bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 3636: Ekg Left Ventricular Hypertrophy And Cardiovascular Events In Patients With Type 1 And Type 2 Diabetes Mellitus
Authors: Salvetti Massimo , Muiesan Maria Lorenza , Stanga Barbara , Cimino Antonio , Valentini Umberto , Paini Anna , Belotti Eugenia , Micheletti Linda , Aggiusti Carlo , Rosei Claudia Agabiti , Paderno Valentina , Rosei Enrico Agabiti
Published: July 2021

Background:
A large number of studies have demonstrated that LVH detected with standard electrocardiography is an independent predictor of future cardiovascular complications in various subsets of patients. Despite the fact that ECG represents the first cardiovascular test performed in diabetics, few data are available on the prognostic significance of EKG LVH in these patients.

Aim of this study
was to evaluate the relationship between EKG LVH and the risk of future cardiovascular events in a wide group of patients with diabetes mellitus (DM).

Methods
A total of 1131 prospectively identified patients with type 1 (n=613, age 36 ± 13 years, 40 % women, BP 127 ± 16/79 ± 8 mmHg, total cholesterol 196 ± 43 mg/dl, HbA1C 7.81 ± 1.67%) and with type 2 DM (n=618, age 53 ± 11 years, 34 % women, BP 137 ± 18/82 ± 8 mmHg, total cholesterol 208 ± 41 mg/dl, HbA1C 7.97 ± 1.72%) were studied. At baseline all subjects underwent baseline clinical examination with blood pressure measurement according to current guidelines, standard laboratory examinations and a 12 leads electrocardiogram. LVH was defined as the presence of a “Sokolow-Lyon” voltage >38 mm and/or a “Cornell voltage QRS duration product” >2440 mm* msec. Treatment was not standardized.

Results
LVH prevalence was 8.3 % in type 2 DM and 6.4 % in type 1 DM. Patients were followed for 63 ± 27 months (range 1–126). A first non fatal cardiovascular event occurred in 62 patients. Kaplan-Meyer analysis revealed a higher risk of cardiovascular events in patients with LVH both with type 1 and type 2 DM (Log Rank Mantel Cox p<0.01). In Cox analysis, controlling for age, gender, BMI, history of cardiovascular disease, systolic blood pressure, heart rate, total plasma cholesterol, HbA1c, albuminuria and antihypertensive treatment, the presence of LVH was associated with an increased risk of cardiovascular events in all patients (odds ratio 2.96, 95% CI 1.39 to 6.32, p<0.01) and separately in DM type 1 (odds ratio 5.71, 95% CI 1.29 to 25.17, p=0.02) and in type 2 DM (odds ratio 2.92, 95% CI 1.02 to 8.35, p=0.05).

Conclusions:
Our data demonstrate that in patients with DM the detection of LVH by EKG is associated to an increased risk of cardiovascular events, independently of other risk factors and represent the first demonstration of the prognostic significance of EKG-LVH in patients with type 1 diabetes
Abstract 3638: Abnormalities of Left Ventricular Geometry in Youth with Type 2 Diabetes: A greater effect of obesity than fasting glucose
Authors: Ippisch Holly M , Daniels Stephen R , Urbina Elaine M , Dolan Lawrence M , Wang Baiyang , Kimball Thomas R
Published: July 2021

Background:
Type 2 diabetes (T2), previously a disease of adult onset, is increasing in prevalence amongst children and young adults. Yet the presence of cardiovascular risks, such as left ventricular hypertrophy (LVH) are largely unknown in this population.

Purpose:
To determine the frequencies of abnormal left ventricular (LV) mass and geometry in young people with T2.

Methods:
LV mass (LVM) was assessed by echo, indexed to height in meters 2.7, and compared to healthy Obese (O) and Lean (L) controls of similar age, gender matched, non-diabetics. Statistical analysis was performed with non-parametric tests. Data are presented as mean and standard deviations.

Results:
A total of 98 T2 (ages 11–23 yrs, 19 ± 4 yrs; 64% female, 36% male; BMI 35 ± 8) were evaluated and compared to O & L controls (BMI 36 ± 7 and 21 ± 3, respectively). Although indexed LVM was higher for T2 compared to L (36 ± 11 vs. 27 ± 6 gm/m2.7, p = <0.0001) it was not different compared to O controls. LV geometry was similarly abnormal in the T2 & O groups, with increased frequency of concentric and eccentric LVH compared to lean controls (Table 1

). Systolic (SBP) and diastolic (DBP) blood pressure were higher in the T2 vs. O & L (p<0.05). In univariate analysis for T2, indexed LVM correlated with BMI (p<0.0001, R=0.65) but not: BP, gender, race, or fasting plasma glucose. In multiple regression for T2, log index LVM was predicted by BMI (p<0.0001) & gender (p=0.02) (R2=0.46) but not BP, race or fasting plasma glucose.

Conclusions:
Young people with T2 have higher indexed LVM and abnormal LV geometry compared to lean controls. Obesity, not fasting plasma glucose seems to be a primary factor associated with LVM. These data suggest that obesity is a primary factor in the early cardiac changes in youth with T2. Early weight loss may have a greater beneficial effect on cardiac geometry than glycemic control.

Table I:

Prevalence of Left Ventricular Geometries
Abstract 3654: Inflammation Factors, Coronary Calcium and Risk of Cardiovascular Events: The Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Cushman Mary , McClelland Robyn , Folsom Aaron , Pamela Ouyang , Blumenthal Roger , Detrano Robert , Post Wendy , Goff David , Barr Graham , Liu Kiang , Tracy Russell
Published: July 2021

Background
. Inflammation factors and coronary calcium score are associated with risk of CVD events. There are few studies including large numbers of participants from minority ethnic groups.

Methods.
From 2000 –2002, 6,814 men and women without CVD were enrolled; white, black, Hispanic and Chinese; aged 45– 84, free of CVD. We measured C-reactive protein (CRP), interleukin-6 (IL-6), fibrinogen and computed tomography for coronary artery calcium (CAC) scoring. Over 3.5 years follow up there were 238 first CVD events in 227 participants (64 myocardial infarction, 85 angina, 8 cardiac arrest, 58 stroke, 23 CVD death). Proportional hazards models were used to calculate HRs of overall CVD, adjusted for age, sex, ethnicity, standard risk factors and statin use.

Results.
Age and sex-adjusted HRs (95% CI) of CVD for CRP >3 mg/L (vs <1 mg/L) and IL-6 or fibrinogen in the 3
rd
vs 1
st
tertile were 1.71 (1.21–2.42), 1.61 (1.13–2.32) and 1.59 (1.28 –2.28), respectively. Fully adjusted HRs were 1.41 (0.98 –2.04), 1.30 (0.89 –1.91) and 1.17 (0.80 –1.70). Exclusion of angina as an endpoint increased the adjusted HR for CRP (1.63; 1.01–2.63) but not IL-6 or fibrinogen. There were no significant differences of these associations by sex or ethnicity. Within categories of baseline CAC, associations of CRP and IL-6 with CVD events were only present among those with CAC 1–100 Agatston units (table

).

Discussion.
Associations of inflammation factors with future CVD in this study were weaker than in other studies of primarily white participants. Stronger associations among those with low levels of detectable CAC suggest detection of plaque vulnerability with biomarkers in these individuals with modest atherosclerotic burden.

Adjusted HR of CVD for Baseline Inflammation Markers by CAC Category (Agatston Units)
Abstract 485: A Mouse Model of Primary Ciliary Dyskinesia Reveals High Frequencies of Heterotaxy and Complex Congenital Heart Defects
Authors: Tan Serena Y , Leatherbury Linda , Rosenthal Julie , Zhao Xiao-Qing , Lo Cecilia W
Published: July 2021

Specification of left-right asymmetry is essential for formation of the four chamber heart and separate systemic and pulmonary circulation. Previous studies suggest monocilia at the embryonic node is required for left-right patterning. This patterning is perturbed in primary ciliary dyskinesia (PCD) where situs defects and bronchiectasis are observed, often due to ciliary dysfunction arising from dynein mutations. Most PCD patients exhibit situs solitus or situs inversus totalis, but heterotaxy with complex congenital heart disease (CHD) appears to be rare, reported as 6%. We recovered a mouse mutation in dynein Mdnah5 that disrupts ciliary function. Homozygote mutants exhibit situs phenotypes consistent with PCD in humans. To assess the frequency of CHD associated with PCD, we harvested16 litters of embryos. All wildtype and heterozygous offspring (89) showed normal body situs. Of the 21 (19%) homozygous mutants obtained, 6 had situs solitus, 7 situs inversus and 8 heterotaxy, with heterotaxy being any situs deviation in the cardiac, pulmonary or visceral anatomy. Of the heterotaxic embryos, 3 had levo and 5 dextrocardia. Histology and 3D reconstruction showed 7 of the heterotaxy embryos had complex CHD, which included atrial isomerism, superior-inferior ventricles (Figure

), malposition of the great arteries, AV cushion defects, and azygous continuation of the inferior vena cava. These results show a much higher frequency of heterotaxy and complex CHD than previously reported for PCD (38% vs. 6%), suggesting PCD patients should be screened for CHD. The high incidence of CHD associated with PCD indicates ciliary function may have other roles in cardiovascular patterning.
Abstract 486: Down-regulation of type 1 cGMP-dependent Protein Kinase by the ubiquitin/proteasome pathway
Authors: DEY NUPUR , Busch Jennifer L , Francis Sharron H , Corbin Jackie D , Lincoln Thomas M
Published: July 2021

Type 1 cGMP-dependent protein kinase (PKG-I) is a widely expressed serine/threonine protein kinase, and is a major mediator of nitric oxide (NO) signaling in vascular smooth muscle cells (VSMC). PKG-I level is highly variable in VSMC and several studies have shown that atherogenic inflammatory cytokines lower the steady-statel levels of PKG-I. The mechanism of action of down-regulation is not well defined, but induction of type II NO synthase (iNOS) and subsequent persistent elevation of cGMP appear to contribute to PKG-I down regulation. In the present study, we examined the role of the ubiquitin/proteasome pathway in PKG-Iα down-regulation in response to elevated cGMP. Incubation of cultured VSMC with 8-Br-cGMP for 6–12 hr lowered PKG-I expression as assessed by western blotting. To further examine the mechanism, Cos7 cells, which do not express PKG-I mRNA or protein, were transfected with PKG-Iα/pcDNA vector and incubated with 8-Br-cGMP. 8-Br-cGMP suppressed PKG-Iα protein level in Cos7 cells (half-maximal concentration = 250 μM). Pretreatment of these cells with the proteasome inhibitor, MG132, followed by 8-Br-cGMP treatment prevented the decline suggesting the involvement of the ubiquitin/26S proteasome pathway. Immunoprecipitation of PKG-I followed by immunoblotting with anti-ubiquitin revealed multiple ubiquitinated PKG bands in the 8-Br-cGMP treated samples but not in untreated samples. Ubiquitination and down-regulation were also inhibited by the specific PKG-I catalytic inhibitor DT-2, suggesting the possible involvement of PKG autophosphorylation in the 8-Br-cGMP induced down-regulation. Mutation of the PKG-Iα autophosphorylation sites to alanines was performed to identify the phosphorylated site responsible for cGMP-dependent ubiquitination. In contrast to wild type PKG-Iα, PKG-Iα S64A, but not the S50A mutant, was not down-regulated by 8-Br-cGMP suggesting that autophosphorylation of serine-64 is required for the ubiquitination and down-regulation of PKG-I. Autophosphorylation and cGMP-mediated down-regulation of PKG-I may be an important mechanism to control excess cGMP signaling in VSMC.
Abstract 3658: The Prevalence of Depression and Anxiety among Persons Aged 45 Years and Older by Cardiovascular disease Status, 2006
Authors: Fan Amy Z , Strine Tara W , Jiles Ruth , Mokdad Ali H
Published: July 2021

Depression and anxiety commonly occur after nonfatal cardiovascular events. It is imperative to learn the extent of depression and anxiety among middle-aged and elder adults with cardiovascular disease at the population level. The Behavioral Risk Factor Surveillance System (BRFSS) is an ongoing, state-based, telephone survey of non-institutionalized adults. In 2006, an Anxiety and Depression Module (ADM) was administered in 38 States, Puerto Rico, the US Virgin Islands, and the District of Columbia. Eight ADM questions were adapted from the validated Patient Health Questionnaire 8. A standardized summary depression severity score from the eight questions was dichotomized as ≥10 or <10. A score ≥10 has been shown to have an 88% sensitivity and specificity for major depression. Two questions assessed lifetime diagnosis of depressive and anxiety disorders. Cardiovascular disease (CVD) was assessed using three questions on coronary heart disease (including angina and myocardial infarction) and stroke. The analysis was performed using SUDAAN 9.0 to account for the complex sampling design of BRFSS. Adjusted prevalence ratio (APR) was obtained by the LOGLINK procedure after adjustment for age, sex, race/ethnicity, education level, marital status and employment status. Results showed among persons aged 45 years and older (n=129,499), the prevalence of a CVD history was 15.3% (95% CI=14.9%-15.7%). The prevalence of CHD and stroke was 12.4% (95% CI=12.0%-12.7%) and 5.0% (95% CI=4.8%-5.2%), respectively. The prevalence of a current depression severity score ≥10 was 7.7% (95% CI=7.3%-8.0%). The prevalence of a lifetime diagnosis of depressive and anxiety disorders was 16.2% (95% CI=15.8%-16.6%) and 11.0% (95% CI=10.6%-11.3%) respectively. Persons with a CVD history were more likely to have a depression severity score ≥10 (15.8% vs. 7.1%, APR [95% CI] = 1.69 [1.54 –1.85]) or have a lifetime diagnosis of depressive (22.3% versus 15.1%, APR [95% CI] = 1.56 [1.45–1.67]) or anxiety disorders (16.6% versus 10.0%, APR [95% CI] = 1.46 [1.37–1.54]). The findings underscore the importance of assessing mental health status in chronic care and management of cardiovascular disease.
Abstract 3667: Comparison of Risk Profiles between Survivors and Victims of Sudden Cardiac Death of an Acute Coronary Event
Authors: Kaikkonen Kari S , Kortelainen Marja-Leena , Huikuri Heikki V
Published: July 2021

Introduction.

There is little information on the specific risk factors leading to sudden cardiac death (SCD) during an acute coronary event, because the risk variables may overlap with those of non-fatal coronary event. This study was designed to compare the risk profiles of SCD victims and survivors of an acute coronary event.

Methods and Results.

A case-control study included consecutive victims of SCD (n=425, mean age 64±11 years) verified to be due to an acute coronary event at medicolegal autopsy and consecutive patients surviving an acute myocardial infarction (AMI, n=644, mean age 62±10 years). Common cardiovascular risk factors, cardiac hypertrophy, and severity of coronary artery disease (CAD) were assessed in both groups. Family history of SCD (odds ratio 1.5, 95% CI 1.0 to 2.2, p=0.03), male gender (odds ratio 1.8, 95% CI 1.3 to 2.4, p<0.001), current smoking (odds ratio 2.0, 95% CI 1.5 to 2.6, p<0.001), cardiac hypertrophy (odds ratio 3.0, 95% CI 2.3 to 3.9, p<0.001) and 3-vessel CAD (odds ratio 5.4, 95% CI 3.6 to 8.2, p<0.001) were more common among the victims of SCD as compared to survivors of AMI. On the contrary, history of hypercholesterolemia (p<0.001) was less common among the SCD victims. There was a cumulative increase of risk of being a SCD victim vs. AMI survivor when more than one risk factor was present, the odds ratio being 44.3 (95% CI 8.0 to 246.7) in a current male smoker with a family history of SCD and cardiac hypertrophy. When 3-vessel CAD was added to the combined risk score, all subjects (7% of the SCD victims) were in the group of SCD giving a 100% sensitivity and specificity, respectively, in differentiating between the SCD victims and AMI survivors.

Conclusions.

There are specific features that differentiate the victims of SCD from survivors of an acute coronary event. Clustering of several variables, such as family history of SCD, smoking, cardiac hypertrophy, and 3-vessel CAD indicate a very high risk of SCD.
Abstract 3668: Predictors of Four-Year Incident Arterial Hypertension From Initial Prehypertension: The Strong Heart Study.
Authors: De Marco Marina , Chinali Marcello , Roman Mary J. , Lee Elisa T. , Russell Marie , Howard Barbara V. , de Simone Giovanni , Devereux Richard B.
Published: July 2021

Background: Pre-hypertension (defined by JNC-VII) frequently evolves to arterial hypertension (HTN) and is recently shown to increase cardiovascular risk, especially in diabetics. It is unclear which metabolic and cardiac characteristics predict development of HTN in pre-hypertensive subjects.

Methods: 627 pre-hypertensive participants in the Strong Heart Study, free of anti-hypertensive treatment and without prevalent cardiovascular disease or significant valve disease, were studied (64% women; 41% diabetic; 58±7 yrs). All participants underwent complete echocardiographic, anthropometric and laboratory testing. We evaluated 4-year incidence of HTN using anthropometric and metabolic profile as first predictors, and echocardiographic indices thereafter.

Results: Four-year incidence of HTN was 41%. Preliminary analysis identified diabetes (DM by ADA criteria) as a significant predictor of incident HTN (53% among participants with DM vs 33% in non DM; OR= 2.02, 95% CI=1.42–2.88; p<0.001). Accordingly, additional analysis was performed separately in participants with or without baseline DM. After adjusting for age, gender, and heart rate, strongest predictor of HTN in DM was baseline systolic blood pressure (OR= 1.07/mmHg, 95% CI=1.03–1.12; p=0.001) with weaker effect of echocardiographic relative wall thickness (p=0.03). In non-DM, independent predictors of HTN were systolic blood pressure (HR= 1.08/mmHg, 95% CI=1.04–1.12; p<0.001), non-HDL cholesterol (HR= 1.01/mg*dL-1, 95% CI=1.00–1.01; p=0.01) and high LV mass index (OR=1.04 g/m2.7, 95% CI=1.01–1.07; p= 0.007). Higher Doppler stroke volume and total peripheral resistance also entered alternative models without LV mass (each p<0.05).

Conclusion: In a population of pre-hypertension adults we demonstrate high incidence of HTN (41%). Independent predictors of HTN at 4-year follow-up are presence of diabetes and higher baseline systolic blood pressure. In non-DM, LV mass index is an indipendent predictor of incident HTN in addition to baseline systolic blood pressure and non-HDL cholesterol.
Abstract 3685: Reduced Systemic Arterial Compliance is an Independent Predictor of Mortality in Patients with Diabetes
Authors: Mohty Dania , Pibarot Philippe , Poirier Paul , Dumesnil Jean G.
Published: July 2021

Background:
Diabetes is associated with accelerated vascular calcification and stiffening of the arteries. Reduced systemic arterial compliance (SAC) is regarded as a major factor in the development of hypertension, contributing to increased left ventricular afterload and myocardial oxygen demand and reduced coronary flow reserve. We thus hypothesized that reduced SAC is an independent predictor of mortality in patients with diabetes.

Methods:
We retrospectively analyzed data of 528 consecutive patients with type 2 diabetes who had a Doppler-echocardiographic exam in our institution. Blood pressure was measured in all patients at the time of echocardiography. SAC was calculated as the ratio of stroke volume index to arterial pulse pressure.

Results:
Follow up was completed in 97% of patients and mean follow-up time was 2.9±1.2 years. Mean age was 66±11 years with 68% males and 68% with coronary artery disease (CAD). Fifty percent of the patients had markedly reduced SAC on the basis of the cut-off value (SAC <0.6 ml/m
2
/mmHg) previously reported to be associated with adverse outcome in patients with hypertension. Patients with reduced SAC were significantly older (68±11 vs. 65±10, p=0.002) and had a higher prevalence of hypertension (78 vs. 22%, p<0.0001) and lower LV ejection fraction (51±15 vs. 57±13%, p=0.001). The prevalence of male gender, CAD, and obesity assessed with body mass index (BMI) was similar in patients with reduced SAC compared to those with higher SAC values. Five-year survival was significantly lower in patients with reduced SAC (68±5 vs. 87±4%, p<0.005). After adjusting for age, gender, LV ejection fraction, CAD, BMI, and blood pressure, reduced SAC remained a powerful and independent predictor of total mortality (Hazard ratio: 1.70 95% Confidence interval: 1.14 –2.58; p=0.008).

Conclusion
: Reduced SAC is encountered frequently in patients with type 2 diabetes and is a major risk factor for total mortality in this population. The SAC, which is easily measurable in the context of routine echocardiographic exam, should be taken into consideration when evaluating these patients with regards to prognosis and treatment.

Funded by:
Québec Heart Institute Foundation
Abstract 3687: Microcirculatory Changes in Diabetic Subjects
Authors: Freeman Jenny , Nouvong Aksone , Mohler Emile , Davis Brian , Medenilla Elizabeth , Tajaddini Azita , Cornejo Martha , Arriga Wendy , Panasyuk Svetlana , Schomacker Kevin , Veves Aristidis
Published: July 2021

INTRODUCTION: Hyperspectral Technology cutaneous Oxygenation Monitoring (HTcOM) quantifies oxyhemoglobin (HT-Oxy) & deoxyhemoglobin (HT-Deoxy) on a pixel by pixel basis, providing a scan that shows microcirculatory patterns of tissue oxygenation. Here, we test the use of HTcOM to define patients at higher risk of diabetic complications based on systemic microcirculatory changes.

METHODS: Data were extracted from an ongoing NIH/NIDDK study, following 210 type 1 & type 2 diabetic subjects at high risk for foot ulceration & 66 with ulcers for 18 months. HTcOM values were measured from volar forearm, palm & foot dorsum. Subjects with diabetic foot ulcers during the study were compared to high risk diabetics without ulcers. HT-Oxy and HT-Deoxy data was used as the primary basis for determining systemic microvascular disease in diabetic subjects.

RESULTS: Interim data was analyzed from 162 type 1 & 2 diabetics. Subjects with ulcers were compared to those without ulcers. Diastolic blood pressure, HbA1c, HDL & neuropathy disability scores were different between the 2 groups. Lower HT-Oxy was found in forearms & palms for the ulcer group when compared to the group without ulcers. Significant differences were also seen for the dorsum, but only when analyzing paired difference.

CONCLUSIONS: Previous work demonstrated that HTcOM could differentiate between subjects without diabetes, low risk diabetics & high risk diabetics. The current work demonstrates additional capabilities of HTcOM to discriminate even within the high risk group. Subjects with poorer systemic microcirculation as manifested by lower HTcOM readings on the forearm were significantly more likely to have or develop a foot ulcer than other subjects considered at high risk by standard clinical assessment. HTcOM provides for the first time, the possibility to perform a non-invasive assessment of the severity of systemic microvascular disease associated with diabetes progression.

Linear Regression Mixed Effects Model Results
Abstract 3692: Tight Diabetic Glycemic Control Reduces the Risk of Cardiovascular Disease Only in Individuals with the Hp 2–2 Genotype
Authors: Blum Shany , Milman Uzi , Shapira Chen , Miller-Lotan Rachel , Anbinder Yefim , Alshiek Junia , Bennett Lawrence , Kostenko Maria , Landau Michele , Keidar Shlomo , Levy Yishai , Khemlin Alexander , Radan Arman , Levy Andrew P
Published: July 2021

Background.
The Haptoglobin (Hp) gene is polymorphic in man with two classes of alleles denoted 1 and 2. Several cross sectional and retrospective analysis have suggested that the Hp genotype may be a major determinant of susceptibility to diabetic CVD. We sought to examine this relationship in a prospective population based study.

Methods.
We recruited over 3000 individuals 55 years of age or older with DM from 47 primary health care clinics of the Clalit Health Plan in Northern Israel and obtained a Hp genotype on all of these individuals. The prevalence of CVD at baseline was 25%. Patients were followed for two years, for the primary composite outcome of the study which was incident non-fatal myocardial infarction, stroke and CV death.

Results.
We found that the Hp 2–2 genotype was associated with a highly significant increase in the incidence of myocardial infarction, stroke and CV death. Moreover, after stratification of patients by baseline HbA1c to those above and below 7.0, representing inadequate or adequate glycemic control as currently recommended by the AHA and ADA, only in Hp 2–2 individuals was poor glycemic control found to be associated with an increased risk of major cardiovascular events.

Conclusions.
Optimal utilization of health care resources for risk factor modification should be focused on DM individuals with the Hp 2–2 genotype. Benefit from tight glycemic control only in a subset of the DM cohort defined by the Hp 2–2 genotype may explain the inability to show a benefit from tight glycemic control on reducing cardiovascular events in the entire DM cohort in multiple prior clinical studies.
Abstract 3695: Obesity-mediated Vascular Injury Stimulates Progenitor Cell Mobilization
Authors: Sher Salman , Porkert Markus , Zeigler Thomas R , Pedersen Margaret F , Sutcliffe Diane , Taylor W Robert , Jones Dean P , Dunbar Sandra B , Hooper Craig , Harrison David , Alexander R Wayne , Quyyumi Arshed A
Published: July 2021

Recent data suggest that bone marrow derived endothelial progenitor cells contribute to endothelial repair after damage. We investigated whether obesity modulates the number and function of progenitor cells, and whether lifestyle intervention with a healthy diet influences this effect. We hypothesized that obesity-mediated vascular injury stimulates progenitor cell mobilization.

Methods
Peripheral blood mononuclear cells were cultured on fibronectin plates for 7 days and the number of colony forming units (CFUs) with endothelial-type cells at their periphery were counted. 28 lean healthy subjects were compared with 30 overweight/obese age-and sex-matched non-smokers on a high saturated fat (> 10%) American style diet. Twenty obese subjects were then randomized to receive either a Mediterranean-style (MED) diet (n=11) or the control regular American diet (n=9) for 2 months. Endothelium-dependent and -independent function was measured by brachial reactivity testing at baseline, 1 and 2 months.

Results
CFUs were significantly higher in overweight/obese compared to lean subjects (74±42 vs 23±10, p<0.001), even after adjustment for other risk factors. When overweight/obese subjects were treated with a MED diet, CFUs reduced significantly, a change that was not observed in the controls (Table

). There was a simultaneous improvement in brachial flow-mediated vasodilation but not endothelium-independent function in the MED group. No changes were observed in controls(Table

).

Conclusion
Endothelial precursors are stimulated in obese compared to lean subjects. Dietary alteration to a MED diet resulted in improvement in endothelial function and reduced mobilization of endothelial precursors. These observations suggest that endothelial injury in obesity provokes a compensatory mobilization of endothelial progenitor cell population that may help repair damage to the endothelial lining.
Abstract 3696: Decreased Number Of Circulating Progenitor Cells In Obesity -Beneficial Effects Of Weight Reduction
Authors: Muller-Ehmsen Jochen , Braun Daniela , Schneider Thorsten , Pfister Roman , Grundmann Franziska , Scheid Christof , Flesch Markus
Published: July 2021

Aims:
Cardiovascular risk factors are associated with decreased levels of circulating progenitor cells (CPC). The aim of this study was to determine whether the number of CPC is an independent correlate of Body-Mass-Index (BMI) and whether weight loss leads to an increase of CPC.

Methods:
CD34 positive and KDR/CD34, CD133/CD34 and CD117/CD34 double positive cells were measured by FACS in peripheral blood of 149 volunteers (52.5±0.1 years, BMI 21.5–52.7 kg/m
2
, mean 31.6±0.03 kg/m
2
) participating in a weight reduction program offered by German pharmacies. In addition, carotid intima media thickness and brachial artery flow mediated dilatation were determined. After a diet and sports program for 6 months, 86 representing subjects were re-evaluated (mean weight loss 5.8±0.1 kg).

Results:
There was an inverse correlation between BMI and CPC. For subjects with BMI>34.1 compared to BMI<28.1 (4
th
vs. 1
st
quartile) cell counts were: CD34+: 137.7±1.6 vs. 187.0±1.8; KDR/CD34: 17.3±0.7 vs. 55.8±2.0; CD133/CD34: 70.2±1.6 vs. 129.2±1.7; CD117/CD34: 93.1±2.1 vs. 142.7±1.7, all per million leucocytes; p< 0.01 for all parameters). The decrease in CPC in obesity held true not only for the absolute cell numbers, but also for the relative fractions of KDR, CD133 and CD117 positive cells within the CD34 + cells, indicating a specific down regulation of these progenitor cell types. Intima media thickness increased in dependence from BMI (p< 0.001) and was inversely correlated with the number of circulating CD34 positive cell (p< 0.05). After diet, there was a significant increase of CD34 and CD117/CD34 positive cells in subjects whose reduction in BMI was greater than 2.5 kg/m
2
(4
th
quartile), which was accompanied by a decrease in intima media thickness (p< 0.05) and an improvement in forearm dilatory response (p < 0.01). Increase in the number of CPC was independent from whether weight loss was achieved by increased physical exercise or by reduced calory intake only.

Conclusions:
Obesity is associated with decreased numbers of CPC, increased intima media thickness and impaired endothelial function. Diet and weight loss lead to an increase in circulating progenitor cell count, which might contribute to regression of intima media thickness and improved endothelial function.
Abstract 491: Triggered Sarcoplasmic Reticulum Ca Release Mediated By Na-ca Exchanger And Brain Na Channels In Rabbit Ventricular Cells
Authors: Savio-Galimberti Eleonora , Goldhaber Joshua I , Bridge John H
Published: July 2021

We tested the hypothesis that sarcoplasmic reticulum (SR) Ca release triggered by cardiac action potentials is significantly affected by Na influx through brain isoforms of the Na channel. These channels are reportedly located in the t-tubules and could therefore activate reverse Na-Ca exchanger (NCX) and contribute to triggered release. In the complete absence of a Na gradient (Li replacement) Ca transients evoked by action potentials were delayed, their upstrokes slowed and their peak values diminished (SR Ca content not depleted under these conditions). Ca spikes recorded under these conditions occurred at significantly lower probability and became asynchronous (see figure

). Tetrodotoxin 200 nM (this concentration selectively blocks brain Na channel isoforms Nav 1.1, 1.3 and 1.6) reduced the magnitude and rate of rise of Ca transients in a way that resembled the effect of removing the Na gradient. We suggest that early activation of brain type Na channels leads to elevation of Na in the dyadic cleft. This causes reverse NCX, which primes the junction with Ca before L-type Ca channels (LCC) have opened. Since the junction has been primed with Ca, short LCC openings can effectively gate ryanodine receptors (RyRs). Because these LCC openings have short latencies and occur with high probability they produce spikes with short latencies at high probability. In the absence of a Na gradient longer LCC openings are required to fill the junction and gate RyRs. These occur with lower probability and greater latency. We conclude that brain Na channels together with NCX significantly increase LCC-RyR coupling fidelity and synchronize spikes.
Abstract 3707: Selenium Concentration and Cardiovascular Events in Patients with Coronary Artery Disease
Authors: Sinning Christoph R , Lubos Edith , Schnabel Renate , Sinning Jan-Malte , Wild Philipp S , Zeller Tanja , Bickel Christoph , Espinola-Klein Christine , Lackner Karl J , Tiret Laurence , Muenzel Thomas F , Blankenberg Stefan
Published: July 2021

Introduction:
Selenium is an essential trace element with important antioxidative properties. The aim of this study was to evaluate the relative risk of cardiovascular mortality according to increasing concentrations of selenium and a possible protective effect of high selenium concentrations against oxidative stress in patients with established coronary artery disease.

Methods:
In this substudy of the prospective Athero
Gene
survey, 1867 patients were included. These patients could be stratified according to the diagnosis into stable angina pectoris (SAP, n=852), acute coronary syndrome (ACS, n=879) and exclusion of relevant coronary artery disease (NoCAD, n=123).

Results:
Low selenium concentration is associated with an increased relative risk for cardiovascular mortality. When the collective with ACS is stratified into tertiles of rising selenium concentration, the survival curves according to the Kaplan-Meier-Method (Log-Rank Test: P=0.0001) reveal an adverse outcome. In contrast, in patients with SAP was no association between the selenium concentration and outcome (P=0.35) had been observed. In a fully adjusted Cox proportional hazards model encompassing classical risk factors, medication and laboratory markers, thirds of increasing selenium concentration were associated with a protective effect in patients with ACS (tertiles: HR: 0.362, 95% CI: 0.149–0.878, P=0.025). In a Cox backward-stepwise regression analysis encompassing sixteen variables of cardiovascular risk prediction, one increment increase in selenium concentration decreased the risk of cardiovascular mortality in patients with ACS (HR:0.746, 95%CI: 0.602–0.926; P-Value: 0.008).

Conclusion
: Increased selenium concentration is related to an improved outcome after the acute event. This data encourages the concept of selenium administration in patients with ACS.
Abstract 3717: Corrected Qt Interval (qtc) Is Prolonged In Metabolic Syndrome Population
Authors: Li Weiju , Bai Yongyi , Sun Kai , Chen Jingzhou , Wang Yibo , Zhang Weili , Song Xiaodong , Fan Xiaohan , Wang Shuxia , Yang Xiaomin , Han Yunfeng
Published: July 2021

Background
: Prolonged corrected QT interval (QTc) is a risk factor for cardiovascular disease, recent studies suggested that patients with metabolic syndrome had significantly higher values of QTc, but those studies were conducted in small sample, the result should be verified in large population.

Purpose
: The study is to evaluate the relationship between QTc and metabolic syndrome in large population and to elucidate the possible pathophysiological mechanism.

Methods:
The date was collected in a hypertensive survey in rural China, a total of 5467 individuals (men 3667, women 1800), aged from 20 to 80 years, were enrolled. Subjects with history of coronary heart disease, valvular heart disease, stroke, hepatic, renal, thyroid diseases and all kinds of arrhythmia (recorded by 12 lead ECGs) were excluded. Electrocardiogram was recorded and the value of QTc was calculated using Bazett’s equation. All individuals had ultrasonic echocardiograph examination and blood test. Using revised NCEP-ATPIII definition, 2271 individuals were diagnosed with metabolic syndrome, 3128 were non-metabolic syndrome.

Results:
Both men and women individuals with metabolic syndrome had longer QTc than those with no metabolic syndrome (404.1±30.7ms vs 407.6±31.5 ms, p<0.05; 412.3±32.1 ms vs 417.5 ±32.4ms, p<0.001 respectively). The value of QTc increased with the number of abnormal metabolic parameters. After adjusted age and sex, QTc is negatively correlated to serum potassium concentration and positively correlated with posterior left ventricular wall and intraventricular septum in both men and womem.

Conclusion:
Metabolic syndrome, even its single component is a risk factor for prolonged QTc. As metabolic syndrome individuals have lower serum potassium concentration and thicker posterior left ventricular wall and intraventricular septum than non-metabolic syndrome individuals, we propose that low serum potassium concentration and myocardial hypertrophy might play important roles in the development of prolonged QTc in metabolic syndrome.
Abstract 3725: Simvastatin but Not Pravastatin Affects Sleep: Findings from the UCSD Statin Study
Authors: Golomb Beatrice A , Kwon Edwin K , Criqui Michael H , Dimsdale Joel E
Published: July 2021

Background
: Case reports have suggested possible effects of lipophilic statins on sleep in some subjects. Most randomized studies evaluating the effect of statins on sleep have had small sample size and short duration (≤ 6 weeks). Whether statins affect sleep on average, favorably or adversely, has been unclear.

Goal
: To assess the effects of lipophilic and hydrophilic statins on sleep.

Subjects
: 1016 adult men and women without diabetes or heart disease, with LDL-cholesterol 115–190mg/dL.

Design
: Randomized double blind placebo-controlled trial of simvastatin 20mg, pravastatin 40mg or placebo for 6 months. Sleep was a prespecified secondary outcome. It was assessed by both an adaptation of the Leeds sleep scale (a visual analog scale of sleep quality); and a rating scale of sleep problems. Both items were measured at baseline and on-treatment.

Analysis
: Baseline comparability of randomization groups including sleep measures was affirmed. T-test of mean on-treatment sleep scores across randomization groups was performed. This complemented regression analyses, adjusted for baseline values of the respective sleep assessment.

Results
: Groups were comparable at baseline on variables including both sleep measures. Simvastatin use was associated with significantly worse sleep quality, and significantly greater reported sleep problems than either pravastatin or placebo, by t-test and regression analyses. Pravastatin did not differ significantly from placebo on any sleep outcome.

Conclusion
: Findings were compatible with the hypothesis that statins may impair sleep in some subjects, and that this impairment may arise selectively with lipophilic statins.

Table 1.

Effects of Statins on Sleep: Regression Analysis
Abstract 3734: Glucose-Insulin-Potassium Infusion in Patients with Acute Myocardial Infarction treated with Reperfusion Therapy Does Not Reduce the Risk of Cardiovascular Events: A Pooled Meta-analysis of Randomized Controlled Trials
Authors: Katragadda Srikanth , Saha Sandeep A , Arora Rohit R
Published: July 2021

Background:
Metabolic modulation of ischemic myocardium using a glucose-insulin-potassium (GIK) infusion has been studied in patients with acute myocardial infarction treated with reperfusion therapy, but the results have been conflicting. We conducted a systematic review and meta-analysis of randomized placebo-controlled trials evaluating the utility of GIK in the prevention of adverse cardiovascular outcomes in patients with acute myocardial infarction who underwent reperfusion therapy.

Methods:
A total of 19,222 patients from 6 randomized placebo-controlled clinical trials were analyzed using pooled meta-analysis techniques, and relative risks at the end of one month were computed for various adverse cardiovascular outcomes. Statistical significance was determined using the
z
-test (two-sided alpha-error <0.05).

Results:
The use of GIK did not significantly reduce the risk of death within the first month among patients with acute myocardial infarction treated with reperfusion therapy (p=0.40), and did not differ among those treated with thrombolytic agents (p=0.54) or those treated with primary coronary angioplasty (p=0.38). The risk of re-infarction within the first month was also not significantly reduced (p=0.32), nor were the risk of development of heart failure (p=0.40) or the need for invasive coronary revascularization (p=0.76).

Conclusions:
Among patients with acute myocardial infarction who are treated with reperfusion therapy, the use of GIK infusion has no significant effect on mortality or the occurrence of adverse cardiovascular events within the first month.
Abstract 3736: Glucose Lowering Treatment is Prognostically Important in Patients with Coronary Artery Disease and Newly Detected Diabetes Mellitus. A report from a Euro Heart Survey
Authors: Anselmino Matteo , Öhrvik John , Malmberg Klas , Rydén Lars
Published: July 2021

Patients with coronary artery disease (CAD) and newly diagnosed diabetes mellitus (NDM) are at increased risk for cardiovascular events (CVE= death, myocardial infarction or stroke). This report from the Euro Heart Survey on Diabetes and the Heart relates glucose lowering (GL) treatment to cardiovascular prognosis.

Methods
3940 patients with CAD were enrolled at 110 centers in 25 countries, of whom 1425 (36%) had known DM and 2515 (64%) were glucometabolically characterized with an oral glucose tolerance test (WHO 1999) or fasting blood glucose (ADA 2004) and followed for one-year with respect to CVE.

Results
452 patients had NDM of whom 77 (17%) were started on pharmaceutical GL treatment (insulin 5%, oral glucose lowering drugs 94%, both 1%) while 375 (83%) not received any GL drugs. Baseline characteristics did not differ in patients receiving pharmaceutical GL treatment or not. None of the patients receiving pharmaceutical GL treatment died compared to 25 of those who did not (p=0.002). Myocardial infarction and stroke occurred in one vs. 13 and one vs. five patients respectively. Kaplan-Meier curves for CVE in patients receiving GL drugs (full) or not (empty) are shown in the figure

. Adjusting for age, sex, previous cardiovascular disease and use of evidence based medications in a Cox proportional hazard regression, patients on pharmaceutical GL treatment had a lower CVE hazard ratio during follow-up (HR 0.22, 95%CI 0.05–0.97; p=0.041) compared to those not on GL therapy.

Conclusion
There was a striking decrease in event free survival in NDM patients prescribed pharmacological GL therapy following diagnosis underlining the importance to detect and treat such perturbations.
Abstract 3746: Association of Gamma ′ Fibrinogen with Risk Factors and Prevalent Cardiovascular Disease in the Framingham Heart Study
Authors: Lovely Rehana S , Massaro Joseph F , D’Agostino Ralph B , Benjamin Emelia J , Kazmierczak Steven C , O’Donnell Christopher J , Farrell David H
Published: July 2021

Background:
γ′ fibrinogen is a newly-emerging cardiovascular disease (CVD) biomarker that has shown significant associations with coronary artery disease in small case/control studies. γ ′ fibrinogen is an isoform with an altered γ chain, and constitutes ∼10% of total fibrinogen. Both elevatedγ ′ and total fibrinogen cause fibrinolytic resistance
in vitro
. However, data are lacking from community based studies on the association ofγ ′ fibrinogen with CVD risk factors or with clinical CVD.

Methods:
γ ′ fibrinogen levels were measured using an ELISA assay in 3284 men and women in the Framingham Heart Study Offspring Cohort 7th examination cycle (2002– 05). Associations ofγ ′ fibrinogen were examined using linear regression for continuous CVD risk factors and logistic regression for prevalent CVD and other dichotomous measures.

Results:
The ELISA CV was 9.3% at meanγ ′ fibrinogen levels. Participants (mean age 60 years, 53.4% women) with prevalent CVD (0.297 ± 0.007 mg/ml; mean ± SE) had significantly higher mean concentrations than those without CVD (0.255 ± 0.002 mg/ml). There were significant (all p<0.05) associations betweenγ ′ fibrinogen levels with several cardiovascular risk factors, including age, BMI, systolic blood pressure, diabetes mellitus, cigarette smoking, and total cholesterol, and an inverse association with HDL cholesterol. γ ′ fibrinogen was associated with prevalent CVD with an odds ratio of 1.76 (95% CI 1.06–2.92) for the highest compared to the lowest tertile, after adjustment for all of the above risk factors. As expected, sinceγ ′ fibrinogen constitutes a subset of total fibrinogen, γ ′ fibrinogen was correlated with total fibrinogen. However, if we included bothγ ′ and total fibrinogen in further analyses of association with CVD, the odds ratio was 3.08 (95% CI 1.41–6.72) for the combined tertile of both the highestγ ′ fibrinogen and highest total fibrinogen, an odds ratio that was substantially higher than that for either marker alone.

Conclusions:
γ ′ fibrinogen is associated with multiple CVD risk factors and with prevalent CVD, accounting for CVD risk factors, over and above total fibrinogen alone. Prospective studies are warranted to examine the ability ofγ ′ fibrinogen to predict CVD.
Abstract 3750: Prevalence of Coronary Artery Disease in New York City Police Officers as Predicted by Coronary Artery Calcium Scoring
Authors: See Jia Lin , Wanahita Nikolas , Somekh Nir N , Nelson Stephen E , Barrette Albert , Giedd Kenneth , Bergmann Steven R
Published: July 2021

Background:
Recent studies in police officers and firefighters have shown that physically taxing and psychologically stressful occupations may increase death from coronary artery disease (CAD). The aim of this study was to determine if there is an increased prevalence of CAD among members of the New York City Police Department (NYPD).

Methods:
A total of 2,068 NYPD police officers and detectives underwent electron beam computed tomography for quantitation of coronary artery calcium (CAC) using the Agatston scoring method. The CAC score is known to correlate with the extent and severity of CAD and is predictive of adverse cardiovascular events. The CAC scores were compared with a gender- and age-specific database developed by Hoff et al (also known as the Kondos database). Patients with CAC scores > 400 and those whose scores fall within the upper quartile for gender and age are generally considered to be at increased risk of adverse events.

Results:
Participants’ mean age was 42 ± 6 years and 86% were male. More than 50% of males < 65 and females < 60 years of age had scores below the 50
th
percentile for their age group (Tables

). A subset of 75 individuals (mean age 41 ± 6; 88% male) with known early exposure to the World Trade Center (WTC) collapse were evaluated; they did not have increased CAC scores (data not shown).

Conclusion:
There is not an increased prevalence of CAD among members of the NYPD compared to the general population as assessed with CAC quantitation. Early exposure to the WTC collapse does not appear to increase the risk of premature CAD at five years.
Abstract 3763: Standard-dose Statin Therapy Demonstrates Additional Effects In Diabetic Patients With Normal Cholesterol Levels
Authors: Kojima Sunao , Sakamoto Tomohiro , Kitagawa Akira , Ogawa Hisao
Published: July 2021

Background:

Randomized trials established statins as an agent for prevention of coronary heart disease (CHD). We assessed the hypothesis that standard-dose statin therapy had a beneficial effect in diabetic CHD patients with normal cholesterol levels.

Methods and Results:

To evaluate the effect of statins after percutaneous coronary intervention (PCI) on subsequent cardiovascular events, a prospective, randomized, open, blinded-endpoint trial conducted from 2002 to 2004 at 55 hospitals in Japan. A total of 1,016 patients (301 patients with diabetes mellitus [DM] and 715 non-DM patients) whose total cholesterol levels ranged from 180 to 240 mg/dL was enrolled and randomly assigned to receive any available standard-dose statins within 96 hours after PCI. Clinical parameters were comparable between DM group and non-DM group. The low-density lipoprotein cholesterol (LDL-C) levels were equally decreased after statin treatment in 2 groups (Table

). However, event rate for the primary end point was particularly lower in DM patients with statin treatment than those without statin treatment (Figure).

Conclusions:

Standard-dose statin therapy provides incremental clinical benefit in DM patients with normal cholesterol levels compared with that in non-DM patients. These data suggest that DM patients derive pleiotropic effect from statins, irrespective of lowering effect of LDL-C levels.

Serial changes of LDL cholesterol levels