inverse relation between diastolic blood pressure (DBP) and risk of CVD events in those with increased hs-cTnT (HR: 0.44 per 10 mm Hg increase, P < 0.01)., Conclusion: An increase in hs-cTnT over time is associated with a higher risk of CVD even when the blood pressure is stable or decreases over time., (© American Journal of Hypertension, Ltd 2019. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Measurement with a lipid panel after statin initiation and in long-term follow-up is recommended in both 2013 and 2018 cholesterol guidelines to assess statin efficacy and adherence. We assessed whether routine laboratory evaluation with lipid panels is associated with greater statin adherence., Methods: We identified patients with atherosclerotic cardiovascular disease within the entire Veterans Affairs (VA) health care system with at least one primary care visit between October 2013 and September 2014, who were on statin therapy (n = 813,887; n = 52,583 for new statin users). Statin adherence was determined using medication refill data and assessed by proportion of days covered (PDC). Association between number of lipid panels completed and PDC was assessed with adjusted regression models., Results: Within the study period, the mean number of lipid panels that were completed per patient was 1.5 ± 1.0. In the overall cohort, percentage of statin users with PDC ≥80% was 66.0% for patients with ≥1 lipid panel and 61.2% for patients with 0 lipid panels (P < .0001). Among new statin users, PDC ≥80% was 68.0% for patients with lipid panels completed within 4-12 weeks of therapy initiation and 59.3% for those without lipid panels completed within the timeframe (P < .0001). In adjusted analysis, number of lipid panels completed was associated with a modest but significant increase in PDC, when PDC was evaluated as a continuous (beta-coefficient 0.0054, P < .001) or categorical (PDC ≥80% [odds ratio (OR) 1.01; 95% confidence interval (CI), 1.00-1.01]) measure of statin adherence. The significant association was also observed in new users (beta-coefficient 0.0058, P < .001; OR 1.02; 95% CI, 1.00-1.03)., Conclusion: Routine, guideline-directed completion of lipid panels in atherosclerotic cardiovascular disease patients on statins overall and among new statin users is associated with a modes6t but significant increase in statin adherence., (Published by Elsevier Inc.)

Background: We assessed whether plasma troponin I measured by a high-sensitivity assay (hs-TnI) is associated with incident cardiovascular disease (CVD) and mortality in a community-based sample without prior CVD., Methods: ARIC study (Atherosclerosis Risk in Communities) participants aged 54 to 74 years without baseline CVD were included in this study (n=8121). Cox proportional hazards models were constructed to determine associations between hs-TnI and incident coronary heart disease (CHD; myocardial infarction and fatal CHD), ischemic stroke, atherosclerotic CVD (CHD and stroke), heart failure hospitalization, global CVD (atherosclerotic CVD and heart failure), and all-cause mortality. The comparative association of hs-TnI and high-sensitivity troponin T with incident CVD events was also evaluated. Risk prediction models were constructed to assess prediction improvement when hs-TnI was added to traditional risk factors used in the Pooled Cohort Equation., Results: The median follow-up period was ≈15 years. Detectable hs-TnI levels were observed in 85% of the study population. In adjusted models, in comparison to low hs-TnI (lowest quintile, hs-TnI ≤1.3 ng/L), elevated hs-TnI (highest quintile, hs-TnI ≥3.8 ng/L) was associated with greater incident CHD (hazard ratio [HR], 2.20; 95% CI, 1.64-2.95), ischemic stroke (HR, 2.99; 95% CI, 2.01-4.46), atherosclerotic CVD (HR, 2.36; 95% CI, 1.86-3.00), heart failure hospitalization (HR, 4.20; 95% CI, 3.28-5.37), global CVD (HR, 3.01; 95% CI, 2.50-3.63), and all-cause mortality (HR, 1.83; 95% CI, 1.56-2.14). hs-TnI was observed to have a stronger association with incident global CVD events in white than in black individuals and a stronger association with incident CHD in women than in men. hs-TnI and high-sensitivity troponin T were only modestly correlated ( r=0.47) and were complementary in prediction of incident CVD events, with elevation of both troponins conferring the highest risk in comparison with elevation in either one alone. The addition of hs-TnI to the Pooled Cohort Equation model improved risk prediction for atherosclerotic CVD, heart failure, and global CVD., Conclusions: Elevated hs-TnI is strongly associated with increased global CVD incidence in the general population independent of traditional risk factors. hs-TnI and high-sensitivity troponin T provide complementary rather than redundant information.

Background: Ticagrelor is a P2Y 12 receptor inhibitor with superior clinical efficacy compared with clopidogrel. However, it is associated with reduced efficacy when combined with a high-dose aspirin., Methods and Results: Patients in the acute coronary treatment and intervention outcomes network (ACTION) Registry-Get With The Guidelines (GWTG) with acute myocardial infarction from October 2013 through December 2014 were included in the study (167 455 patients; 622 sites). We evaluated temporal trends in the prescription of P2Y 12 inhibitors, and identified factors associated with ticagrelor use at discharge. Among patients discharged on ticagrelor and aspirin (21 262 patients), we evaluated the temporal trends and independent factors associated with high-dose aspirin prescription at discharge. Ticagrelor prescription at discharge increased significantly from 12% to 16.7% ( P <0.0001). Decreases in prasugrel and clopidogrel use at discharge (15.7%-13.9% and 54.2%-51.1%, respectively, P <0.0001) were also observed. Independent factors associated with preferential ticagrelor prescription at discharge over clopidogrel included younger age, white race, home ticagrelor use, invasive management, and in-hospital re-infarction and stroke ( P <0.0001 for all), whereas older age, female sex, prior stroke, home ticagrelor use, and in-hospital stroke ( P <0.0001 for all) were associated with preferential ticagrelor prescription at discharge over prasugrel. High-dose aspirin was used in 3.1% of patients discharged on ticagrelor. Independent factors associated with high-dose aspirin prescription at discharge included home aspirin use, diabetes mellitus, previous myocardial infarction, previous coronary artery bypass graft, ST-segment-elevation myocardial infarction, cardiogenic shock, and geographic region ( P =0.01)., Conclusions: Our contemporary analysis shows a modest but significant increase in the use of ticagrelor and a high rate of adherence to the use of low-dose aspirin at discharge., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Purpose: Cardiovascular diseases (CVDs) are a leading cause of morbidity and mortality worldwide, necessitating major efforts in prevention. This review summarizes the currently available training opportunities in CVD prevention for fellows-in-training (FITs) and residents. We also highlight the challenges and future directions for CVD prevention as a field and propose a structure for an inclusive CVD prevention training program., Recent Findings: At present, there is a lack of centralized training resources for FITs and residents interested in pursuing a career in CVD prevention. Training in CVD prevention is not an accredited subspecialty fellowship by the American Council of Graduate Medical Education (ACGME). Although there are several independent training programs under the broad umbrella of CVD prevention focusing on different aspects of prevention, there is no unified curriculum or training. More collaborative efforts are needed to identify CVD prevention as an ACGME-accredited subspecialty fellowship. Providing more resources can encourage and produce more leaders in this essential field.

Importance: The 2013 American College of Cardiology/American Heart Association (ACC/AHA) Cholesterol Management Guideline recommends moderate-intensity to high-intensity statin therapy in eligible patients., Objective: To examine adoption of the 2013 ACC/AHA guideline in US cardiology practices., Design, Setting, and Participants: Among 161 cardiology practices, trends in the use of moderate-intensity to high-intensity statin and nonstatin lipid-lowering therapy (LLT) were analyzed before (September 1, 2012, to November 1, 2013) and after (February 1, 2014, to April 1, 2015) publication of the 2013 ACC/AHA guideline among 4 mutually exclusive risk groups within the ACC Practice Innovation and Clinical Excellence Registry. Interrupted time series analysis was used to evaluate for differences in trend in use of moderate-intensity to high-intensity statin and nonstatin LLT use in hierarchical logistic regression models. Participants were a population-based sample of 1 105 356 preguideline patients (2 431 192 patient encounters) and 1 116 472 postguideline patients (2 377 219 patient encounters). Approximately 97% of patients had atherosclerotic cardiovascular disease (ASCVD)., Exposures: Moderate-intensity to high-intensity statin and nonstatin LLT use before and after publication of the 2013 ACC/AHA guideline., Main Outcomes and Measures: Time trend in the use of moderate-intensity to high-intensity statin and nonstatin LLT., Results: In the study cohort, the mean (SD) age was 69.6 (12.1) years among 1 105 356 patients (40.2% female) before publication of the guideline and 70.0 (11.9) years among 1 116 472 patients (39.8% female) after publication of the guideline. Although there was a trend toward increasing use of moderate-intensity to high-intensity statins overall and in the ASCVD cohort, such a trend was already present before publication of the guideline. No significant difference in trend in the use of moderate-intensity to high-intensity statins was observed in other groups. The use of moderate-intensity to high-intensity statin therapy was 62.1% (before publication of the guideline) and 66.6% (after publication of the guideline) in the overall cohort, 62.7% (before publication) and 67.0% (after publication) in the ASCVD cohort, 50.6% (before publication) and 52.3% (after publication) in the cohort with elevated low-density lipoprotein cholesterol levels (ie, ≥190 mg/dL), 52.4% (before publication) and 55.2% (after publication) in the diabetes cohort, and 41.9% (before publication) and 46.9% (after publication) in the remaining group with 10-year ASCVD risk of 7.5% or higher. In hierarchical logistic regression models, there was a significant increase in the use of moderate-intensity to high-intensity statins in the overall cohort (4.8%) and in the ASCVD cohort (4.3%) (P < .01 for slope for both). There was no significant change for other risk cohorts. Nonstatin LLT use remained unchanged in the preguideline and postguideline periods in the hierarchical logistic regression models for all of the risk groups., Conclusions and Relevance: Adoption of the 2013 ACC/AHA Cholesterol Management Guideline in cardiology practices was modest. Timely interventions are needed to improve guideline-concordant practice to reduce the burden of ASCVD.

Purpose: In the IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT), simvastatin/ezetimibe combination was associated with a 6% relative risk reduction in the combined cardiovascular outcome compared with simvastatin alone in patients with acute coronary syndrome. Given strict inclusion criteria (low-density lipoprotein cholesterol 50-125 mg/dL and no use of statins more potent than simvastatin 40 mg), the implications of this important trial in routine acute coronary syndrome care are unknown., Methods: We identified patients with acute coronary syndrome from the Veterans Affairs health care system over a 5-year period and determined what proportion would be candidates for ezetimibe on the basis of IMPROVE-IT criteria. We then evaluated what proportion could potentially see an increase in ezetimibe use if IMPROVE-IT criteria are not strictly followed., Results: Of 219,625 patients with acute coronary syndrome, 69,508 (31.6%) would qualify for ezetimibe on the basis of strict criteria. Among those who did not meet IMPROVE-IT criteria (n = 150,117), ezetimibe could potentially be prescribed by clinicians in a further 28% of patients (n = 61,635) using statins more potent than simvastatin 40 mg, 7.1% of patients (15,527) with a documented statin intolerance, and 10.4% of patients (22,758) with low-density lipoprotein cholesterol >125 mg/dL., Conclusions: Our results provide a first look at the implications of this trial in a large health care system. Although 31.6% of patients would qualify for ezetimibe, there is a large potential for an increase in ezetimibe use in acute coronary syndrome outside of the strict trial inclusions. These findings call for a discussion on ezetimibe's role in patients with acute coronary syndrome already taking high-intensity statins or those with statin intolerance., (Published by Elsevier Inc.)

Background: Among patients without cardiovascular disease (CVD) and low 10-year CVD risk, the risks of gastrointestinal bleeding and hemorrhagic strokes associated with aspirin use outweigh any potential atheroprotective benefit. According to the guidelines on primary prevention of CVD, aspirin use is considered appropriate only in patients with 10-year CVD risk ≥6% and inappropriate in patients with 10-year CVD risk <6%., Objectives: The goal of this study was to examine the frequency and practice-level variation in inappropriate aspirin use for primary prevention in a large U.S. nationwide registry., Methods: Within the National Cardiovascular Disease Registry's Practice Innovation and Clinical Excellence registry, we assessed 68,808 unique patients receiving aspirin for primary prevention from 119 U.S. practices. The frequency of inappropriate aspirin use was determined for primary prevention (aspirin use in those with 10-year CVD risk <6%). Using hierarchical regression models, the extent of practice-level variation using the median rate ratio (MRR) was assessed., Results: Inappropriate aspirin use frequency was 11.6% (7,972 of 68,808) in the overall cohort. There was significant practice-level variation in inappropriate use (range 0% to 71.8%; median 10.1%; interquartile range 6.4%) for practices; adjusted MRR was 1.63 (95% confidence interval [CI]: 1.47 to 1.77). Results remained consistent after excluding 21,052 women age ≥65 years (inappropriate aspirin use 15.2%; median practice-level inappropriate aspirin use 13.8%; interquartile range 8.2%; adjusted MRR 1.61 [95% CI: 1.46 to 1.75]) and after excluding patients with diabetes (inappropriate aspirin use 13.9%; median practice-level inappropriate aspirin use 12.4%; interquartile range 7.6%; adjusted MRR 1.55 [95% CI: 1.41 to 1.67])., Conclusions: More than 1 in 10 patients in this national registry were receiving inappropriate aspirin therapy for primary prevention, with significant practice-level variations. Our findings suggest that there are important opportunities to improve evidence-based aspirin use for the primary prevention of CVD., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Based on observational studies, there is a linear increase in cardiovascular risk with higher systolic blood pressure (SBP), yet clinical trials have not shown benefit across all SBP categories. We assessed whether troponin T measured using high-sensitivity assay was associated with cardiovascular disease within SBP categories in 11 191 Atherosclerosis Risk in Communities study participants. Rested sitting SBP by 10-mm Hg increments and troponin categories were identified. Incident heart failure hospitalization, coronary heart disease, and stroke were ascertained for a median of 12 years after excluding individuals with corresponding disease. Approximately 53% of each type of cardiovascular event occurred in individuals with SBP<140 mm Hg and troponin T ≥3 ng/L. Higher troponin T was associated with increasing cardiovascular events across most SBP categories. The association was strongest for heart failure and least strong for stroke. There was no similar association of SBP with cardiovascular events across troponin T categories. Individuals with troponin T ≥3 ng/L and SBP <140 mm Hg had higher cardiovascular risk compared with those with troponin T <3 ng/L and SBP 140 to 159 mm Hg. Higher troponin T levels within narrow SBP categories portend increased cardiovascular risk, particularly for heart failure. Individuals with lower SBP but measurable troponin T had greater cardiovascular risk compared with those with suboptimal SBP but undetectable troponin T. Future trials of systolic hypertension may benefit by using high-sensitivity troponin T to target high-risk patients., (© 2014 American Heart Association, Inc.)

Retired National Football League (NFL) linemen have an increased prevalence of risk factors for atherosclerosis and have an increased risk of cardiovascular death compared with nonlinemen and the general population. We evaluated whether playing in lineman position is independently associated with an increased risk of the presence and severity of subclinical atherosclerosis. Players were categorized as linemen if they reported playing on the offensive or defensive line during their careers. Subclinical atherosclerosis was assessed using coronary artery calcium (CAC) scores in 931 retired NFL players (310 linemen, 621 nonlinemen). CAC scores were evaluated for absence of subclinical atherosclerosis (CAC = 0), presence of mild subclinical atherosclerosis (CAC 1 to 100), and moderate to severe subclinical atherosclerosis (CAC ≥100). We performed multivariate logistic regression to determine whether the lineman position is independently associated with the presence and severity of subclinical atherosclerosis. Linemen were noted to have a lesser likelihood of absence of subclinical atherosclerosis (CAC = 0, 33.8% vs 41.7%, p = 0.02), a similar likelihood of mild subclinical atherosclerosis (CAC 1 to 100, 33.2% vs 31.8%, p = 0.7), and a greater likelihood of moderate to severe subclinical atherosclerosis (CAC >100, 32.9% vs 26.4%, p = 0.04) compared with nonlinemen. Adjusting for demographic and metabolic covariates, lineman status remained independently associated with mild subclinical atherosclerosis (CAC 1 to 100, odds ratio [OR] 1.41, 95% confidence interval [CI] 1.05 to 2.2, p = 0.04) and moderate to severe subclinical atherosclerosis (CAC ≥100, OR 1.67, 95% CI 1.05 to 2.2). The association was attenuated after adjustment for race (CAC 1 to 100, OR 1.24, 95% CI 0.82 to 1.8; CAC >100, OR 1.59, 95% CI 1.01 to 2.49). In conclusion, lineman status in retired NFL players is associated with presence and severity of subclinical atherosclerosis, which is partly explained by race., (Copyright © 2014 Elsevier Inc. All rights reserved.)

It is not known whether genetic variants in the cholesteryl ester transfer protein (CETP) gene are associated with recurrent coronary heart disease events or mortality in secondary prevention patients. Among 3,717 patients with acute coronary syndrome or coronary artery bypass grafting (CABG) enrolled in a prospective genetic registry, we evaluated whether CETP gene variants previously shown to be associated with reduced CETP activity and high-density lipoprotein cholesterol increase ("A" allele for both TaqIB [rs708272] and rs12149545) are associated with a reduction in recurrent myocardial infarction (MI), recurrent revascularization, or death. At 4.5 years of follow-up, 439 recurrent MI, 698 recurrent revascularizations, and 756 deaths occurred. Using an additive model of inheritance, the "A" allele for rs708272 was not associated with recurrent MI (hazard ratio [HR] 0.95, 95% confidence interval [CI] 0.78 to 1.17 for AG; HR 0.89, 95% CI 0.67 to 1.19 for AA; compared with GG genotype), recurrent revascularization (HR 1.13, 95% CI 0.95 to 1.33 for AG; HR 1.05, 95% CI 0.84 to 1.32 for AA), or mortality (HR 1.02, 95% CI 0.86 to 1.19 for AG; HR 1.11, 95% CI 0.91 to 1.37 for AA) in the overall cohort. Similar results were seen for the "A" allele for rs12149545. In the CABG subgroup, AG genotype for rs708272 was associated with an increased mortality (HR 1.38, 95% CI 1.06 to 1.79) compared with GG genotype. Results remained consistent using dominant model of inheritance. In conclusion, genetic CETP variants were not associated with recurrent MI or recurrent revascularization in overall cohort with a possible mortality increase in patients who underwent CABG., (Published by Elsevier Inc.)

Background: Ceruloplasmin (Cp) decreases nitric oxide bioavailability in blood and has been associated with cardiovascular disease (CVD) in clinical studies. We assessed the associations between Cp and incident heart failure (HF), death, and CVD in the Atherosclerosis Risk in Communities (ARIC) study., Methods and Results: Cp was measured at ARIC visit 4 (1996-1998). We studied 9240 individuals without HF or CVD at ARIC visit 4 and followed them for a mean of 10.5 years. Genome-wide association study was performed to identify genetic determinants of Cp levels and evaluate their association with incident HF in ARIC participants. Cp levels (mean±SD) were higher in women versus men (335±79 versus 258±44 mg/L; P<0.0001), women on versus not on hormone-replacement therapy (398±89 versus 291±60 mg/L; P<0.0001), and African Americans versus whites (299±63 versus 293±74 mg/L; P=0.0005). After adjusting for traditional risk factors, high-sensitivity C-reactive protein, N-terminal pro-B-type natriuretic peptide, and high-sensitivity cardiac troponin T, higher levels of Cp were associated with HF (hazard ratio, 1.44; 95% confidence interval, 1.13-1.83) and mortality (hazard ratio, 1.38; 95% confidence interval, 1.11-1.63). A locus on the ceruloplasmin gene on chromosome 3 was significantly associated with Cp levels (normal 295.56±77.60 mg/L; heterozygote 316.72±88.02 mg/L; homozygote 331.04±85.40 mg/L; P=8.3×10(-13)) but not with incident HF. After adjustment for traditional risk factors, Cp levels were also weekly associated with CVD., Conclusions: Cp was associated with incident HF, mortality, and CVD in the ARIC population. A single locus on chromosome 3 was associated with Cp levels but not with HF.

Background and Purpose: Increased levels of plasma troponins and natriuretic peptides are associated with increased risk of cardiovascular disease, but only limited information exists on these biomarkers and stroke occurrence. In a prospective epidemiological study, we tested the hypothesis that high-sensitivity troponin T (TnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are associated positively with incidence of stroke., Methods: The Atherosclerosis Risk in Communities (ARIC) Study measured plasma TnT and NT-proBNP in 10 902 men or women initially free of stroke and followed them for a mean of 11.3 years for stroke occurrence (n=507)., Results: Both biomarkers were associated positively with total stroke, nonlacunar ischemic, and especially cardioembolic stroke, but not with lacunar or hemorrhagic stroke. For example, after adjustment for prevalent risk factors and cardiac diseases, the hazard ratios (95% CIs) for jointly high values of TnT and NT-proBNP (versus neither biomarker high) were 2.70 (1.92-3.79) for total stroke and 6.26 (3.40-11.5) for cardioembolic stroke. Associations with stroke appeared somewhat stronger for NT-proBNP than TnT. Strikingly, ≈ 58% of cardioembolic strokes occurred in the highest quintile of prestroke NT-proBNP, and 32% of cardioembolic strokes occurred in participants who had both NT-proBNP in the highest quintile and were known by ARIC to have atrial fibrillation sometime before their cardioembolic stroke occurrence., Conclusions: In the general population, elevated plasma TnT and NT-proBNP concentrations are associated with increased risk of cardioembolic and other nonlacunar ischemic strokes.