bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 5690: Idiopathic Catecholamine-sensitive Epicardial Ventricular Tachycardia At The Crux Of The Heart
Authors: Doppalapudi Harish , Ramaswamy Karthik , Ahn Joon , Yamada Takumi , Kay G Neal
Published: July 2021

Idiopathic ventricular tachycardia (VT) has been described from the epicardial surface of the left ventricle (LV), usually near the summit of the LV in the outflow tract. Ablation of these VTs may be possible by delivery of energy within the coronary venous system or directly on the epicardial surface. We describe a distinct syndrome of focal epicardial VT induced by catecholamine infusion that arises from the crux of the heart. Among 340 cases of idiopathic VT referred for catheter ablation, 4 patients were identified with a clinical syndrome of catecholamine sensitive VT that was mapped to the epicardial surface at the crux of the heart. There were 3 males and 1 female (age 31–79 yrs, mean 58). VT was sustained in all patients and associated with syncope or near syncope in 3 of 4 pts. The LVEF was >0.55 in 3 pts and mildly depressed (0.45) in 1 pt. In all pts VT could be induced with programmed stimulation or burst pacing from the right ventricular apex but required the infusion of isoproterenol for induction in 3. The VT was very rapid with a mean cycle length of 264 msec. The surface ECG during VT demonstrated a left superior axis QRS morphology in all pts, with an abrupt precordial tansition from V1 to V2 in 3 pts and R waves across the precordium in one. The precordial maximal deflection index was > 0.55 in all pts (mean 0.67). The site of earliest activation during intracardiac mapping occurred at the crux of the heart with activation in the middle cardiac vein or proximal coronary sinus recorded 20 –50 msec (mean −38 msec) prior to the onset of the surface QRS. Catheter ablation with irrigated RF was attempted within the middle cardiac vein or proximal coronary sinus in all pts and was successful in 1. In 2 of 3 remaining pts, percutaneous epicardial RF ablation was attempted and was successful. Simultaneous coronary angiography demonstrated the site of earliest activation within 5–10 mm of the proximal posterior descending coronary artery (PDA). There was no acute narrowing of the PDA in any pt following ablation. Idiopathic VT may arise from the epicardial surface at the crux of the heart in close proximity to the PDA. This syndrome can result in very rapid, catecholamine sensitive VT, and may require careful attention to the PDA during ablation.
Abstract 5695: Arrhythmogenic Cardiac Death in Implantable Cardioverter Defibrillator Recipients: A Long-term Study of 783 Consecutive Patients
Authors: Duray Gabor Z , Schmitt Jörn , Goβ Stefanie , Berkhoff Panja , Khattar Patrick , Cicek-Hartvig Sule , Israel Carsten W , Hohnloser Stefan H
Published: July 2021

Introduction: Long-term mortality and cause of mortality of ICD recipients who are not enrolled in controlled clinical trials are not well known. This study seeked to determine cause-specific mortality in a large sample of unselected ICD recipients.

Methods: Consecutive ICD recipients followed at a tertiary referral center at regular 3-month intervals were included. In cases of missed visits, pts, their relatives and their family physicians were contacted. Based on all available evidence, causes of death were classified as cardiac arrhythmic (C–A), cardiac non-arrhythmic (C-NA), non cardial (non-C) and unknown.

Results: A total of 783 pts (primary prevention of sudden death in 252, secondary prevention in 531) were followed for 43 ± 30 months, during which time 193 pts died (24.7%, annual mortality 6.7%). Causes of death are shown in the figure

. Cox regression analysis revealed that all-cause morality was significantly affected by age (odds ratio 1.03, 95% confidence interval 1.01–1.05), LVEF (0.98, 0.96 – 0.99), NYHA > II (2.1, 1.35–3.26) at baseline, while ICD indication and development of electrical storm had no independent impact on all cause mortality. Predictors for arrhythmic mortality were LVEF (0.96, 0.91– 0.99), NYHA > II (5.3, 1.4 –19.6) spontaneous VT (9.9, 2.1– 45.2) or inducible VT (9.5, 2.0 – 44.2) as indication for ICD therapy.

Conclusion: In this unselected group of ICD recipients the mortality over 3.5 years was 25 %. Despite device therapy, at least 14% of patients died from presumably arrhythmic causes. Risk factors associated with arrhythmic mortality were a history of spontaneous or inducible monomorphic ventricular tachycardia, LVEF and higher NYHA class.
Abstract 5734: Left Ventricular Torsion Reflects Degree of Myocardial Fibrosis in Hypertrophic Cardiomyopathy
Authors: Nakaboh Ayumi , Goda Akiko , Nakao Shinji , Oka Katsumi , Tsujino Takeshi , Yuba Masao , Otsuka Misato , Matsumoto Mika , Yoshida Chikako , Naito Yoshiro , Lee-Kawabata Masaaki , Masuyama Tohru
Published: July 2021

Background
: LV torsion (LVtor) is reduced in patients with impaired LV systolic function, e.g., dilated cardiomyophaty. It used to be thought that LVtor is reduced in patients with hypertrophic caridiomyopathy (HCM) because of the myocardial disarray; however, recent observation showed that LVtor assessed with tagged magnetic resonance imaging (MRI) even increased in patients with HCM. Recently LVtor is assessable with novel ultrasound speckle tracking imaging (STI) method. This technique may be used to assess intra-ventricular torsion in the LV muscle (intra-LVtor) that occurs due to the different fiber directions between the endocardium and epicardium. In this study, we analyzed LVtor and intra-LVtor in light of LV fibrosis in patients with HCM.

Methods
: MRI and echo studies were performed in 10 patients with HCM in whom any medication had not been given to HCM. MRI was used to determine LV mass index. In addition, %DEmass was determined as an MRI index of the extent of myocardial fibrosis by dividing the extent of late gadolinium enhancement by LV mass. We acquired basal and apical short-axis LV images with 2D echocardiography for off-line STI analysis to determine LVtor and intra-LVtor. We traced 18 points of the endcardium and epicardium, respectively, and averaged all regional rotation at the basal and apical plane, respectively. LVtor was defined as the difference of LV rotation between the basal and apical plane. Intra-LVtor was defined as the difference in the rotation between the endcardium and epicardium.

Results
:

There was a significant correlation between %DEmass and LVtor(r=−0.72, p<0.05, indicating that LVtor is reduced in HCM patients with larger extent of LV myocardial fibrosis.

There was no significant correlation between LVtor and LV mass index (r=−0.15, p=n.s.).

%DEmass also correlated with intra-LVtor (r=−0.67, p<0.05, indicating that intra-LVtor is reduced in HCM patients with larger extent of LV myocardial fibrosis.

Conclusions
: Both LV torsion and intra-LV torsion are reduced in HCM patients with extended LV fibrosis. In other words, the extent of myocardial fibrosis may be assessed with LVtor and intra-LVtor by use of speckle tracking imaging in patients with HCM.
Abstract 5754: Cardiac CT Angiography vs. SPECT Perfusion Imaging for the Evaluation of Patients with Acute Chest Pain
Authors: Rogers Ian S , Moloo Jamaluddin , Chae Claudia U , Blankstein Ron , Bamberg Fabian , Pena Antonio J , Seneviratne Sujith K , Truong Quynh A , Nichols John H , Ferencik Maros , Brown David F , Nagurney John T , Brady Thomas J , Hoffmann Udo
Published: July 2021

BACKGROUND: Over 5 million individuals present to EDs with acute chest pain each year, many of which are hospitalized for serial EKGs and cardiac enzymes followed by stress SPECT imaging. A potential alternative to SPECT is cardiac CT, which provides for the immediate and direct evaluation of coronary artery patency. We sought to determine the concordance between these modalities and the ability of CT to exclude ischemia in patients presenting with acute chest pain.

METHODS: We enrolled 368 subjects without a history of hemodynamically significant CAD who presented to the ED with acute chest pain yet had negative initial EKGs and cardiac enzymes. All subjects underwent 64-slice cardiac CTA, the results of which were blinded to caregivers, then were admitted for standard care including diagnostic testing, as deemed clinically warranted by the caregivers. CTA exams were scored as being diagnostically positive or negative for significant stenosis (>50% luminal narrowing) or as non-diagnostic. SPECT exams were scored as diagnostically pos or neg for ischemia or scar or as non-diagnostic (e.g., secondary to submaximal workload or artifact).

RESULTS: 151 of the 368 subjects (54±11 yrs, 56% men) had an exercise (n=109), adenosine (n=41), or dobutamine (n=1) SPECT exam as part of their clinical care. 115 (76%) of the SPECT exams were read as diagnostic (7 pos for ischemia, 2 pos for scar, and 106 neg), while 36 (24%) were non-diagnostic. In contrast, 135 of the 151 (89%) of the CT exams were read as diagnostic (17 pos, 118 neg), while only 16 (11%) were non-diagnostic (p <0.001). Among the 105 patients that had both diagnostic CT and SPECT exams, there was agreement between the modalities in 97/105 (92%) of patients. With SPECT defined as the standard for detecting ischemia, absence of significant stenosis on a diagnostic CT had a 98% NPV for excluding ischemia.

CONCLUSION: Cardiac CT appears to be as feasible as SPECT imaging in patients with acute chest pain but inconclusive initial ED evaluation and may have a lower rate of non-diagnostic exams. Consistent with the known high NPV of CCT, absence of significant stenosis on cardiac CT predicted the absence of SPECT based ischemia in 98% of subjects. Thus, cardiac CT may be sufficient to exclude ischemia in patients with acute chest pain.
Abstract 5763: Dynamic Contrast-Enhanced MRI Detects Early Plaque Progression in a Rabbit Model of Atherosclerosis
Authors: Kerwin William S , Ricks Jerry , Rosenfeld Michael
Published: July 2021

Recent studies have used dynamic contrast-enhanced (DCE) MRI to quantify the rate of uptake of gadolinium contrast agents in atherosclerotic plaque. The transfer constant
K

trans

, that quantifies the blood supply and permeability of the plaque, shows strong association with plaque inflammation. The purpose of this study was to explore the link between
K

trans

and plaque inflammation in a model of early atherosclerotic lesion development. Twelve NZW rabbits were placed on a 0.2% cholesterol diet and underwent balloon injury of the descending aorta. After 12 weeks, all rabbits underwent a DCE-MRI exam, after which 6 were euthanized and perfusion fixed to harvest the atherosclerotic aortas. The remaining 6 were imaged again at 24 weeks and their aortas were harvested. The DCE-MRI procedure utilized a unique, high-speed, small field-of-view imaging technique with quadruple inversion recovery blood suppression (turbo spin echo, TR=800 ms, TE=9ms, 3mm slice thickness, 0.5mm in-plane resolution). This allowed us to observe enhancement of the vessel wall without contamination from enhancement of the adjacent lumen. The DCE-MRI results were analyzed to determine the average, relative
K

trans

in the vessel wall and compared to histological assessments of the aortas.
K

trans

was significantly higher at 6 months compared to 3 months within the same animals (p<0.005) and compared to those euthanized at 3 months (p<0.001). No difference was observed between the two groups at 3 months (p=0.4). Histologically, aorta cross sections at 6 months had lesions that were no thicker than those at 3 months (0.49 vs. 0.45mm, p=0.6), but complex lesion features including necrotic cores, intraplaque hemorrhage, neovessels, and deep clusters of macrophages were significantly more common at 6 months (82% vs. 18%, p<0.001). The transformation of the lesions from simple to complex morphologies from 12 weeks to 24 coincided with a significant rise in
K

trans

. We attribute this rise to the development of neovessels in response to pro-inflammatory stimuli. We conclude that
K

trans

can be used to probe lesion characteristics and complexity in early atherosclerosis, with applications in early diagnosis and treatment monitoring.

This research has received full or partial funding support from the American Heart Association, AHA Pacific/Mountain Affiliate (Alaska, Arizona, Colorado, Hawaii, Idaho, Montana, Oregon, Washington & Wyoming).
Abstract 003: Change in Cardiovascular Risk Factors Associated with Weight Gain in the Dallas Heart Study
Authors: Powell Tiffany M , Ayers Colby R , de Lemos James A , Khera Amit , Lakoski Susan G , McGuire Darren K , Ballard-Barbash Rachel , Das Sandeep R
Published: July 2021

Background:
Concerning trends in weight gain from 2000-2009 exist in the Dallas Heart Study (DHS), a probability-based sample of Dallas County residents aged 30-65. However, the impact of significant weight gain (≥ 5% increase in body weight) on cardiovascular risk factors (CVRF) in this contemporary, multi-ethnic population is not known.

Methods:
We measured weight, LDL-c, blood pressure (SBP and DBP), and fasting glucose (FG) in 2,022 DHS participants (58% female) at study entry in 2000 and in 2009. Using logistic regression stratified by sex and race/ethnicity, we determined the age-adjusted odds of worsening CVRF (any increase in LDL-c, SBP, DBP or FG) for people who gained significant weight compared to those who did not.

Results:
Among women, 43% (N=500) gained significant weight, compared to 42% of men (N=355). Despite similar average weight gain (9.7±5.8 kg for women vs. 10±5.6 kg for men, p=0.4), women who gained significant weight had almost twice as large an increase in LDL-c (14±34 vs. 8±39 mg/dl, p=0.01) and SBP (12±18 vs. 6±19 mmHg, p<0.001) compared with men who gained significant weight. Increases in DBP (5±10 vs. 4±11 mmHg, p=0.05) and FG (4±29 vs. 2±32 mg/dl, p=0.30) were not significantly different between men and women. Among those with significant weight gain who were not on medications, SBP and LDL-c increases were higher in women compared with men (p<0.05). Differences in the amount of weight gained stratified by race and sex were modest (Table). Black women who gained significant weight were likely to have a worsening of all CVRF, while Hispanic women had the highest likelihood of having an increase in SBP associated with weight gain. In contrast, significant weight gain among men was not associated with worsening CVRF.

Conclusions:
Significant weight gain was associated with a deleterious impact on CVRF among women but not men. Disparate effects of weight gain between men and women highlight the importance of targeting aggressive weight control interventions toward women to help prevent adverse cardiac outcomes.
Abstract 009: Plain Water and Total Beverage Intakes and Risk of Type 2 Diabetes in Young and Middle-aged Women
Authors: Pan An , Malik Vasanti , Willett Walter C , Hu Frank B
Published: July 2021

Introduction:
Some caloric beverages (e.g., sugar-sweetened beverage and fruit juice) have been associated with an elevated risk of type 2 diabetes; therefore, substitution of these caloric beverages with non-caloric beverages such as plain water may be important for diabetes prevention. Few previous studies have examined the association between plain water or total beverage intake and risk of type 2 diabetes.

Methods:
We followed 82,900 women, aged 27-45 years and free of diabetes, cardiovascular disease and cancer at baseline, from 1991 to 2007. Diet, including various beverages, was assessed by food frequency questionnaires and updated every four years. Incident type 2 diabetes cases were confirmed by supplementary questionnaires. Cox proportional hazard models were used to calculate relative risks (RRs) and corresponding 95% confidence intervals (CIs), and we estimated the effect of “substituting” a serving of one beverage for another by including both as continuous variables in the same multivariable model. The difference in their beta coefficients and their variances and covariance were used to estimate the RR and 95% CI for the substitution effect.

Results:
During 1,294,196 person-years of follow-up, we documented 2,980 incident T2DM cases. After adjustment for age and body mass index, compared with the reference group (<1 glass/d), the relative risks (RRs) and 95% confidence intervals (CIs) of type 2 diabetes according to categories of plain water consumption were 0.91 (0.81-1.02) for 1 glass/d, 0.91 (0.82-1.01) for 2-3 glasses/d, 0.98 (0.87-1.11) for 4-5 glasses/d, and 1.02 (0.89-1.18) for 6 or more glasses/d (P-for-trend=0.51). Further adjustment for other diabetes risk factors did not substantially alter the RRs. We estimated that substituting one serving/d of plain water for one serving/d of sugar-sweetened beverage or fruit juice was associated with a 10% (95% CI, 6%-13%) and 13% (95% CI, 7%-18%) lower risk of type 2 diabetes, respectively. In this cohort, no association was found for total beverage intake and risk of type 2 diabetes: compared with women who drank less than 6 servings/d of total beverage, the RRs (95% CIs) were 0.97 (0.87-1.09), 0.98 (0.88-1.10), 1.01 (0.89-11.5), and 0.99 (0.86-1.14) for women drank 6-8, 8-10, 10-12, and ≥12 servings/d of total beverages (P-for-trend=0.83).

Conclusions:
Increasing consumption of water per se was not associated with risk of type 2 diabetes, but substituting plain water for sugar-sweetened beverage or fruit juice was associated with a significantly lower risk of type 2 diabetes.
Abstract 011: Sex Hormone-Binding Globulin (SHBG) and Risk of Clinical Diabetes in American Black, Hispanic, and Asian/Pacific Islander Postmenopausal Women.
Authors: Chen Brian H , Brennan Kathleen , Goto Atsushi , Song Yiqing , Aziz Najib , You Nai-chieh Y , Wellons Melissa F , Manson JoAnn E , White Donna L , Butch Anthony W , Liu Simin
Published: July 2021

BACKGROUND:
Recent prospective studies have shown a strong inverse association between sex hormone-binding globulin (SHBG) levels and risk of clinical diabetes in Whites. However, it remains unknown whether this relation extends to other racial/ethnic populations.

METHODS:
We evaluated the association between baseline levels of SHBG and risk of clinical diabetes in the Women’s Health Initiative Observational Study. Over a median follow-up of 5.9 years, 542 postmenopausal women developed clinical diabetes (338 Blacks, 128 Hispanics, 76 Asians) and were matched to 1,110 controls (707 Blacks, 249 Hispanics, 154 Asians). To complement our protein-level findings, we also genotyped 5
SHBG
polymorphisms. We performed Mendelian randomization analysis to assess the potential causal relation between SHBG levels and risk of clinical diabetes.

RESULTS:
Overall, higher levels of SHBG at baseline were associated with a significantly lower risk of clinical diabetes (Relative risk [RR]=0.24, 95% confidence interval [CI]=0.15-0.39 for highest versus lowest quartile of SHBG, adjusted for BMI and other known diabetes risk factors). The associations remained consistent across ethnic groups (p-for-heterogeneity=0.72): RR=0.29 (95%CI=0.16-0.54) for Blacks, RR=0.26 (95%CI=0.09-0.74) for Hispanics, and RR=0.32 (95%CI=0.06-1.73) for Asians, comparing highest to lowest quartiles of SHBG. In addition,
SHBG
polymorphisms affected diabetes risk proportional to serum SHBG levels. Mendelian randomization analysis confirmed the significant direct effect of SHBG on diabetes development (p=0.03).

CONCLUSIONS:
In this prospective cohort of postmenopausal women, we observed a robust, inverse relation between serum levels of SHBG and clinical diabetes risk in American Blacks, Hispanics, and Asian/Pacific Islanders. Genetic variants associated with SHBG levels demonstrated a similar relationship, providing support for a causal role of SHBG in the pathogenesis of type 2 diabetes.
Abstract 024: Trends in Anatomical Location and Case Fatality of Myocardial Infarction in Four US Communities, 1987–2008: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Newman Jonathan D , Shimbo Daichi , Baggett Chris , Liu Xiaoxi , Crow Richard , Loehr Laura R , Folsom Aaron R , Rosamond Wayne D
Published: July 2021

INTRODUCTION:
Although the incidence of and mortality following ST-segment elevation MI (STEMI) is decreasing, time-trends in STEMI infarct location and associated prognosis have not been examined in a population-based community study.

METHODS:
We determined 22-year trends in age-adjusted, gender-specific incident hospitalized STEMI and 28-day case fatality among 35–74 year old residents of four ARIC surveillance study communities. STEMI location was assessed by 12-lead electrocardiograms (ECG) from hospital records and was coded as anterior (V2-V5), inferior (II, III, AVF), lateral (I, AVL, V6 alone or with V2-V5) or multiple (2 or more regions) infarct locations using Minnesota coding. Case fatalities were confirmed with linkage to the National Death Index.

RESULTS:
From 1987 to 2008, there were an estimated 6,108 (fatal or non-fatal) hospitalized STEMIs, with an average annual decrease of −4.0% (95% CI, −4.7, −3.3) in men and −3.1% (95% CI −4.1, −2.1) in women. By infarct location, 37.2% of STEMIs were inferior; 32.8% anterior; 16.8% multiple territories; and 13.2% lateral. Annually, inferior STEMI decreased by −1.5% (95% CI −2.4, −0.6) while STEMI in multiple infarct regions increased by 2.9% (95% CI 1.9, 4.3), Figure. The 28-day case fatality for anterior, inferior and lateral STEMI decreased from 10.9% (95% CI 7.9, 13.9) to 5.1% (95% CI 3.0, 7.2),
P
< 0.01; from 6.1% (95% CI 4.5, 7.6) to 3.5% (95% CI 2.0, 5.0),
P
= 0.03; and from 14.8% (95% CI 8.6, 21.1) to 6.3% (95% CI 3.0, 9.6),
P
= 0.01, respectively. In contrast, no significant change in 28-day case fatality for STEMI in multiple infarct regions was observed.

CONCLUSION:
Between 1987 and 2008, significant heterogeneity by infarct location was observed for incident STEMI and in 28-day mortality after STEMI. In contrast to STEMI in other infarct locations, the proportion of STEMI involving multiple infarct territories increased over 22 years of surveillance, without improvement in 28-day mortality. These findings may have implications for STEMI surveillance and management.
Abstract 044: Trends in Race/Ethnic Disparities in Ideal Cardiovascular Health: NHANES 1999-2006
Authors: Allen Norrina B , Ning Hongyan , Lloyd-Jones Donald
Published: July 2021

Background:
Significant racial/ethnic disparities exist in the cardiovascular health of the nation. Prior studies have identified differences between groups, but have not summarized trends in these disparities across multiple race/ethnic subgroups, which could allow us to assess the extent to which we are achieving disparity-related goals.

Methods:
We used NHANES Surveys from cycles 1999–2000, 2001–2002, 2003–2004, and 2005–2006 to examine the age-adjusted prevalence of ideal levels of CV health factors by race/ethnicity. Ideal levels of BMI, cholesterol, glucose, blood pressure, diet, physical activity and smoking were defined according to the AHA 2020 strategic goals. Racial/ethnic groups were categorized as Hispanic, Non-Hispanic White, Non-Hispanic Black and other. Both absolute (Between Group Variance- BGV) and relative measures (Theil Index -T) of disparities were calculated, calculations were weighted by population share. The percentage change in disparities relative to 1999–2000 was examined.

Results:
Age-adjusted rates of ideal CV health components and the percentage change from 1999–2006 varied by race/ethnicity (see Table). Disparities in the prevalence rates of ideal levels of blood pressure, cholesterol and physical activity have increased dramatically between race/ethnic groups in both men and women (see Table). Disparities in smoking and diet have increased in men but decreased in women. Disparities in BMI have changed little in men (BGV= 0.5%, T=−37.8%), but increased dramatically in women (BGV= 894%, T=280%). Findings were generally similar for both absolute and relative measures of disparities.

Conclusions:
Representative national data on these summary measures of disparities suggest that disparities between race/ethnic groups have increased for many cardiovascular health factors over the past decade. Understanding the issues underlying these increasing disparities and addressing them will be critical to improving the cardiovascular health of all Americans by 2020 and beyond.
Abstract 046: Spatial Variation of Predictors of Hypertension in Sub-Saharan Africa: A Case Study of South-Africa
Authors: Kandala Ngianga-Bakwin , Tigbe William , Manda Samuel O , Stranges Saverio
Published: July 2021

Sub-Saharan Africa (SSA) is a region of striking socio-economic and demographic diversities, characterized by an ongoing epidemiologic transition. Recent work shows that hypertension is of public health importance in SSA, particularly in urban areas, with evidence of considerable under-diagnosis, poor management and lack of communitywide preventive strategies. Our objective was to examine the spatial variation of predictors of hypertension at the province-level in South Africa, after accounting for individual risk factors such socio-demographics, lifestyle, and chronic co-morbidities. Our analysis was based on the 1998 South African Health and Demographic Survey (HDS), including 13,827 men and women aged 15 and over. Individual data were collected on self-reported lifestyle habits and chronic co-morbidities, but were aggregated to the current 52 health districts and 9 provinces in the country. We used a Bayesian geo-additive mixed model based on Markov Chain Monte Carlo techniques to map the spatial distribution of hypertension at the province-level, accounting for individual risk factors. The overall prevalence of hypertension (blood pressure ≥140/90 mm Hg) was 25.1%. In multivariable Bayesian geo-additive regression analyses, men [odds ratio (OR) & 95% Credible Region (CR): 1.29 (1.14, 1.44)], coloured [1.20 (1.01, 1.42)], current smokers [1.14 (1.03, 1.27)] and current drinkers [1.14 (1.01, 1.27)] were consistently associated with higher prevalence of hypertension. In spatial analyses, a significantly higher prevalence of hypertension was found in provinces with higher poverty and income inequalities [Free State: 1.34 (1.14, 1.62); North West: 1.33 (1.12, 1.58)]. To our knowledge this was the first study, which attempted to estimate the spatial variation of predictors of hypertension at the province-level in South Africa, after accounting for individual risk factors. Findings suggest distinct spatial patterns in hypertension prevalence in South Africa, pointing to the independent role of socio-economic disparities at the province-level, beyond individual-level risk factors for hypertension in this setting.
Abstract 049: Promoter Methylation of Glucocorticoid Receptor Gene Is Associated with Subclinical Cardiovascular Disease: a Monozygotic Twin Study
Authors: Zhao Jinying , Goldberg Jack , Quyyumi Arshed A , Irina Uphoff , Vaccarino Viola
Published: July 2021

Background:
Epigenetic mechanisms are increasingly being recognized as a key factor in the pathogenesis of cardiovascular disease (CVD). Endothelial dysfunction assessed by brachial artery flow-mediated dilation (FMD) is a marker for early atherosclerotic CVD, a predictor of future cardiovascular events. The glucocorticoid receptor gene (NR3C1) regulates a variety of biological processes including cardiovascular, metabolic, immunologic, and homeostatic functions. Genetic polymorphisms in NR3C1 have been associated with atherosclerosis and several cardiometabolic risk factors. However, no study has yet investigated the potential role of NR3C1 promoter methylation in atherosclerosis. Objective: To examine the potential association between NR3C1 promoter methylation and FMD in a monozygotic (MZ) twin sample.

Method:
We studied 84 male-male monozygotic twin pairs drawn from the Vietnam Era Twin Registry. These twin pairs were recruited by the Emory Twins Heart Study, which investigates psychological, behavioral and biological risk factors for subclinical cardiovascular disease using a twin design. The twins were free of a self-reported previous diagnosis of cardiovascular disease at the time of enrollment. Brachial artery FMD was measured by ultrasound. The methylation levels of 25 CpG residues in the NR3C1 promoter region in peripheral blood leukocytes was quantified by bisulfite pyrosequencing. The association between DNA methylation variation and FMD was examined using nonparametric regression by regressing the intra-pair difference in FMD on the intra-pair difference in DNA methylation level at each CpG site, separately, adjusting for potential confounders including age, smoking, body mass index (BMI), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), blood glucose level and systolic blood pressure. Multiple testing was controlled by the false discovery rate.

Results:
Mean methylation level of the 25 CpG sites encompassing the NR3C1 promoter region was 2.1%. Methylation levels at 7 of the 25 CpG residues were significantly associated with FMD. On average, a 10% increase in mean methylation was associated with a 0.13 increase in FMD (95% CI: 0.09–0.17; p <0.0001) after controlling for confounding factors.

Conclusion:
Increased promoter methylation of NR3C1 is significantly associated with decreased risk for subclinical atherosclerosis assessed by FMD. Given the critical role of this gene in regulating hypothalamic-pituitary-adrenal axis (HPA) function, it is possible that aberrant promoter methylation of this gene may affect atherogenesis through its influence on the HPA system, a mechanism known to be involved in cardiovascular disease.
Abstract 052: Short-acting Hypnotic Drugs Increase Mortality and Obese Patients are Particularly Vulnerable
Authors: Langer Robert D , Kripke Daniel F , Kline Lawrence E
Published: July 2021

Background:
An estimated 6% – 10% of U.S. adults took a hypnotic drug for poor sleep in 2010. At least 18 studies have reported significant (p<0.05) associations of hypnotic usage with increased mortality. However, most lacked data on newer, supposedly safer, short-acting drugs, and had limited control for confounding by health status. Furthermore, little is known regarding potentially heightened risks in specific vulnerable populations.

Objective:
The present study was designed to test whether newer short-acting hypnotic drugs were associated with increased mortality after controlling for comorbid conditions, and to assess risks within subgroups of patients with specific medical conditions.

Methods:
Using electronic medical records from a large U.S. health system the authors conducted a one-to-two matched-cohort survival analysis of associations between hypnotic drug use and mortality. Records were extracted for 10,529 hypnotic users and 23,676 matched controls with no hypnotic prescriptions, mean age 54 years, followed for an average of 2.5 years between 2002 and 2006. Hazard ratios (HR) for death were computed from Cox models controlled for risk factors and stratified on comorbidites.

Results:
The short-acting drugs zolpidem (41%) and temazapam (20%) accounted for the majority of use. Patients prescribed any hypnotic had substantially elevated hazards of dying compared to non-users. Importantly, the death hazard was evident even in the lowest tertile, 1 to 18 pills per year, HR 3.60 (95% Confidence Interval, 2.92 – 4.44). HRs for the remaining tertiles were 4.43 (3.67 – 5.36) and 5.32 (4.50 – 6.30), demonstrating a dose-response association. HR were robust within subgroups restricted to users and non-users with identical comorbidity, implying that selective use of hypnotics by patients in poor health was an unlikely explanation for the excess mortality. Obesity emerged as a marker of increased vulnerability. Among 2206 patients with a diagnosis of obesity, (mean BMI 38.8), the mortality HRs by hypnotic tertile were 8.07 (3.64 – 17.89), 6.37 (2.73 – 14.88), and 9.34 (4.47 – 19.52). Additional models were fitted for patients with the combination of Obesity + Diabetes + Hypertension to evaluate the possibility that this risk was driven by metabolic syndrome. HRs for that combination were slightly lower than those for obesity alone, suggesting that obesity was the primary factor.

Conclusions:
Short-acting hypnotics were associated with a more than 3-fold increased hazard of death that, even at low levels of use. Obese patients appear particularly vulnerable, perhaps through interaction with sleep apnea. Emerging evidence for substantial harm, even with limited exposure to hypnotics, should be weighed against any benefits.
Abstract 054: The Use of Administrative Data and Natural Language Processing to Estimate the Incidence of Statin-related Rhabdomyolysis
Authors: Floyd James S , Heckbert Susan R , Weiss Noel S , Carrell David S , Psaty Bruce M
Published: July 2021

Introduction:
Despite the problem of misclassification, many studies of adverse drug reactions (ADRs) rely on administrative data rather than events validated by medical record review. Hypothesis: We evaluated the new ICD-9 code for rhabdomyolysis (728.88) and natural language processing (NLP) as methods to identify cases of statin-related rhabdomyolysis, and estimated the incidence with various statins and doses.

Methods:
We conducted a population-based study of statin users in a health maintenance organization in Washington State from 2006-2010. Trained abstractors reviewed the medical records of selected statin users to identify cases of statin-related rhabdomyolysis and myopathy, defined as muscle injury with a peak creatine kinase level ≥ 10x and 5-10x the upper limit of normal, in the absence of other likely etiologies.

Results:
The review of medical records for 361 statin users with an administrative code for rhabdomyolysis or related codes yielded 24 cases of statin-related rhabdomyolysis and 12 of myopathy. NLP methods identified another 5 cases of rhabdomyolysis and 6 of myopathy. The positive predictive value of the rhabdomyolysis ICD-9 code in statin users was only 7.5%. Incidence rates appear in the
Table
. The incidence rate ratio (IRR) of statin-related rhabdomyolysis for simvastatin compared with other statins was 2.61 (95% CI, 1.03-7.84), and the IRR for the 80mg dose of simvastatin compared with 20mg was 12.2 (95% CI, 3.6-52.3). In an analysis of administrative diagnostic data alone, the IRR for simvastatin compared with other statins was 1.03 (95% CI 0.80-1.34), and for 80 mg dose of simvastatin compared with 20 mg it was 1.77 (95% CI 1.05-2.88).

Conclusions:
Use of the administrative diagnostic code for rhabdomyolysis was highly nonspecific for this ADR and resulted in weaker associations than methods that verified ADRs with medical record review. These findings raise questions about the use of administrative data alone in studies of other medication ADRs when those events have other possible etiologies.

Incidence rates for statin-related rhabdomyolysis and myopathy.

Cases

Incidence rates (95% CI)
*

Statin
Person-years of exposure
Statin-related rhabdomyolysis
Statin-related myopathy
Statin-related rhabdomyolysis
Statin-related myopathy

Simvastatin
170,605
23
10
13.2 (8.6-20.2)
5.9 (2.8-10.8)

<20mg/day
21,832
0
0
0 (0-16.9)
0 (0-16.9)

20-39mg/day
75,082
4
2
5.3 (1.5-13.6)
2.7 (0.3-9.6)

40-79mg/day
56,703
8
4
14.1 (6.1-27.8)
7.1 (1.9-18.1)

≥80mg/day
16,876
11
4
64.8 (32.3-116.9)
23.6 (6.4-60.3)

Other statins
116,154
6
8
5.2 (1.9-11.2)
6.9 (3.0-13.6)

All statins
286,758
29
18
10.1 (7.8-14.5)
6.3 (3.7-9.9)

*

Cases per 100,000 person-years of statin use
Abstract 059: Long-term Exposure to Oxides of Nitrogen and Left Ventricular Mass in the Multi-Ethnic Study of Atherosclerosis and Air Pollution
Authors: Van Hee Victor C , Oron Assaf P , Bluemke David A , Szpiro Adam A , Diez-Roux Ana V , Siscovick David , Kaufman Joel D
Published: July 2021

Objective:
To determine whether long-term exposure to oxides of nitrogen (NO
x
) is associated with left ventricular mass index (LVMI) in adults without known cardiovascular disease (CVD).

Background:
An association between very close (<50 meter) residential proximity to major roadways and LVMI, an important predictor of heart failure, has been previously described. To date, the relationship between LVMI and NO
x
, a specific, gaseous traffic related pollutant and more reliable surrogate for traffic-related pollution, has not been examined.

Methods:
This study included 4125 participants free of clinical cardiovascular disease in the Multi-Ethnic Study of Atherosclerosis (MESA) who underwent cardiac MRI, cardiac computed tomography (CT), and an extensive air pollution exposure assessment campaign to determine long-term individual residential exposure to NO
x
. This study used year 2000 average exposure to estimate long term exposure to NO
x
. LVMI was calculated by indexing cardiac MRI measures of left ventricular mass to body surface area measured at the exam. Agatston score was calculated based on cardiac CT. Multiple linear regression was used to examine the association between long-term exposure to NO
x
and LVMI, adjusted for multiple potential confounders including study site. To examine whether such relationships may be mediated by atherosclerosis or blood pressure, additional adjustment for Agatston score and blood pressure was performed.

Results:
An interquartile range (44 ppb) increase in estimated residential NO
x
was associated with significantly higher LVMI (1.6 g/m
2
, 95% CI: 0.1 to 3.1, p=0.03). Such estimates were comparable to prior associations observed for the relationship between close residential proximity to major roadways and LVMI (comparing individuals living 150m away). Additional adjustment for Agatston score and blood pressure had no effect on estimates of association. Stratified analyses suggested interactions with age, with younger individuals demonstrating larger associations than older individuals (p for interaction = 0.05). No significant evidence of effect modification by race, gender, other cardiovascular risk factors, or study site was observed.

Conclusions:
This study further supports the observation that long-term exposure to traffic-related air pollution is associated with higher left ventricular mass, and suggests that such associations may be independent of effects on blood pressure or atherosclerotic disease.
Abstract 060: Contribution of Immunodeficiency to Coronary Heart Disease: Cohort Study of HIV-infected and HIV-uninfected Kaiser Permanente Members
Authors: Klein Daniel B , Leyden Wendy A , Xu Lanfang , Chao Chun R , Horberg Michael A , Towner William J , Hurley Leo B , Quesenberry Charles P , Silverberg Michael J
Published: July 2021

Background:
We compared CHD rates among HIV+ and HIV- patients in a large integrated care system, to explore the role of immunodeficiency in CHD.

Methods:
Kaiser Permanente (KP) California serves >6 million members. Using previously described databases, we matched adult HIV+ members to HIV- members (1:10 ratio) on age, sex, medical center and year of start of follow-up. We searched hospitalization records to identify members with discharge diagnoses codes [MH1] ICD-9: 410x-411x, 413x-414x. The cohort was followed from first KP enrollment after 1996 until earliest recorded CHD event, death, KP disenrollment, or 12/31/2009. We stratified HIV+ members by antiretroviral therapy (ART) use, recent and lowest KP-recorded CD4, and compared rates with HIV- KP members. We obtained rate ratios (RRs) for any CHD diagnosis and MIs from Poisson regression models adjusting for age, sex, race, tobacco use, alcohol/drug abuse, obesity, diabetes, use of lipid lowering, and hypertension therapy. An additional analysis of only HIV+ individuals examined the effects of antiretroviral therapy use, recent HIV RNA, and recent and nadir CD4 on CHD.[MH2]

Results:
22,081 HIV+ and 215,158 HIV- members contributed 101,044 pys and 1,265,819 pys respectively. HIV+ had 446 CHD events (including 280 MIs), corresponding to a rate of 451/100,000 py. HIV- had 3,926 CHD events (including 2,064 MIs), corresponding to a rate of 316 cases/100,000 py. The adjusted CHD RR for HIV status was 1.4 (95% CI: 1.3-1.6; p<0.001), and the adjusted MI RR was 1.7 (95% CI: 1.5-1.9; p<0.001). CHD RRs for HIV+ as stratified by ART use and CD4 level are shown in
Table
(with HIV- as reference).

Table.

Adjusted rate ratios
*
for CHD among HIV+ individuals by recent and lowest CD4

Recent CD4
Lowest KP CD4

RR
(95% CI)
p value
RR
(95% CI)
p value

ART+, CD4 ≥500
0.9
(0.7, 1.1)
0.218
0.8
(0.5, 1.2)
0.231

ART+, CD4 201-499
1.4
(1.2, 1.6)
<0.001
1.1
(0.9, 1.3)
0.300

ART+, CD4 ≤200
1.8
(1.4, 2.2)
<0.001
1.4
(1.3, 1.6)
<0.001

ART-, CD4 ≥500
1.3
(0.9, 1.9)
0.213
1.3
(0.8, 2.1)
0.363

ART-, CD4 201-499
1.1
(0.7, 1.7)
0.671
1.3
(0.9, 1.8)
0.182

ART-, CD4 ≤200
1.8
(0.9, 3.8)
0.113
1.1
(0.6, 2.2)
0.778

*

HIV- as reference for all RRs

Conclusions:
Adjusting for traditional risk factors, HIV+ individuals have a statistically significant increased risk for cardiovascular complications. Aggressive attention to modifiable risk factors is particularly important. As increased CHD risk was not seen for patients with relatively preserved CD4, earlier initiation of ART may further reduce CHD [. l
Abstract 061: Long-chain monounsaturated fatty acids and congestive heart failure incidence: the Atherosclerosis Risk in Communities Study
Authors: Imamura Fumiaki , Lemaitre Rozenn N , Steffen Lyn M , Folsom Aaron R , Siscovick David S , Mozaffarian Dariush
Published: July 2021

Background:
Animal experiments in 1970s demonstrated direct cardiotoxicity of long-chain monounsaturated fatty acid (LCMUFA, 22:1 and 24:1 fatty acids) consumption. We recently found plasma phospholipid 22:1 and 24:1 to be associated with 34% and 75% higher risk (quintiles 5 vs. 1), respectively, of congestive heart failure (CHF) among older adults in the Cardiovascular Health Study. We wished to validate these results in a second independent cohort of middle-aged adults.

Methods:
We evaluated 3,577 adults free of CHF at baseline (age=54.1±5.8) in the Minnesota subcohort of the Atherosclerosis Risk in Communities Study (ARIC) in whom plasma phospholipid LCMUFA were measured. Incident CHF was ascertained from 1988 to 2008 by annual phone contacts, hospitalization discharge codes, and death certificates. Using multivariate Cox models, we evaluated prospective association of each LCMUFA with incident CHF, and potential mediation via CHF risk factors, including ECG left ventricular hypertrophy, and incident coronary heart disease (CHD). As a negative control, we also evaluated incident stroke, given its many shared risk factors for CHF but no link to potentially direct cardiotoxicity.

Results:
Mean±SD plasma phospholipid levels (% of total fatty acids) of 22:1 and 24:1 were 0.01±0.03 and 0.58±0.17. Over the 64,438 person-years of follow-up, 330 CHF events occurred. After multivariable adjustment, higher levels of 22:1 and 24:1 were associated with higher risk of CHF (Figure). Hazard ratios (95%CI) for quintiles 5 vs. 1 of 22:1 and 24:1 levels were 1.57 (1.11–2.23) and 1.92 (1.22–3.03) (p trend=0.03 and 0.002), respectively. These associations were only partly attenuated by potential mediators, including incident CHD. Neither LCMUFA was associated with incident stroke (not shown).

Conclusions:
Higher 22:1 and 24:1 LCMUFA levels were associated with CHF risk in middle-aged adults, consistent with our prior findings in older adults. These findings support the possibility of clinical cardiotoxicity of LCMUFA in humans.
Abstract MP002: Dietary Intake of Marine Omega-3 Fatty Acids is Directly Associated with Coronary Flow Reserve among Male Middle-Aged Twins
Authors: Eufinger Silvia C , Vaccarino Viola
Published: July 2021

Introduction:
Evidence from previous studies suggests that dietary marine omega-3 fatty acids have cardioprotective properties. However, our understanding of the mechanism for these beneficial effects remains limited. We sought to examine the association between marine omega-3 fatty acid intake and coronary flow reserve (CFR), a measure of overall coronary vasodilator capacity and microvascular function.

Hypothesis:
Increased dietary intake of marine omega-3 fatty acids is associated with higher CFR.

Methods:
A sample of 259 male middle-aged twins, including 115 monozygotic and dizygotic twin pairs and 29 unpaired twins, with no previous history of coronary heart disease (CHD), was recruited from the Vietnam Era Twin Registry. Prior to the study visit, all twins completed a 3-day food record detailing their diet for the previous three days. Dietary information was analyzed using specialized nutrition software and reported intakes of various types of fish were used to derive marine omega-3 fatty acid (docosahexaenoic acid [DHA] and eicosapentaenoic acid [EPA]) intake. CFR was measured using positron emission tomography [N
13
] ammonia with quantitation of myocardial blood flow at rest and after adenosine stress. Mixed-effect regression analysis was used to assess the association between marine omega-3 fatty acid intake and CFR both at the individual level and within twin pairs. Potential confounders included demographic characteristics, lifestyle factors (including physical activity), traditional cardiovascular disease (CVD) risk factors, use of omega-3 and multivitamin supplements, total energy intake, and other nutritional factors such as intake of cholesterol, sodium, alcohol, sugar-sweetened beverages, and saturated and monounsaturated fatty acids.

Results:
The twins’ mean age was 54 years (SD = 3.0) and 93.1% (241 out of 259) were white. An increase in dietary intake of marine omega-3 fatty acids of 1 g/d was associated with a 7.6% higher CFR (95% CI: 0.6, 15.2) after adjustment for potential confounders (
P
= 0.033). This association also persisted within twin pairs: a 1 g/d within-pair difference in dietary intake of marine omega-3 fatty acids was associated with a 16.3% higher CFR in the twin with the greater dietary intake of marine omega-3 fatty acids than in the co-twin with the lower dietary intake (
P
= 0.020). These associations did not differ by zygosity.

Conclusions:
Dietary intake of marine omega-3 fatty acids is directly associated with CFR, a measure of coronary microvascular function, independent of traditional CVD risk factors and shared familial and genetic factors. Our study suggests a potential novel mechanism for the protective effects of dietary marine omega-3 fatty acids on the cardiovascular system and supports the benefit of consuming marine omega-3 fatty acids to promote cardiovascular health.