bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 3219: Influence of Adiposity on Arterial Stiffness in Healthy Children
Authors: Sakuragi Satoru , Abhayaratna Katrina , O’Reilly Christine , Srikusalanukul Wichat , Gravenmaker Karen , Budge Marc , Telford Richard , Abhayaratna Walter P
Published: July 2021

Childhood obesity is increasingly prevalent in the community and is related to adverse cardiovascular outcomes during adulthood. Identification of intermediary markers of preclinical cardiovascular disease may identify high-risk children who would benefit greatest from primary prevention measures. In this study, we evaluated the relationship between adiposity on arterial stiffness in healthy children. In 596 healthy children (mean age 10.1 +/− 0.3 years; 51% boys), we measured body mass index (BMI) and waist circumference (WC). Percentage body fat (%BF) was quantitated by dual-energy x-ray absorptiometry (DEXA). Insulin resistance was assessed by a fasting insulin level and homeostasis model assessment as an index of insulin (HOMA-IR). Carotid-femoral pulse wave velocity (PWV), an index of aortic stiffness, was estimated by applanation tonometry. Compared to girls, boys were older (10.1 vs 10.0 years, p=0.01); and had higher WC (61 vs. 60 cm, p=0.02), lower %BF (24% vs. 29 %, p<0.001), similar BMI (18.0 vs. 18.5, p=0.05) and lower PWV (4.4 vs 4.5 m/sec, p<0.001). In univariate analysis, BMI (ρ=0.26 and ρ=0.31), WC (ρ=0.32 and ρ=0.26) and %BF (ρ=0.23 and ρ=0.30) were correlated positively with PWV in boys and girls, respectively (all p<0.001). After adjustment for age, systolic blood pressure, mean arterial pressure and heart rate, BMI, WC and %BF were significantly associated with PWV (p<0.01) (Table

). HOMA-IR and fasting insulin level were not predictors of PWV (p>0.07 for both). Increased adiposity is related to arterial stiffness in healthy children, independently of blood pressure and heart rate. Further studies are required to evaluate whether public health efforts to promote healthy lifestyles and weight loss in children will reduce arterial stiffness, attenuate the progression of subclinical cardiovascular disease, and prevent the development of subsequent cardiovascular events in the community.

Table:

Separate Multivariable Models relating Predictor Variable to PWV
Abstract 3227: Contribution Of Known Genetic Factors To Increased Risk Of Type-2 Diabetes In Indian Asians
Authors: Chambers John , Elliott Paul , Zhang Weihua , Kooner Jaspal S
Published: July 2021

Background.
Type-2 diabetes (T2D) is 2– 4 fold more common amongst Indian Asians than North American and European whites, and is a major contributor to two-fold higher cardiovascular disease mortality in Asians. We investigated whether genetic variation in the validated T2D genes, contributes to the increased risk of T2D amongst Indian Asians, compared to European whites.

Methods.
We examined the association of genetic variants in the 16 validated T2D genes with T2D amongst 9,776 Indian Asian and 4,407 European white men and women, aged 35–75 years, participating in the London Life Sciences Prospective Population (LOLIPOP) study. Genotyping was performed by competitive allele-specific PCR (KASPar).

Results.
Indian Asians had higher T2D prevalence (20.9% vs 8.7%, P<0.001), despite lower age (50.3±10.9 vs 52.1±11.6, P<0.001) and body mass index (26.9±4.1 vs 27.6±4.7, P<0.001), compared to Europeans. Genotyping confirmed association of
WFS1, SLC30A8, PPARG, IGF2BP2, TCF7L2, JAZF1, CDKN2A/B, HHEX/IDE
and
FTO
with T2D in both populations (P<0.05). Associations of
CDKAL1
,
KCNJ11, THADA, CDC123-CAMK1D, ADAMTS9, TSPAN8-LGR5 or NOTCH2
with T2D did not reach statistical significance. SNP risk allele frequency was higher for six, but lower for nine, in Indian Asians compared to Europeans. In regression analysis, risk of T2D remained 3.6 (95%CI 3.2– 4.1, P<0.001) fold higher amongst Indian Asians compared to Europeans, despite adjustment for age, body mass index and known genetic factors.

Discussion.
Known genetic variants show similar association with T2D, and have similar risk allele frequencies, amongst Indian Asians and Europeans. These genetic factors do not account for the three-fold increased risk of T2D amongst Indian Asians.
Abstract 3234: Both In And Outhospital Worsening Of Renal Function Predict Outcome In Patients With Acute Decompensated Heart Failure
Authors: Damman Kevin , van Veldhuisen Dirk J , Voors Adriaan A , Navis Gerjan , Jaarsma Tiny , Hillege Hans L
Published: July 2021

Purpose.
Renal impairment and inhospital worsening of renal function (WRF) are common in patients with acute heart failure (AHF) and associated with poor outcome. The effect of WRF after discharge on outcome in these patients is unknown.

Methods.
The Coordinating Study Evaluating Outcome of Advising and Counseling in Heart Failure (COACH) included 1049 AHF patients. We assessed estimated glomerular filtration rate (eGFR) by the sMDRD formula and serum creatinine at admission, discharge, and 6 and 12 months after discharge. WRF was defined as increase in serum creatinine >0.3mg/dL. The primary outcome was a composite of all-cause mortality and heart failure admissions.

Results.
Mean age was 71 ± 11 years, 62% were male. Mean eGFR at admission was 56 ± 22 mL/min/1.73m
2
,with mean LVEF 33 ± 14%. Inhospital WRF occurred in 13% of patients, while 19% and 12% experienced WRF from 0 to 6, and 6 to 12 months after discharge, respectively. WRF was in a landmark analysis associated with poor outcome: hazard ratio (HR) 1.39 (1.07 –1.81),
P
<0.05 for inhospital WRF, HR 2.70 (1.65 –4.43),
P
< 0.001 for WRF at 6 months and HR 3.44 (1.81–6.52),
P
< 0.001 for WRF between 6 –12 months (Figure

). In multivariate analysis, after adjustment for age, gender, LVEF, eGFR and NYHA class, WRF at any point in time was associated with worse outcome: HR 1.33 (1.01 –1.75),
P
< 0.05 for inhospital WRF, HR 2.50 (1.47 –4.26),
P
= 0.001 for WRF between 0 – 6 months, and HR 2.81 (1.38 – 5.73),
P
= 0.004 for WRF between 6 –12 months.

Conclusion.
Both in and outhospital worsening of renal function are independently related to poor prognosis in patients with AHF, suggesting that renal function in AHF patients should be monitored long after discharge.
Abstract 3262: Impact of the MESA Arterial Age Calculator Incorporating Coronary Calcium on CHD Risk Estimation
Authors: Munir Jamalah , Bindeman Jody , Bauer Kelly , Byrd Carole , Wu Holly , O’Malley Patrick , Taylor Allen
Published: July 2021

Background: The MESA study recently published a web-based calculator for the computation of arterial age incorporating Framingham risk factors and coronary calcium to integrate the incremental predictive value of coronary calcium within the Framingham risk score, a reference-standard clinical coronary heart disease (CHD) risk calculator. We examined the impact of arterial age on the distribution of CHD risk estimation.

Methods: We applied CHD risk factor data from the Prospective Army Coronary Calcium Project, a screening cohort of 2000 men and women between the ages of 40 and 50, to the MESA Arterial Age calculator (available at www.mesa-nhlbi.org). Subjects were studied with measured CHD risk factors and electron beam CT for the identification of coronary artery calcium. Framingham risk scores (FRS), using the 10 year CHD risk model with and without arterial age, were calculated using the MESA arterial age calculator. An estimate CHD risk between 6 and 20% was categorized as intermediate risk, and compared for the calculations using chronological age, and arterial age.

Results: Demographics of the cohort included mean age 42.9 ± 2.7 yrs, male gender 82%, hypertension 8.0%, systolic blood pressure 123 ± 13 mm Hg, current smoking 7.7%, total cholesterol 203 ± 36 mg/dL, and HDL-C 53 ± 14 mg/dL. Mean FRS was 4.5 ± 3.6%. Coronary calcium was present in 394 subjects (19.7%). Application of the arterial age calculator increased mean age from 42.9 ± 2.7 to 43.6 ± 10.4 years (P < .001), and the mean FRS increased from 4.5 ± 3.6 to 7.3 ± 8.1% (P < .001). Reclassification was seen primarily among male subjects, in whom the mean age (chronological vs. arterial age) increased from 42.9 ± 2.7 to 44.2 ± 11.0 (P < .001) and the prevalence of intermediate CHD risk increased from 26.2% (429 of 1639) to 37.4% (613/1639; P < .001). Among women, mean age (chronological vs. arterial age) was reduced by calcium scoring (42.7 ± 2.6 vs. 40.7 ± 6.3%; P < .001) and a shift to intermediate risk was seen in only 0.6% of subjects (from 10 to 18 out of 349).

Conclusions: Among healthy middle-aged individuals, the MESA arterial age calculator modestly shifts predicted CHD risk estimation, and reclassifies 1 in 9 men from low to intermediate risk. Arterial age was lower than chronological age in women.
Abstract 3268: Ethnic Differences in the 12 Lead -EKG - Relevance to the Cardiovascular Evaluation for Hypertrophic Cardiomyopathy in Athletes
Authors: Rawlins John , Papadakis Michael , Edwards Carey , Basavarajaiah Sandeep , Sharma Sanjay
Published: July 2021

Introduction Cardiac adaptation to intense physical exercise is associated with physiological increases in cardiac dimensions that are reflected on the EKG. The EKG changes in Caucasian athletes (WA) are established, however, there is a paucity of data in black athletes (BA) who constitute an increasing proportion of elite athletes in Western countries. We sought to identify differences (if any) in EKG characteristics between BA and WA participating in similar sporting disciplines.

Methods Between 2007– 8, 222 nationally ranked male BA aged 14 –35 and 496 WA of similar age, size and range of sporting disciplines underwent a EKG and standard 2-D echocardiography. All athletes with a left ventricular wall thickness > 12mm and deep T wave inversion (> −0.2 mV) underwent Holter monitor, exercise stress test, and cardiac MRI to exclude phenotypic features of hypertrophic cardiomyopathy (HCM).

Results Black athletes had a greater prevalence of voltage criteria for left ventricular hypertrophy (LVH) (57% vs 42%; p < 0.005), ST segment elevation (76% vs 33%; p < 0.001) and T wave inversions (25% vs 4%; p < 0.001) compared with WA. ST segment elevation in all athletes was confined to the anterior precordial leads but 50% BA exhibited a unique convex ST segment elevation pattern that was absent in WA. There was no correlation between T wave inversions and LVH at echocardiography or cardiac MRI. Indeed none of the BA with T wave inversions displayed any phenotypic features of HCM.

Conclusion Black athletes exhibit different adaptive responses to exercise than WA. Deep T wave inversions and convex ST segment elevation are common in BA, with or without LVH and may overlap with HCM. These results have significant implications during pre-participation screening. There is the potential risk of generating a false positive diagnosis of HCM and lead to unnecessary exclusion from competitive sport, if data derived from WA, used to identify an abnormal EKG, is incorrectly extrapolated to BA.
Abstract 3276: Consumption Of Fatty Fish Is Negatively Associated With The Risk Of Acute Coronary Syndrome In Healthy Men
Authors: Joensen Albert Marni , Bjerregaard Lone J , Dethlefsen Claus , Jensen Majken K , Johnsen Søren P , Tjønneland Anne , Rasmussen Lars H , Overvad Kim , Schmidt Erik B
Published: July 2021

Consumption of fish has been reported to decrease coronary mortality among subjects with known coronary heart disease (CHD), whereas such an effect is less documented in healthy subjects. Few studies have distinguished between intake of fatty fish (defined as a content of long-chained n-3 polyunsaturated fatty acid, greater than 1 g per 100 g of fish) and intake of lean fish.

Objective
To assess the hypothesis that consumption of fatty fish is negatively associated with the risk of acute coronary syndrome (ACS) in healthy men.

Methods
In the Danish cohort-study
Diet, Cancer and Health
27,178 men between 50 and 64 years of age were enrolled. In a validated food frequency questionnaire, participants gave information on dietary intake of fatty fish. During a mean follow-up period of 7.6 years, we identified all cases from this cohort (n=854) with an incident ACS-diagnosis in the Danish National Patient Registry. Diagnoses were verified through medical record review. In Cox proportional hazard models, we adjusted for several well established risk factors for CHD.

Results Conclusion
The risk of ACS was 30% lower among men in the highest 4 quintiles of fatty fish consumption, compared with men in the lowest quintile, in this large Danish cohort study. There was no dose-response association.
Abstract 4985: Are All Patients Considered “Low Risk” for Coronary Heart Disease Really Low Risk? An Analysis from the Atherosclerosis Risk in Communities (ARIC) Study
Authors: Nambi Vijay , Chambless Lloyd , Folsom Aaron R , Hu Yijuan , Mosley Tom , Volcik Kelly , Boerwinkle Eric , Ballantyne Christie M
Published: July 2021

Low risk for coronary heart disease (CHD) is defined by ATP III as a 10 year risk of <10%. There have been suggestions, however, that a 10 year CHD risk of 5–10% be considered as intermediate risk. The addition of carotid intima media thickness (CIMT) has been shown to improve CHD risk prediction when added to traditional risk factors (TRF) (age, gender, high density lipoprotein cholesterol, total cholesterol, diabetes, hypertension and cigarette smoking) in the ARIC study. We investigated the absolute event rates with and without the addition of CIMT to TRF in the ARIC study and determined the impact in the 0–10% risk group. Participants in the ARIC study (n=13145) without baseline CHD or stroke and with CIMT measurements available were included for this analysis. Using Cox proportional hazards models the participants were classified into various risk categories using TRF and further classified by sex specific CIMT (categorized as <25
th
, 25
th
to 75
th
and >75
th
percentile). The absolute event rates were then described in each group (table

). Over a mean follow up of 13.8 years, 1601 (12.2%) individuals had incident CHD events. Approximately 31% of these incident CHD events were in the 5–10% risk group which made up 28% of the study while only 16% of the incident CHD events occurred in the 0–5% risk group which made up 47% of the study population. The 5–10% group had event rates (13.7%) greater than the study average (12.2%), especially in those with thicker CIMT (>75
th
percentile, event rate 17%), and greater event rates than those in the 0–5% risk group (4.1%) (table

). Given the notably higher observed CHD risk in the 5–10% group (especially in those with thicker CIMT) relative to the 0–5% group, the availability of safe, low cost lipid lowering medications and low risk tests such as ultrasound that may improve risk stratification, it may be time to evaluate the low risk group more carefully for cardiovascular preventive therapies.

Table.

Incident CHD in the various risk groups over a mean follow up of 13.8 years in the ARIC study
Abstract 4990: Multi-Marker Approach Using Novel Biomarkers Improves Prediction of Subclinical Atherosclerosis: Observations from the Dallas Heart Study
Authors: Rohatgi Anand , Matulevicius Susan , Das Sandeep R , Khera Amit , McGuire Darren K , Ayers Colby R , de Lemos James A
Published: July 2021

Background: Although many novel markers are independently associated with cardiovascular risk, few significantly improve predictive performance. We hypothesized that combining multiple novel biomarkers would improve prediction of subclinical atherosclerosis over standard methods.

Methods: We measured coronary calcium (CAC) by electron beam CT (n=2440), as well as hsCRP, NT-proBNP, and four novel biomarkers including soluble receptor for advanced glycation end products (sRAGE), peptidoglycan recognition protein-1 (PGLYRP-1), soluble endothelial cell-selective adhesion molecule (sESAM), and osteoprotegerin (OPG) in the Dallas Heart Study, a multi-ethnic probability-based population sample age 30 – 65. An integer score was created based on the number of biomarkers that were elevated >= 95th percentile for sex and race. The incremental value of the biomarker score over a model including Framingham risk categories in predicting CAC was analyzed.

Results: Increasing biomarker score was associated with increased CAC prevalence (59% for score >= 3 vs. 17% for score = 0, figure

). Compared with the Framingham risk model alone, the addition of the biomarker score significantly increased the C index (0.705 vs. 0.749, p<0.0001), lowered the Bayesian Information Criterion (2232 vs. 2195), and also improved reclassification into higher and lower risk categories (Net Reclassification Index = 14.2%, p<0.0001; Integrated Discrimination Index =2.4%, p<0.0001).

Conclusion: Use of a multi-marker score including established and novel biomarkers improves prediction of CAC beyond the Framingham risk categories using multiple different statistical metrics.

Figure.

Prevalence of CAC by Biomarker Score*
Abstract 4996: Six-year Trends in Low-Density Lipoprotein Cholesterol Goal Achievement in High-Risk United States Residents: National Health and Nutrition Examination Survey, 1999 to 2004
Authors: Karmali Kunal N , Tattersall Matthew C , Cullen Michael W , Keevil Jon G
Published: July 2021

Background
: In 2001, the Adult Treatment Panel III guidelines expanded the definition of high risk by including coronary heart disease (CHD) risk equivalent conditions. Low-density lipoprotein cholesterol (LDL-C) goals for all high-risk patients were intensified to < 100 mg/dL. This study investigates the size of the high-risk U.S. population with and without CHD and the percent LDL-C goal achievement across six years.

Methods
: Data from three National Health and Nutrition Examination Surveys: 1999–2000, 2001–2002, and 2003–2004 were analyzed to identify U.S. residents at high risk per ATP III guidelines. The size of each survey’s high-risk cohort and percentage LDL-C goal achievement was stratified by presence of CHD or CHD risk equivalent conditions.

Results
: Across the three surveys, the high-risk population was 22.2, 23.8 and 28.0 million. The percentage of all high-risk individuals with LDL-C < 100 mg/dL was 22.9%, 31.5% and 32.9%. Goal achievement in those without CHD was 20.2%, 26.0% and 31.5%. In CHD patients, goal achievement increased from 27.0% (1999–2000) to 40.9% (2001–2002) but then dropped to 35.1% (2003–2004).

Conclusions
: Across six years from 1999 to 2004, U.S. residents at high risk increased by 26.2% (5.8 million) compared to a 5.2% (8.3 million) rise in eligible population. Improvement in LDL-C goal achievement for those without CHD was consistent across the three surveys. Those with CHD also had a robust improvement from 1999–2000 to 2001–2002. However, while a greater absolute number of those with CHD met goal in 2003–2004, the percentage was reduced. This suggests a need for renewed attention to LDL-C goal achievement in individuals with CHD.

High Risk Cholesterol Goal Achievement by CHD status
Abstract 5005: Development and Testing of a Risk Prediction Algorithm for Incident Hypertension in Women with Currently Normal Blood Pressure
Authors: Paynter Nina P , Cook Nancy R , Everett Brendan M , Sesso Howard D , Buring Julie E , Ridker Paul M
Published: July 2021

Background
: We sought to determine whether a hypertension risk prediction model based on patient characteristics and blood biomarkers might improve upon risk prediction based on current blood pressure alone.

Methods
: A prospective cohort of 14,822 normotensive women were followed over 8 years for the development of hypertension. Among a randomly selected two-thirds sample (“development cohort”; N=9,427), hypertension prediction models were developed using 52 potential predictors and compared to a model based on blood pressure alone. Each prediction model was validated in the remaining one-third sample (“validation cohort”; N=5,395).

Results
: In the development cohort, the best prediction model for incident hypertension included age, blood pressure, ethnicity, body mass index, total grain intake, apolipoprotein B, lipoprotein(a), and C-reactive protein. While this model was superior to a model based on blood pressure alone. it was only marginally better than a simplified model including age, blood pressure, ethnicity, and body mass index. In the validation cohort, the best model was no longer calibrated. The simplified model, however, demonstrated adequate calibration in the validation cohort (Hosmer-Lemeshow P-value 0.14), with a c-index similar to that of the best model (0.703 vs 0.705), and when compared to the model based on blood pressure alone (Table

), reclassified 1499 participants to hypertension risk categories that were closer to the observed risk in all but one instance.

Conclusion
: In this prospective cohort of initially normotensive women, a model based on readily available clinical information predicted incident hypertension better than a model based on blood pressure alone and, unlike more complex models using blood biomarkers, remained calibrated in the validation cohort.

Reclassification of Predicted 8-Year Hypertension Risk Categories
Abstract 5011: Role of Autonomic Nervous System Dysregulation and Inflammation in the Increased Risk of Depression for Cardiovascular Mortality: The Cardiovascular Health Study
Authors: Kop Willem J , Stein Phyllis K , Barzilay Joshua I , Tracy Russell P , Gottdiener John S
Published: July 2021

The increased cardiovascular (CV) risk associated with depression is hypothesized to be explained by autonomic nervous system (ANS) dysregulation and inflammatory processes. This study determines the role of ANS dysregulation and inflammation in the predictive value of depression for CV mortality. 908 participants of the Cardiovascular Health Study (age 71±5 yrs) free of CV disease were evaluated for depression (CES-D scale), ANS dysregulation by abnormal non-linear heart rate variability (decreased short-term fractal scaling exponent), and inflammation (IL-6, CRP, fibrinogen and WBC). Predictors of CV mortality were examined using Cox regression analysis, adjusting for age, sex, race, systolic blood pressure, diabetes, subclinical disease, use of beta-blockers, smoking status, BMI, and physical activity (median follow-up=13.3 yrs). Risks were calculated for subgroups based on the presence or absence of depression, and ANS or inflammatory CV risk factors (Figure

). Depression was predictive of CV mortality (RR=1.88, CI=1.23–2.86), ANS dysregulation (p=0.014) and inflammatory markers (IL-6 p=0.072; WBC p=0.033; and fibrinogen p=0.050) were correlated with depression. The association of depression with CV mortality occurred primarily in the presence of ANS dysregulation and/or inflammation (Figure

). Addition of ANS and inflammatory markers to the multivariate model did not substantially reduce the CV mortality risk of depression (adjusted RR=1.65, CI=1.03–2.65). Depression is predictive of cardiovascular mortality, and the elevated risk is additive to autonomic nervous system dysregulation and inflammation
Abstract 5051: Alteration of Atherogenic Lipoproteins by Statin Therapy in Patients With Diabetes in a Large Pooled Clinical Trial Database
Authors: Ballantyne Christie M , Barter Philip J , Nicholls Stephen J , Cain Valerie A , Raichlen Joel S
Published: July 2021

Reducing LDL-C to current goals may still leave an excess of atherogenic lipoproteins as reflected in apolipoprotein (Apo) B levels. Apo B provides a measure of atherogenic particles in blood, a predictor of CHD events. Patients with diabetes mellitus (DM) are at increased CHD risk and warrant intensive therapy. Recent joint ADA and ACCF guidelines recommend reducing Apo B to <90 mg/dL in high-risk patients and optionally to <80 mg/dL in those at very high risk. We examined the effect of statin therapy on the relationship between these Apo B targets and LDL-C and non-high-density lipoprotein cholesterol (non-HDL-C) in high-risk patients with and without DM. A pooled analysis of data in the rosuvastatin clinical development program was used to identify 12,269 high CHD risk patients who were examined at baseline and after therapy with rosuvastatin, atorvastatin or simvastatin. Apo B was compared with LDL-C and non-HDL-C both at baseline and on therapy using linear regression. At baseline, Apo B target of 90 mg/dL in DM was equivalent to LDL-C of 115 mg/dL and non-HDL-C of 139.8 mg/dL, which was slightly higher than for non-DM (Table

). Achieving Apo B of 90 mg/dL or 80 mg/dL required much more aggressive LDL-C and non-HDL-C goals on statin therapy. Of note, this effect and resultant targets were very similar in DM and non-DM. Achieving with statin therapy Apo B of 90 mg/dL in high-risk patients requires LDL-C target of ~80 mg/dL and non-HDL-C target of ~108 mg/dL. The on-therapy LDL-C target (<70 mg/dL) and non-HDL-C target (<100 mg/dL) for very high risk patients correspond to Apo B target of 80 mg/dL. During statin therapy, Apo B correlated well with LDL-C (R
2
=0.77– 0.81) and very well with non-HDL-C (R
2
=0.88 – 0.90). Non-HDL-C may be a useful surrogate for direct Apo B measurement. High-risk DM and non-DM patients require lower LDL-C and non-HDL-C targets during statin therapy in order to reduce Apo B to the recommended level.
Abstract 5055: The SANDS Trial: Does Aggressive Lowering of LDL-C and Non-HDL-C in Diabetes Decrease the Plasma ApoB and LDL-C Particle Number?
Authors: Howard Barbara V , Devereux Richard B , Fleg Jerome L , Howard Wm. James , Mete Mihriye , Otvos James D , Ratner Robert E , Roman Mary J , Russell Marie , Umans Jason G , Weissman Neil J
Published: July 2021

Background:
Concern has been raised that aggressive lowering of LDL-C may not be accompanied by reductions in particle number or apoB lipoprotein concentrations. The SANDS trial demonstrated that a group treated for 3 years to aggressive (AGG) targets of LDL-C ≤ 70 mg/dL and non-HDL-C ≤ 100 mg/dL had a decrease in atherosclerosis, as measured by regression of carotid intimal medial thickness (CIMT) and decreased mean arterial mass, compared with a standard group (STD) treated to LDL-C and non-HDL-C of 100 and 130 mg/dL, respectively.

Methods:
Participants were 499 type 2 diabetic men and women (average age 56 y) with no previous CVD events; 426 had all baseline and 36-mo lipoprotein variables. Mean baseline BMI (33kg/m
2
), A1c (8.0%), and HDL-C (46mg/dl) did not change during the study. A standardized algorithm for lipid lowering was used in both groups; the number of hypolipidemic drugs (mean [SD]) was 1.5 [.75] and 1.2 [.73] in the AGG and STD groups, respectively. At baseline and 36 months, lipoprotein particle number (LDL-P and VLDL-P) was quantified by nuclear magnetic resonance, and plasma apoB by immunoassay.

Results:
There were significant decreases in apoB, LDL-P, VLDL-P, and VLDL size but not LDL size in the AGG vs STD groups. The decrease in LDL-P was reflected in all LDL fractions. In an ordered logit analyses, the probability of a decrease in CIMT was significantly related to decrease in LDL-C and separately to non-HDL-C (p <.005), but not significantly related to the decrease in apoB (p =.19) and LDL-P (p =.055).

Conclusion:
Aggressively lowering LDL-C and non-HDL-C to targets of 70 and 100 mg/dL, respectively, was accompanied by a significant decrease in LDL-P and VLDL-P and a decline in total plasma apoB; changes in LDL-C and non-HDL-C were separately the best predictors of IMT decrease. The relationship of the associated decrease in carotid atherosclerosis to CVD events awaits longer term observation.
Abstract 5063: Cardiovascular Effects of Transdermal Testosterone in Postmenopausal Women
Authors: Vitale C , Collins P , Marazzi G , Caminiti G , Lodhi I , Rodenberg C A , Rosano G M
Published: July 2021

Testosterone Transdermal Patch (TTP) has been developed for the treatment of postmeno-pausal women (PMW) with hypoactive sexual desire disorder (HSDD). Since the cardiovascular (CV) effects of testosterone in women are still unclear we conducted a pooled analysis of the large phase III clinical program to evaluate the efficacy and safety of 300 μg/day TTP, alone or in association with hormone replacement therapy (HRT), versus placebo in surgical or natural PMW.

Design & Methods: A total of 2795 women aged between 26 –70 years (mean age 52(SD=6.8) years) were included in 5 phase III randomized, double-blind, placebo-controlled clinical trials (treatment duration range 24 – 52 weeks) as part of the TTP Clinical program. 4 studies included PMW (natural and surgical, two each respectively) receiving HRT while 1 study was conducted without HRT, in either surgical or natural PMW. Women with known CV disorders were excluded from the studies. Changes from baseline in standard metabolic and CV risk factors were compared. The incidence of stroke, myocardial infarction (MI) and venous thromboembolism (VTE) alone or as a composite CV endpoint was assessed.

Results: The 2795 PMW were randomized to receive either placebo (n=1297) or TTP (n=1498). Baseline mean BMI was 27 kg/m2 (SD=5.3 kg/m2) and 56% were naturally menopausal. The demographic and baseline parameters were similar among the treatment groups. No significant changes in CV risk factors (Total Cholesterol, Triglycerides, Insulin, Glucose, Systolic and Diastolic Blood Pressure) were detected during the study period, apart from a blunting of the increases in HDL-C by TTP at 24 and 52 weeks (Placebo 52-week mean change 2.59 mg/dl vs. TTP 52-week mean change 1.20 mg/dl, p<0.005) and of the decrease in LDL-C by TTP at 24 (p<0.05), but not at 52 weeks. During the double-blind (24 weeks), placebo-controlled period of the combined studies, 4 major CV events (2 MIs and 2 strokes) were reported in placebo patients and 3 (2 MIs and 1 stroke) in those receiving TTP. One VTE occurred in a patient receiving TTP and HRT.

Conclusion: TTP therapy in these clinical trials did not adversely affect CV risk profile and did not change the risk of major CV events in these surgical and naturally PMW with or without concomitant HRT.
Abstract 5066: The Treatment Effect of Perindopril is Consistent in All Patients with Vascular Disease or High Risk of Vascular Disease: A Combined Analysis of Three Perindopril Trials
Authors: Brugts Jasper J , Boersma Eric , Deckers Jaap W , Remme Willem , Bertrand Michel , Fox Kim , Ferrari Roberto , Simoons Maarten L
Published: July 2021

The beneficial effect of the ACE-inhibitor perindopril has been demonstrated in large placebo-controlled clinical trials consisting of patients with stable CAD without overt heart failure (EUROPA), history of stroke (PROGRESS) and diabetes mellitus (ADVANCE). EUROPA investigated the effect of perindopril 8 mg during a mean follow-up of 4.2 years. PROGRESS investigated a perindopril 4mg/indapamide regimen during 4 years of follow-up and ADVANCE studied a perindopril 4 mg/indapamide regimen during 4.3 years of follow-up. In the three trials, mean blood pressure reduction was respectively, 5/2 mmHg, 9/4 mmHg and 6/2 mmHg. In all three trials, perindopril significantly reduced major cardiovascular events independent of baseline blood pressure levels. For this meta-analysis, we analyzed the treatment effect of the three trials combined on the shared endpoints of all-cause mortality and cardiovascular mortality & MI. Table 1

shows an analysis of three perindopril trials (EUROPA, PROGRESS and ADVANCE). When these findings were combined (n=29493), perindopril significantly reduced all-cause mortality (OR 0.89, 95% CI 0.82– 0.97), and cardiovascular mortality, MI (OR 0.82, 95% CI 0.74 – 0.90). This combined analysis shows that perindopril reduced cardiovascular events by 11–18% irrespective of risk level or the type of patients, which is in line with prior meta-analyses and risk models. This treatment benefit by perindopril is consistent among all patients with vascular disease or high risk of vascular disease.

The treatment benefit by perindopril among patients with vascular disease or high-risk vascular disease.
Abstract 5083: Body Composition, Cardiorespiratory Fitness and Low-Grade Inflammation in Middle-Aged Men and Women
Authors: Arsenault Benoit J , Cartier Amelie , Cote Melanie , Lemieux Isabelle , Tremblay Angelo , Bouchard Claude , Perusse Louis , Despres Jean-Pierre
Published: July 2021

Background:
Although low levels of cardiorespiratory fitness (CRF) and obesity are often associated with a deteriorated cardiometabolic risk profile including low-grade inflammation, the respective contributions of specific indices of body fat distribution and CRF to variation of inflammatory markers remains uncertain. We therefore sought to determine the respective contributions of visceral adipose tissue (VAT) accumulation and CRF to variation of inflammatory markers in middle-aged men and women.

Methods and Results:
A complete lipoprotein-lipid profile and circulating levels of inflammatory markers such as C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and adiponectin were obtained and in a sample of healthy men (n=120) and women (n=152) covering a wide range of obesity values. VAT accumulation was measured by computed tomography and CRF levels were measured by a progressive submaximal physical working capacity test. In both men and women, VAT was positively associated with CRP and IL-6 levels (r≥0.35, p<0.0001), negatively associated with adiponectin (r≤ −0.29, p≤0.0003), after adjusting for CRF. After adjusting for VAT, CRF was not associated with variation in inflammatory markers in women and only with adiponectin in men (r= −0.20, p=0.03). An inflammation score was developed based on the sex-specific 50
th
percentile values of each inflammatory marker (0 or 1) which yielded a score ranging from 0 (low) to 4 (high). Participants who scored 0, 1 or 2 were considered as having a low score and participants who scored 3 or 4 had an elevated inflammation score. In participants with low VAT (<130cm
2
for men and <100cm
2
for women), the prevalence of participants with an elevated inflammation score was of 23.9% and of 28.0%, respectively for participants with high and low CRF, whereas in participants with an elevated VAT accumulation, the prevalence of an elevated inflammation score was of 60.0% and of 61.7%, respectively for high and low CRF.

Conclusions:
These results suggest that the inflammatory state associated with low CRF is largely attributable to the increased VAT accumulation often observed in poorly fit individuals.
Abstract 5093: Genetically Elevated Lipoprotein(a) and Risk of Myocardial Infarction - a Positive Mendelian Randomization Study
Authors: Kamstrup Pia , Tybjærg-Hansen Anne , Steffensen Rolf , Nordestgaard Børge G
Published: July 2021

Background:
High levels of lipoprotein(a) (Lp(a)) associate with increased risk of myocardial infarction (MI). We tested whether this is a causal effect using a Mendelian randomization design.

Methods:
We genotyped for the Lp(a) kringle IV type 2 (KIV-2) size polymorphism, which explains 21% of variation in plasma levels of Lp(a). We used a cohort study of the Danish general population, The Copenhagen City Heart Study, including 9867 individuals followed for up to 16 years during which time 599 developed MI, and a case-control study, The Copenhagen Ischemic Heart Disease Study, including 1118 MI patients and 2234 controls.

Results:
First, increased plasma levels of Lp(a) associated with increased risk of MI (Lp(a) tertiles, trend: p<0.001). Second, number of KIV-2 repeats inversely associated with Lp(a) levels: mean Lp(a) levels were 56, 31, 20, and 15 mg/dL for the 1
st
, 2
nd
, 3
rd
, and 4
th
quartile of KIV-2 repeats, respectively (trend, p<0.001, Figure

). Third, multifactorially adjusted hazard ratios for MI were 1.6(95% CI:1.3–.2.0), 1.3(1.0 –1.7), and 1.1(0.9 –1.4) for individuals in the 1
st
, 2
nd
, and 3
rd
quartile, respectively, as compared to individuals in the 4
th
quartile of KIV-2 repeats (Figure

). Finally, in the case-control study, multifactorially adjusted odds ratios for MI were 1.5(1.2–1.9), 1.3(1.0 –1.6), and 1.2(1.0 –1.5) for individuals in the 1
st
, 2
nd
, and 3
rd
quartile, respectively, as compared to individuals in the 4
th
quartile of KIV-2 repeats.

Conclusion:
Since Lp(a) levels predict MI, and since Lp(a) KIV-2 genotype predicts both life-long increased Lp(a) levels and MI, increased Lp(a) levels appear to directly cause MI.

Figure.

Levels of lipoprotein (a) and risk of myocardial infarction by KIV-2
Abstract 5095: Association of Genetic Variation in the IL-1 Gene with Diabetes and Glucose Homeostasis
Authors: Luotola Kari , Pääkkönen Rauni , Alanne Mervi , Lanki Timo , Peters Annette , Jula Antti , Perola Markus , Salomaa Veikko
Published: July 2021

To examine the associations of genetic variation in the interleukin 1 (IL-1) cluster with diabetes and glucose homeostasis. We determined 15 single nucleotide polymorphisms in the IL-1α, IL-1β and IL-1 receptor antagonist (IL1RN) genes in a Finnish population sample of 6,771 individuals. Fasting glucose and insulin were determined from all participants. Indices of insulin resistance and beta cell function were calculated using the homeostasis model assessment (HOMA-IR and HOMA-β cell). Two-hour oral glucose tolerance tests (OGTT) with insulin and glucose measurements at 30 min and 120 min were carried out on a subsample of 1,390 participants. Replication of the findings on prevalent diabetes was tested in another independent material of 972 European myocardial infarction (MI) survivors (AIRGENE). Replication of the associations with fasting insulin, glucose and HOMA-IR was searched from the publicly available Framingham SNP Health Association Resource (SHARe) database. In multivariate models haplotypic variation in the IL-1β SNPs rs1143634, rs3917356 and rs16944 was associated with prevalent diabetes among Health 2000 participants: rate ratio (RR) 1.54 (95% CI 1.03–2.30, p=0.037), comparing participants with two copies of the ACG haplotype with participants with no copy of the haplotype. This association was replicated among the European MI survivors: RR 2.09 (1.17–3.76, p=0.013). The same haplotype was associated with HOMA-IR (p=0.007), fasting insulin (p=0.021) and in the OGTT subsample with area under the glucose curve (AUC glucose) (p=0.0002). Rs1143634 was the tagging SNP of this haplotype and showed associations consistent with the haplotypic analyses. In the Framingham SNP Health Association Resource (SHARe) genome-wide data rs1374284 of the IL-1β gene is associated with fasting insulin and HOMA-IR (p=3.56e-4 and p=1.51e-4, respectively). Rs1374284 is in high LD with the rs1143634 (r2>0.80) most probably reflecting the same signal as observed in our study. Genetic variation in the IL-1 cluster is associated with prevalent diabetes and several measures of glucose homeostasis. The associations seem consistent in several populations of white European ancestry.
Abstract 5133: Does Public Smoking Ban Reduce the Incidence of Myocardial Infarction in Michigan? A Systematic Review and Attributable Risk Analysis
Authors: Al-Mallah Mouaz , Alqaisi Fadi , Nerenz David , Boedeker Stephanie , Weaver W. Douglas
Published: July 2021

Background: Smoking is a well-established risk factor for cardiovascular disease. The Michigan legislature is currently considering a proposal for a comprehensive smoking ban (CSB) in Michigan. The potential impact of such a law on the incidence AMI is not known. We conducted a meta-analysis to study the impact of CSB on the incidence of AMI and calculated the impact of potential CSB on the incidence of AMI in Michigan.

Methods: We searched MEDLINE, EMBASE, and Cochrane databases from inception till May 2008 for studies comparing the rates of AMI hospital admissions before and in the year after the implementation of CSB legislation. Of 135 potentially relevant articles screened initially, 5 studies met the inclusion criteria. A random-effects model meta-analysis was done and between-studies heterogeneity was compared with I2. The attributable risk (AR) of CSB on AMI incidence was calculated and multiplied with the number of AMI admissions in Michigan.

Results: In the published studies, a CSB was associated with a decrease in the incidence of AMI (RR 96%, 95% CI 93%–100%, p=0.05). There was no heterogeneity between the included studies (I2<50%). The AR of CSB on the incidence of AMI is −4.2%. The average number of hospital admissions for AMI as first-listed diagnosis in Michigan between 1999 and 2006 was 27,007 per year. Thus, if a CSB legislation is implemented in Michigan in 2008, the calculated reduction of hospital admissions for AMI is 1130 admissions per year as of 2009..

Conclusion: CSB is associated with a significant reduction of annual hospital admissions for AMI. The financial impact of this reduction on health care cost is yet to be determined.
Abstract 5137: Normalization of Visceral Adiposity is a Better Therapeutic Target Than Normalisation of Body Weight: Evidence From the Synergie Trial
Authors: Cote Melanie , Cartier Amelie , Poirier Paul , Mauriege Pascale , Bergeron Jean , Almeras Natalie , Tremblay Angelo , Lemieux Isabelle , Despres Jean-Pierre
Published: July 2021

A moderate weight loss of 5 to 10% has been shown to induce several improvements in the cardiometabolic profile of high risk obese patients and is therefore generally recommended as a clinically meaningful therapeutic target. The SYNERGIE study is a lifestyle modification program which aims at reshaping the nutritional and physical activity habits of sedentary men with visceral obesity. In the present analyses, 101 healthy men aged 30 to 65 years without diabetes but characterized by visceral obesity and by the high triglyceride-low HDL cholesterol atherogenic dyslipidemia were assigned to a personalized nutritional and physical activity management program which included a monthly visit. In response to the intervention program, men of the study decreased their body weight, waist circumference (Δ=−9 cm, p<0.0001) and their visceral adipose tissue (VAT) (Δ=−79 cm
2
, p<0.0001). The intervention program also significantly improved several metabolic parameters such as HDL cholesterol (Δ=+0.13 mmol/l, p<0.0001) and triglycerides levels (Δ =−0.6 mmol/l, p<0.0001) as well as glucose and insulin homeostasis variables. However, when compared to a control group of healthy nonobese men (mean BMI=24 kg/m
2
, n=65), men of the intervention group did not fully normalize their cardiometabolic profile after 1-year. In order to further explore this issue, men of the intervention group were classified into quartiles of VAT accumulation achieved after 1-year. In comparison with men in the top VAT quartile, men in the lowest VAT quartile had markedly improved cardiometabolic profile. Moreover, when compared to nonobese controls, men who reached low levels of VAT were characterized by a lower VAT accumulation (100 cm vs. 124 cm) despite higher body weight (80 kg vs. 73 kg) and body mass index (27 kg/m
2
vs. 24 kg/m
2
) than healthy nonobese controls. These men were also characterized by “normalized” HDL cholesterol (1.17 mmol/l), triglycerides (1.58 mmol/l), glucose (5.8 mmol/l), apolipoprotein B (0.97 mg/dl) and apolipoprotein AI (1.35 g/l) compared to nonobese controls. These results suggest that VAT may represent a better therapeutic target than the normalisation of body weight in the management of cardiometabolic risk in high risk abdominally obese men.
Abstract 5144: Extended-Release Niacin Reduces LDL-C Particle Number Even In The Absence Of Changes In Total LDL-C Levels
Authors: Jafri Haseeb , Kuvin Jeffrey T , Alsheikh-Ali Alawi A , Mooney Paula , Kimmelstiel Carey D , Karas Richard H
Published: July 2021

Introduction:
The importance of the number of circulating low-density lipoprotein cholesterol (LDL-C) particles, in addition to the total level of LDL-C is increasingly recognized. The effects of Extended Release Niacin (ERN) on LDL-C particle number have not been studied. The primary objective of this study was to evaluate ERN’s effects on LDL-C particle number. ERN’s effect on high-density lipoprotein cholesterol (HDL-C) particle number was a secondary objective.

Hypothesis
: In patients with stable coronary artery disease (CAD) and LDL-C at goal, the addition of ERN will favorably alter LDL-C particle number.

Methods:
60 patients with stable CAD and well-controlled LDL-C levels were randomly assigned to 3 months of ERN (1g/d) or placebo in addition to their baseline medications. Particle number was analyzed by proton nuclear magnetic resonance spectroscopy at baseline and after 3 months.

Results:
Baseline and follow up lipid values are shown in

Table

. Compared to baseline, while ERN had no significant effect on total LDL-C levels, it significantly decreased the mean number of medium and small very small LDL-C particles (p=0.005). The percent change in each of these particle numbers was significantly greater in the ERN group compared to placebo as well (p<0.05 for each) ERN therapy raised HDL-C levels and also significantly shifted from small to large HDL-C particles (p<0.001). There were no significant changes in lipid values or particle numbers in the placebo-treated patients (

Table

).

Conclusion:
In patients with stable CAD and well-controlled LDL-C levels, ERN significantly reduced the number of circulating particles of the more atherogenic subtypes of LDL-C, despite having no effect on total LDL-C levels. ERN also favorably altered particle numbers of HDL-C. These findings suggest that ERN-induced alterations in particle number may contribute to its anti-atherosclerotic effects, and that these effects may not be evident from the standard lipid profile.
Abstract 5149: Statin Use and Risk of Developing Type 2 Diabetes: A Meta-Analysis
Authors: Rajpathak Swapnil , Kumbhani Dharam J , Crandall Jill P
Published: July 2021

Background
: The beneficial effects of statin therapy may extend well beyond its cholesterol-lowering properties. Such ‘pleiotropic’ effects of statins may include reducing systemic inflammation, improving endothelial function and lowering cellular oxidative stress. Since these mechanisms are implicated in the pathogenesis of type 2 diabetes, statin therapy may, therefore, potentially reduce the risk of developing diabetes.

Methods
: We conducted a meta-analysis of randomized controlled clinical trials (RCTs) that evaluated the effect of statin therapy on the incidence of type 2 diabetes. Effect estimates were calculated using a random effects model.

Results
: We identified 5 clinical trials of statin treatment that reported incident diabetes, which included 42,860 patients without preexisting diabetes. Intervention in these trials included four different statins with a dose range of 10 to 40 mg/d. There was a significant heterogeneity between the studies in terms of ascertainment of diabetes, which was not the primary outcome in these RCTs. We found no difference between the incidence of type 2 diabetes among patients randomized to statins (3.6%) compared to placebo (3.4%) during an average (weighted mean) follow-up of 47.2 months (Relative Risk: 1.05; 95% confidence intervals: 0.95–1.16; p=0.36). The results were similar when stratified by age or specific statin used.

Conclusion
: Current evidence from RCTs does not support a beneficial effect of statin therapy on the risk of developing type 2 diabetes. RCTs of statin therapy with diabetes as a primary outcome are required to definitively determine the role of statins in the primary prevention of diabetes.