Elevated Cardiovascular Risk Factors Research Articles

A PHASE 1 FIRST-IN-HUMAN STUDY OF THE MCL-1 INHIBITOR AZD5991 IN PATIENTS WITH RELAPSED/REFRACTORY HEMATOLOGIC MALIGNANCIES.

AZD5991, a human MCL-1 inhibitor, was assessed for safety, tolerability, pharmacokinetics (PK), and antitumor activity as monotherapy and in combination with venetoclax in patients with relapsed or refractory (R/R) hematologic malignancies. In the monotherapy cohort (n=61), patients with hematologic malignancies received AZD5991 intravenously in escalating doses either once or twice weekly, following intrapatient dose escalation, on a 3-week cycle. In the combination cohort (n=17), patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) received escalating doses of AZD5991 and venetoclax on either a 3-week or 4-week cycle. Primary objectives were safety and maximum tolerated dose; secondary objectives included plasma PK and antitumor activity. The most common (≥30%) adverse events (AEs) were diarrhea (59.0%), nausea (55.1%), and vomiting (47.4%). Four deaths occurred due to AEs: cardiac arrest, sepsis, tumor lysis syndrome (TLS), and acute respiratory failure; only TLS was related to AZD5991. Dose-limiting toxicities occurred in 5 patients. Three patients with MDS achieved an objective response: 1 marrow complete remission (mCR) without hematologic improvement, 1 partial remission with AZD5991 monotherapy, and 1 mCR with AZD5991+venetoclax. Asymptomatic elevations of troponin I or T were observed in 8 (10.3%) patients. Post hoc retrospective analysis revealed elevated troponin T in 14/31 patients before any AZD5991 dose and in 54/65 patients after any AZD5991 dose at or after cycle 1. There were no associations between elevated troponin and cardiovascular risk factors. Treatment with AZD5991 was associated with high incidence of laboratory troponin elevation and a low overall response rate.

BENEFICIAL ROLE OF DIETARY CHANGES IN MENOPAUSE: IMPACT ON CARDIOVASCULAR RISK

Objective: The changing hormonal milieu in post-menopausal women (PMW) predisposes them to increase cardiovascular (CV) risk, due to a constellation of risk factors, such as visceral obesity, atherogenic dyslipidemia and arterial hypertension. Our ongoing study aims to evaluate the impact of dietary changes in CV risk in PMW. Design and method: For 1 year, 65 PMW with BMI 24-39 Kg/m2 and at least another CV risk factor were followed. Anthropometric parameters, plicometry and blood pressure (BP) were taken. Questionnaires on medical history, physical activity, and food frequency (FFQ) were administered. Balanced low-calorie dietary plan with quantitative advice were released. Repeated measures ANOVA at 1 year were performed. Results: We observed at 1 year significant reductions (p<0.01) in weight (δ=-4.5 Kg), BMI (δ=-1.7 Kg/m2), waist (δ=-4.3cm) and hips (δ=-3.1cm) circumferences, subscapular (δ=-5.8mm), suprailiac (δ=-3.3mm) and triceps (δ=-5.5mm) skinfolds, adipose area of the arm (AFA) (δ=-7.3cm2), and fat mass (δ=-4.5kg) without variation of the lean mass (δ=-0.1 kg, p=0.48). All those reductions were followed by change in the obesity prevalence (-21.1%), in the fat mass distribution with 10% reduction in abdominal and truncular obesity and 5.2% reduction on waist-to-height ratio, and in systolic (δ=-8.8 mmHg) and diastolic (δ=-4.3 mmHg) BP. Significant positive correlations (p<0.0001) were observed between weight reduction and the following variables: waist (r=0.61) and hip (r=0.77) circumferences, subscapularis (r=0.56) and triceps (r=0.66) skinfolds, and AFA (r=0.73). Significant reductions (p<0.05) were observed in daily caloric intake (δ=-99.8Kcal/day), due to the reduction in fat intake (36.6->33.6%), specially saturated fatty acids (12->10.8%) and cholesterol (δ=-23.1mg/day), with maintenance of the average level of physical activity and in agreement with a significant reductions in consumption of animal meats, visible fat, processed meats, olive oil, sweets and baked goods detected by FFQ. Conclusions: The study underlines the medium-term utility of a 1 year balanced low-calorie diet in PMW with elevated CV risk factors with a clear reduction in CV risk.

Abstract MP06: Cardiovascular Disease in Community-Dwelling US Adults Involved With the Criminal Justice System: A Simulation Analysis

Introduction: Approximately 4.4 million US adults live in the community while on probation or parole. They have disproportionately elevated cardiovascular risk factors, morbidity and mortality, along with limited access to healthcare. However, the long-term burden of cardiovascular disease (CVD) in this population is uncertain. We developed a simulation model to quantify cardiovascular risk and adverse events in community-dwelling US adults involved with the criminal justice system, leveraging all known sources of data on this under-studied, high-risk population. Methods: We adapted the CVD Policy Model, a validated state-transition simulation model of CVD in all US adults, using input data specific to 25-54 year-old individuals on probation or parole in 2018. Population size was defined using estimates from the Bureau of Justice Statistics. CVD risk factor burden was approximated by re-weighting data from the National Health and Nutrition Examination Survey years 2005 to 2018 to match demographic, socioeconomic, and health variables among individuals reporting past-year probation or parole in the National Survey on Drug Use and Health. CVD incidence and mortality rates were calibrated to outcomes in cohort studies and vital statistics data. Outcomes were myocardial infarction (MI), stroke, and death over a 10-year horizon (2018-2027) and were compared with projections for an age- and gender-matched cohort of adults in the general US population. We also examined projected reductions in CVD outcomes over 10 years that could be expected if risk factor distributions in the probation/parole population were similar to distributions observed for the general US population. Results: The simulated cohort consisted of 2.9 million adults 25-54 years of age on probation or parole in 2018; 71% were men, 30% were living below the poverty line, and 57% had no regular access to healthcare. An estimated 61% were current smokers, 29% had BP ≥130/80 mmHg, and 8% had diabetes. The study cohort was projected to experience between 36,400 and 69,600 incident MIs and between 22,400 and 37,500 incident strokes over 10 years. This would be 1.4-2.6 times the CVD incidence in age- and gender-matched adults in the general US population. Lowering rates of active smoking in those on probation or parole to rates observed for the general US population (i.e., from 61% to 21%) would reduce MI and stroke events by 16,400 to 29,100 over 10 years, a 27% reduction from current projections. Discussion: We developed and calibrated a computer simulation model to quantify the burden of CVD in community-dwelling US adults followed by the US justice system. We project that adults on probation or parole have higher CVD risk than the general US population. Future work will leverage this platform to estimate the impact of clinical, community, and policy interventions to reduce CVD burden in this vulnerable population.

Cardiac autonomic function is preserved in young adults with major depressive disorder.

The prevalence of major depressive disorder (MDD) is highest in young adults and contributes to an increased risk of developing future cardiovascular disease (CVD). However, the underlying mechanisms remain unclear. The studies examining cardiac autonomic function that have included young unmedicated adults with MDD report equivocal findings, and few have considered the potential influence of disease severity or duration. We hypothesized that heart rate variability (HRV) and cardiac baroreflex sensitivity (BRS) would be reduced in young unmedicated adults with MDD (18-30 yr old) compared with healthy nondepressed young adults (HA). We further hypothesized that greater symptom severity would be related to poorer cardiac autonomic function in young adults with MDD. Heart rate and beat-to-beat blood pressure were continuously recorded during 10 min of supine rest to assess HRV and cardiac BRS in 28 HA (17 female, 22 ± 3 yr old) and 37 adults with MDD experiencing current symptoms of mild-to-moderate severity (unmedicated; 28 female, 20 ± 3 yr old). Neither HRV [root mean square of successive differences between normal heartbeats (RMSSD): 63 ± 34 HA vs. 79 ± 36 ms MDD; P = 0.14] nor cardiac BRS (overall gain, 21 ± 10 HA vs. 23 ± 7 ms/mmHg MDD; P = 0.59) were different between groups. In young adults with MDD, there was no association between current depressive symptom severity and either HRV (RMSSD, R2 = 0.004, P = 0.73) or cardiac BRS (overall gain, R2 = 0.02, P = 0.85). Taken together, these data suggest that cardiac autonomic dysfunction may not contribute to elevated cardiovascular risk factor profiles in young unmedicated adults with MDD of mild-to-moderate severity.NEW & NOTEWORTHY This study investigated cardiac autonomic function in young unmedicated adults with major depressive disorder (MDD). The results demonstrated that both heart rate variability and cardiac baroreflex sensitivity were preserved in young unmedicated adults with MDD compared with healthy nondepressed young adults. Furthermore, in young adults with MDD, current depressive symptom severity was not associated with any indices of cardiac autonomic function.

Increasing Equity of Physical Activity Promotion for Optimal Cardiovascular Health in Adults: A Scientific Statement From the American Heart Association.

Fewer than 1 in 4 adults achieves the recommended amount of physical activity, with lower activity levels reported among some groups. Addressing low levels of physical activity among underresourced groups provides a modifiable target with the potential to improve equity in cardiovascular health. This article (1) examines physical activity levels across strata of cardiovascular disease risk factors, individual level characteristics, and environmental factors; (2) reviews strategies for increasing physical activity in groups who are underresourced or at risk for poor cardiovascular health; and (3) provides practical suggestions for physical activity promotion to increase equity of risk reduction and to improve cardiovascular health. Physical activity levels are lower among those with elevated cardiovascular disease risk factors, among certain groups (eg, older age, female, Black race, lower socioeconomic status), and in some environments (eg, rural). There are strategies for physical activity promotion that can specifically support underresourced groups such as engaging the target community in designing and implementing interventions, developing culturally appropriate study materials, identifying culturally tailored physical activity options and leaders, building social support, and developing materials for those with low literacy. Although addressing low physical activity levels will not address the underlying structural inequities that deserve attention, promoting physical activity among adults, especially those with both low physical activity levels and poor cardiovascular health, is a promising and underused strategy to reduce cardiovascular health inequalities.

Left ventricular mass index and risk of cognitive decline in a general elderly population: Tanushimaru cohort study

Background and Aims : Elevated cardiovascular disease risk factor burden is a recognized contributor to poorer cognitive function. Recent cohort study suggested that higher N-terminal pro-B-type natriuretic peptide levels predicted incident dementia. However, there is little study of the longitudinal association between left ventricular (LV) structure and future cognitive decline. Therfore, we hypothesied that LV structure is associated with cognitive decline.

Are we targeting the right population? Application of eligibility criteria of 10 dementia prevention trials to the general population

AbstractBackgroundVarious trials have investigated the effects of multidomain lifestyle interventions on cognitive decline, but with limited clinical benefit. This could be due to these trials targeting older individuals with elevated cardiovascular risk factors, who often already qualify for preventive intervention. We aimed to determine clinical implications of trials by application of trial eligibility criteria and prognosis to the general population.MethodWe conducted a literature review and sought to identify large (≥500 participants), phase‐3 multidomain lifestyle trials for the prevention of cognitive decline or dementia. We extracted eligibility criteria, and applied these to participants from the population‐based Rotterdam Study (40≥years). We determined what proportion of trial‐eligible individuals qualified for preventive intervention according to American (ACC/AHA) and European (ESC/EAS) cardiovascular prevention guidelines. To evaluate whether trial inclusion criteria optimally captured individuals at high risk of dementia that could benefit most, we compared remaining lifetime dementia risk, with 10‐year predicted risks for cardiovascular events.ResultOut of 1448 abstracts, we five identified published dementia prevention trials (DR’s EXTRA, FINGER, preDIVA, MAPT and HATICE). Through trial registries, we identified another five (US‐POINTER, MIND‐CHINA, MYB‐Trial, J‐Mint and AgeWell.de) that were ongoing at time of the search. Among 5381 Rotterdam Study participants (mean age 72 years, 58% women), eligibility across published trials ranged from 48% for MAPT to 87% for PREDIVA, largely mimicking estimates from original trial reports. Variability in eligibility was wider for ongoing trials, and ranged from 0.9% for US‐POINTER, to 21% for Age‐Well.de up to 94% for J‐Mint. The vast majority of individuals already qualified for both lifestyle and pharmaceutical interventions (e.g. statins or antihypertensives) based on their cardiovascular risk (ACC/AHA: from 65% for DRs EXTRA to 93% for AgeWell.de, for ESC/EAS: from 60% for DR’s EXTRA to 83% for HATICE). Remaining lifetime dementia risk was higher when individuals were at lower 10‐year cardiovascular risk.ConclusionMultidomain dementia prevention trials target a segment of the population that already qualifies for preventive interventions based on their cardiovascular risk according to cardiology guidelines. These findings call for adapted recruitment strategies in dementia trials, to adequately capture the population at risk in whom maximum benefit can be achieved.

Abstract 11505: Left Ventricular Mass Index and Risk of Cognitive Decline in a General Elderly Population (Tanushimaru Cohort Study)

Introduction: Elevated cardiovascular disease risk factor burden is a recognized contributor to poorer cognitive function. Recent cohort study suggested that higher N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels predicted incident dementia. However, there is little study of the longitudinal association between left ventricular (LV) structure and future cognitive decline. Hypothesis: LV structure is associated with cognitive decline. Methods: We recruited 1943 participants (mean age: 65.8±11.3 years, male 39.9%) as a population-based sample of Tanushimaru, Japan in 2009 and followed 837 adults in 2018 after excluding those with heart disease history. The subjects received 2-dimensional echocardiography to quantify LV mass index (LVMI) in 2009. The 30-point Mini-Mental State Examination (MMSE) was used to assess cognitive function in 2009 and in 2018. We classified MMSE scores ≦23, 24-27, ≥28 as dementia, mild cognitive impairment (MCI) and normal cognition (NC). Multivariable logistic regression analyses were performed to examine the association between LVMI and cognitive decline. Results: Mean MMSE scores in 2009 and in 2018 among 837 participants were 28.1±2.0 and 28.4±2.3, respectively. Cognitive status progressed from NC to MCI/dementia in 19.3% (96/498) or from NC/MCI to dementia in 2.9% (24/826). Mean LVMI levels were 81.9±19.7g/m2 in men and 76.5±18.4g/m2 in women. Conversion from NC to MCI/dementia was not associated with LVMI, while larger LVMI was significantly associated with the progression from NC/MCI to dementia (p=0.002). Age, sex-adjusted odds ratio for progression to dementia was 1.50 (95% confidence interval, 1.16-1.97) as LVMI increased by 10 g/m2. The association was independent of body mass index, systolic blood pressure, and microalbuminuria. LVMI > 90.6 g/m 2 in men and > 99.9 g/m 2 in women accurately predicted progression to dementia (p < 0.0001). These cutoff points were smaller in men and larger in women than the current criteria for LV hypertrophy. Conclusions: Larger LVMI was not associated with early stage of cognitive decline, but can be a risk factor for progression to dementia. We recommend to carefully evaluate cognitive function among at-risk individuals with larger LVMI.

Direct and indirect effects of obesity on progression of carotid arterial injury in youth.

Increased carotid intima-media thickness (cIMT) is associated with cardiovascular (CV) events in adults and with elevated CV risk factors in youth. The aim of this study was to determine whether obesity has an direct or indirect association with cIMT. Structural equation modeling was used to elucidate pathways for obesity to change cIMT. Complete data were collected twice on 294 participants (mean age 17.5 years, 16% with type 2 diabetes). Latent baseline and follow-up cIMT, BMI, and CV risk factors were analyzed with SAS 9.4. Model fit was assessed. There were increases in BMI, mean arterial pressure (MAP), low-density lipoprotein cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, C-reactive protein, and glucose and a decrease in insulin and glycosylated hemoglobin over 5 years (all p < 0.05). Only bulb (0.031 mm) and internal (0.027 mm) cIMT increased (all p < 0.001). Significant direct effects on cIMT change were baseline MAP (β 0.23), BMI z score (β 0.16), change in glucose (β 0.37), and age (β 0.37; all p < 0.05). Change in MAP showed a trend (β 0.14, p = 0.10). BMI also had a significant indirect effect (β 0.17), whereas non-HDL demonstrated no significant effect. Baseline adiposity drives increasing blood pressure and glucose in high-risk youth leading to accelerated accumulation of carotid arterial injury. Prevention of acquisition of obesity in youth is critical in slowing development of CV disease.

Elevated Cardiovascular Risk Factors at Time of Allotransplant Do Not Impact Survivals in Adult Patients: A Retrospective Study of 194 Cases

Background: Cardiovascular events are complications responsible for morbidity and mortality after allogeneic stem cell transplantation (allo-SCT). However, little is known regarding the impact on outcomes of cardiovascular risk factors at the time of allo-SCT in adult patients.Patients and Methods: The primary objective of this retrospective study was to examine the impact on overall (OS) and disease-free (DFS) survival of pre-transplant well-recognized cardiovascular risk factors in a large cohort of adult allo-SCT recipients. All adults (>18 years old) allotransplanted in our center between January 2011 and December 2014 (n=194) were eligible for the study. Of the numerous cardiovascular risk factors defined previoulsy (Mahmood SS et al, Lancet 2014), ten were considered here. A point of 1 was attributed to each of them if present, allowing to build various scores for statistical analysis.Results: The cohort comprised 120 males and 74 females with a median age of 56 years old (range: 21-70). The initial disease was of myeloid lineage for 58% and lymphoid for 42%. Most of the patients were in complete remission (CR) at transplant (CR1 n=78, CR2 or more n=38, Partial remission (PR) 1 n=4, PR2 or more n=30, active disease n=44). Ninety-one patients had received a myeloablative conditioning regimen while 79 and 24 had received a reduced-intensity or a sequential regimen, respectively. Donors were as follows: sibling n=68, haplo-identical n=4, matched unrelated donor n=76, mismatched (9/10) unrelated donor n=19, unrelated cord blood n=27. Peripheral blood stem cells was the main source of graft (n=151) while 16 cases received bone marrow. All patients had a left ventricular ejection fraction >50% at the time of transplantWith a median OS of 66 months (95% CI 34-66), 2-year OS and DFS were 59.3% +/- 3.6 and 51% +/- 3.6, respectively, for the whole group. Overall incidences of grade 2-4 acute and chronic GVHD were 55% and 31% while overall incidences of relapse and NRM were 36% and 16%, respectively.For each considered cardiovascular risk factor at transplant, the number of patients involved was as follows: male >50 years old (n=75)/female >60 years old (n=24), smoking activity (active or stopped within the last three years, n=86), overweight (BMI>/= 25) and obesity (BMI >/= 30) (n=85), hypertension (n=26), diabetes mellitus (n=7) and previous first-degree familial history of coronary disease (n=4). For factors characterizing dyslipidemia, these numbers were: total cholesterol >2 g/L n=95, total triglycerides >1.5 g/L n=98, HDL cholesterol <0.4g/L n= 67, and LDL-cholesterol >1.6g/L n=29).In univariate analysis, HDL cholesterol below or above 0.4 g/L and active disease at transplant were the only factors significantly associated with lower 2 year OS (50.6%+/-6.1 vs 65.6%+/-4.5 vs, p=0.02; and 38.3%+/-7.6 vs CR: 68.3%+/-4.4 vs PR: 61%+/-8.5, p=0.001, respectively) and DFS (55.6%+/-4.7 vs 41.5%+/-6, p=0.04; and 28.7%+/-7.1 vs CR 59.1%+/-4.6 vs PR 51%+/-7.1, p=0.0002, respectively). However, in multivariate analysis, only the disease status at the time of transplant retained significance (OS: HR 1.7. 95%CI 1.3-2.24, p=0.0001; and DFS: HR 1.7, 95%CI 1.3-2.17, p=0.0001).When considering various cardiovascular risk scores for statistical analysis, none were predictive of survivals in patients.After transplant, the incidence of cardiovascular events was 8.2% (n=16/194) within the first year and 12.5% (n=16/127) for patients alive after one year. None of the patients died of cardiovascular disease.Conclusion: Elevated cardiovascular risk factors at the time of allo-SCT do not impact survivals in adult patients. Therefore, their presence should not lead to reconsider the procedure and may not make the patients at higher risk for allo-SCT. DisclosuresTouzeau:AbbVie: Research Funding. Moreau:Millennium: Consultancy, Honoraria; Onyx Pharmaceutical: Consultancy, Honoraria; Takeda: Honoraria; Celgene, Janssen, Takeda, Novartis, Amgen, Roche: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Bristol-Myers Squibb: Honoraria; Amgen: Honoraria.

Childhood-onset depression and arterial stiffness in young adulthood

ObjectivesThe literature on childhood-onset depression and future compromised vascular function is suggestive but limited. The objective of this study was to determine if arterial stiffness, a predictor of future cardiovascular disease (CVD), measured in young adulthood, is associated with childhood-onset depression. MethodsCardiometabolic risk factors and pulse wave velocity (PWV), a measure of arterial stiffness, were cross-sectionally assessed in young adults with a history of childhood-onset depression (clinical diagnosis of major depressive episode or dysthymic disorder; N = 294 probands; initially recruited via child mental health facilities across Hungary; mean age of first depressive episode = 10.4 years), their never-depressed full biological siblings (N = 269), and never-depressed controls (N = 169). The mean ages of probands, siblings, and controls at the PWV visit were 25.6, 25.0, and 21.7 years, respectively, and 8.8% of the probands were in a current depressive episode. ResultsControlling for age, sex, age*sex, education, and family clusters, PWV (m/s) did not statistically differ across the groups (probands = 7.01; siblings = 6.98; controls = 6.81). However, after adjusting for key covariates, there were several across-group differences in CVD risk factors: compared to controls, probands and siblings had higher diastolic blood pressure and lower high-density lipoprotein cholesterol, probands had higher triglycerides, and siblings had higher body mass index (all p < 0.05). ConclusionWe found limited evidence of an association between a history of childhood-onset depression and young adulthood arterial stiffness. However, our findings of elevated cardiovascular risk factors in those with childhood-onset depression suggest that pediatric depression may predispose to increased CVD risk later in life and warrants further investigation.

Different Indicators of Adiposity and Fat Distribution and Cardiometabolic Risk Factors in Patients with Type 2 Diabetes.

This study aimed to evaluate the effect of adiposity and fat distribution on the odds of elevated cardiovascular risk factors among adults with type 2 diabetes mellitus. The present cross-sectional study included 2,427 adults with type 2 diabetes mellitus. Body fat was assessed by dual-energy x-ray absorptiometry. Multivariate-adjusted logistic regression was used to estimate effects of adiposity parameters on elevated hemoglobin A1c (HbA1c , ≥7.0%), hypertension (blood pressure ≥140/90 mmHg), and elevated low-density lipoprotein (LDL) cholesterol (≥2.6 mmol/L). The multivariable-adjusted odds ratio (OR) for elevated HbA1c was 0.82 (95% CI: 0.70-0.96) for each SD increase in leg fat mass. The multivariable-adjusted OR for hypertension was 1.15 (95% CI: 1.00-1.32) for each SD increase in android fat mass. Multivariable-adjusted ORs for elevated LDL cholesterol ranged from 1.16 (95% CI: 1.00-1.35) to 1.27 (95% CI: 1.06-1.51) for each SD increase in arm and android fat mass and percentage of total, truncal, arm, and android fat. Each SD increase in BMI, truncal-to-leg fat ratio, and android-to-gynoid fat ratio was significantly associated with increased risks of elevated HbA1c , hypertension, and elevated LDL cholesterol. Subcutaneous fat in the lower body was associated with a more favorable glycemic profile, but not blood pressure or lipid profile, whereas central adiposity was associated with poor control of cardiovascular risk factors among patients with type 2 diabetes mellitus.

Abstract 14786: Women Wait Longer Than Men for First EKG When Self-Presenting With Suspected Acute Coronary Syndrome, A Review of the Irish National ACS Registry

Introduction: Women suffer longer delay times until diagnosis and treatment when presenting with ACS, despite cardiovascular disease being the biggest cause of death amongst women. European guidelines recommend that women and men with suspected ACS are managed according to a common protocol. We aimed to investigate whether differential system delay existed for women versus men due to longer wait time for initial EKG testing in patients who self-presented to the emergency room with suspected ACS, bypassing the pre-hospital diagnosis and warning system Methods: We retrospectively reviewed the Irish national ACS registry and identified all cases of patients who self-presented to the emergency room between 2013-2018. Those patients for whom accurate time delays were not recorded were excluded. Baseline characteristics were compared for both groups. We determined the wait time from presentation to first EKG for both groups and performed a Mann-Whitney U test to test the difference between the groups. Results: Total number of self-presenters was 714 (women 154, men 560), representing 13.2% of all patients in the registry. We excluded 54 due to inaccurate time recordings; 14 were excluded due to first EKG performed by a family doctor in the community. Women were older than men (mean age 66.3 vs. 59.2yrs, P=0.0000012) and had similar rates of diabetes mellitus (10.4% vs. 11.9%, P=0.63). More women were current smokers (45.4% vs. 37.3%, P=0.11), more likely to be hypertensive (58.5% vs 44.5%, P=0.002) and have a diagnosis of hyperlipidaemia (56.7% vs. 46.8%, P=0.048). Median wait times were longer for women compared with men: 25.0 min (IQ 13-74) vs. 18.0 min (IQ 8-42)( P=0.002)(see Figure). Conclusion: Women self-referring with suspected ACS to the emergency room had longer wait times for their first EKG compared with men despite being more likely to have an elevated cardiovascular risk factor profile. Differential wait times for EKG is an important contributor to system delay.

Left Ventricular Mass Index Is Associated With Cognitive Function in Middle-Age: Bogalusa Heart Study.

Elevated cardiovascular disease risk factor burden is a recognized contributor to poorer cognitive function; however, the physiological mechanisms underlying this association are not well understood. We sought to assess the potential mediation effect of left ventricular (LV) remodeling on the association between lifetime systolic blood pressure and cognitive function in a community-based cohort of middle-aged adults. Nine hundred sixty participants of the Bogalusa Heart Study (59.2% women, 33.8% black, aged 48.4±5.1 years) received 2-dimensional echocardiography to quantify relative wall thickness, LV mass, and diastolic and systolic LV function; and a standardized neurocognitive battery to assess memory, executive functioning, and language processing. Multivariable linear regression assessed the association of cardiac structure and function with a global composite cognitive function score, adjusting for traditional cardiovascular disease risk factors. Mediation analysis assessed the effect of LV mass index on the association between lifetime systolic blood pressure burden and cognitive function. There were 233 (24.3%) and 136 (14.2%) individuals with concentric LV remodeling and concentric LV hypertrophy, respectively. Each g/m2.7 increment in LV mass index was associated with a 0.03 standardized unit decrement in global cognitive function (P=0.03). Individuals with concentric LV remodeling and isolated diastolic dysfunction had the poorest cognitive function, and a greater ratio between early mitral inflow velocity and early diastolic mitral annular velocity (E/e') was associated with poorer cognitive function, even after adjustment for LV mass index (B=-0.12; P=0.03). A total of 18.8% of the association between lifetime systolic blood pressure burden and midlife cognitive function was accounted for by LV mass index. Cardiac remodeling partially mediates the association between lifespan systolic blood pressure burden and adult cognition in individuals without dementia or clinical cardiovascular disease. Slowing or reversing the progression of cardiac remodeling in middle-age may be a novel therapeutic approach to prevent cognitive decline.

ADVANCING DIGITAL HEALTH INTERVENTIONS AS A CLINICALLY APPLIED SCIENCE FOR BLOOD PRESSURE REDUCTION: A SYSTEMATIC REVIEW AND META-ANALYSIS

The combination of pharmacotherapy with lifestyle counselling is recommended by international heart health organizations as the optimal strategy to reduce risk factors for cardiovascular disease (CVD). Trials of digital counselling demonstrate significant efficacy in lowering systolic blood pressure (SBP), but heterogeneity of SBP outcomes is a common problem. Our initial aim was to evaluate randomized controlled trials (RCT) of digital counselling for blood pressure reduction that were cited in guideline statements by international cardiovascular societies, or in major meta-analyses. This evaluation focused on efficacy and heterogeneity of SBP outcomes, and how these outcomes were associated with (i) the degree of complexity of the intervention protocol, and (ii) whether an explicit model of behaviour change or counselling was used. Our literature search focused on relevant taskforce guidelines, scientific statements, systematic reviews and meta-analyses published since 2010 and noted in EMBASE, Cochrane Library, psycINFO, and PubMed databases. We extracted RCT’s of digital counselling for blood pressure reduction in populations with elevated cardiovascular risk factors or cardiovascular disease. Sixteen trials met inclusion criteria: pooled n = 4,408, 30% female, 89% prescribed antihypertensive medications. SBP reduction was characterized by a low-moderate standardized mean difference (SMD) of 0.39 (95% CI: 0.3, 0.5) between Digital Intervention vs. Control groups, with high-moderate heterogeneity (Iˆ2 = 69%). This was equivalent to -8.2 mmHg for digital counselling (95% CI: -7.9 to -8.4) versus -4.2 mmHg for control (95% CI: -4.4 to -3.9), p < 0.0001. Figure 1 illustrates similar low-moderate treatment effects for SBP outcomes, with high-moderate heterogeneity, among trials with complex interventions of 3-5 treatment components. Therapeutic outcome was optimal for SBP reduction, with a moderate SMD and moderate heterogeneity (Iˆ2 = 49%) when the intervention had multiple therapeutic components and was organized by a theoretical framework of behaviour change or counselling. This translated to -4.8 mmHg for digital counselling (95% CI: -5.09 to -4.57) versus -1.4 mmHg (95% CI: -1.89 to -0.99) for Control. Digital health interventions optimize the efficacy of medical therapy for SBP reduction. Therapeutic outcomes are improved with adherence to recommended guidelines for the intervention design, including the use of a clinically organized protocol and multiple therapeutic components in the intervention. Given that digital health applications are projected to grow at an accelerated rate, there is opportunity to promote disruptive change in the design of behavioural counselling interventions for CVD risk factor reduction through the synergy of clinical science and digital technology.

Effects of thyroxine on adhesion molecules and proinflammatory cytokines secretion on human umbilical vein endothelial cells.

Thyroid dysfunction is associated with elevated cardiovascular risk factors and atherosclerosis. It could be suggested that, hyperthyroidism is related to a higher prevalence of arterial abnormalities. Therefore, evaluating the endothelial dysfunction (ED) related biomarkers seem to be an important issue. It is not clear whether endothelial cells are biologically responsive to thyroid hormones (THs) or how THs induces the production of endothelial cells (EC)-derived proinflammatory mediators. Hence, in this study the effects of thyroxine (T4) on ED and inflammatory related mediators were evaluated. Human umbilical vein endothelial cells was used as endothelial cell model which was treated with concentrations of 50, 100, 200 nmol/L of T4 in various exposure times. In the following, gene and protein expression levels of EC-related markers including intercellular adhesion molecule-1 (ICAM-1), vascular endothelial growth factor (VEGF), and E-selectin were determined using real time polymerase chain reaction (RT-PCR) and western blotting methods. Also, interleukin-6 (IL-6) and tumor necrosis factor (TNF-α) protein levels as proinflammatory cytokines were determined by enzyme linked immunosorbent assay (ELISA) method. Gene and protein expression analysis revealed that T4 treatments up regulated the levels of VEGF, ICAM-1, and E-selectin as ED markers. In addition, T4-treated cells had higher significant levels of IL-6 and TNF-α versus untreated cells in different incubation times. This study proposed the atherosclerotic effects of thyroid hormone. Based on our findings, T4 had strong effects on the gene and protein expression levels of pro-inflammatory, angiogenesis, and ED major mediators associated with atherosclerosis development.

Generalizing Intensive Blood Pressure Treatment to Adults With Diabetes Mellitus

BackgroundControversy over blood pressure (BP) treatment targets for individuals with diabetes is in part due to conflicting perspectives about generalizability of available trial data. ObjectiveThe authors sought to estimate how results from the largest clinical trial of intensive BP treatment among adults with diabetes would generalize to the U.S. population. MethodsThe authors used transportability methods to reweight individual patient data from the ACCORD (Action to Control Cardiovascular Risk in Diabetes) BP trial (N = 4,507) of intensive (goal systolic BP <120 mm Hg) versus standard (goal systolic BP <140 mm Hg) treatment to better represent the demographic and clinical risk factors of the U.S. population of adults with diabetes (data from NHANES [National Health and Nutrition Examination Survey] 2005 to 2014, n = 1,943). The primary outcome was the first occurrence of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. Analysis used weighted Cox proportional hazards regression models with robust standard errors. ResultsThe ACCORD BP sample had less racial/ethnic diversity and more elevated cardiovascular risk factors than the NHANES participants. Weighted results significantly favored intensive BP treatment, unlike unweighted results (hazard ratio for primary outcome in intensive versus standard treatment in weighted analyses: 0.67, 95% confidence interval: 0.49 to 0.91; in unweighted analyses: hazard ratio: 0.88, 95% confidence interval: 0.73 to 1.07). Over 5 years, the weighted results estimate a number needed to treat of 34, and number needed to harm of 55. ConclusionsAfter reweighting to better reflect the U.S. adult population with diabetes, intensive BP therapy was associated with significantly lower risk for cardiovascular events. However, data were limited among racial/ethnic minorities and those with lower cardiovascular risk.

Impact of Glycemic Levels in Type 2 Diabetes on Periodontitis.

Aim:The aim is to study the effect of glycemic level in Type 2 diabetes and cardiovascular risk factors on periodontal health.Materials and Method:Type 2 diabetic and nondiabetic patients in the age group of 35–80 years (n = 1700) were recruited for the study. Periodontal examination included as follows: Probing depth, clinical attachment level (CAL), gingival recession, and bleeding on probing. Periodontitis was diagnosed based on the CAL levels and diabetes was diagnosed based on glycated hemoglobin (HbA1c) levels. Body mass index, total cholesterol, triglyceride, and low-density lipoprotein (LDL) were assessed for cardiovascular risk. Patients were characterized into two groups as follows: diabetic (n = 1235) and nondiabetic (n = 465). Sociodemographic variables included were: age, sex, obesity, smoking, duration of diabetes, and periodontitis were assessed. SPSS version 20.0.1.0 was used for all the statistical assessments.Conclusion:HbA1c and lipid levels were statistically significant with the severity of periodontitis (odds ratio [OR] [95% confidence interval [CI]: HbA1c 1.34 [1.019–1.21]; Total cholesterol 1.01 [1.03–1.42]; triglycerides 1.01 [1.01–1.14]; LDL 1.028 [1.08–1.71]). Smoking and obesity were also found to be significantly associated with the presence of periodontitis [OR (95% CI): smoking 1.35 (1.10–1.67); obesity 1.23 (1.73–2.05)]. The study concluded that uncontrolled HbA1c levels and elevated cardiovascular risk factors significantly increase the severity of periodontitis in Type 2 diabetes mellitus.

Socially disadvantaged city districts show a higher incidence of acute ST-elevation myocardial infarctions with elevated cardiovascular risk factors and worse prognosis

BackgroundThe importance of socioeconomic status (SES) for coronary heart disease (CHD)-morbidity is subject of ongoing scientific investigations. This study was to explore the association between SES in different city-districts of Bremen/Germany and incidence, severity, treatment modalities and prognosis for patients with ST-elevation myocardial infarctions (STEMI).MethodsSince 2006 all STEMI-patients from the metropolitan area of Bremen are documented in the Bremen STEMI-registry. Utilizing postal codes of their home address they were assigned to four groups in accordance to the Bremen social deprivation-index (G1: high, G2: intermediate high, G3: intermediate low, G4: low socioeconomic status).ResultsThree thousand four hundred sixty-two consecutive patients with STEMI admitted between 2006 and 2015 entered analysis. City areas with low SES showed higher adjusted STEMI-incidence-rates (IR-ratio 1.56, G4 vs. G1). This elevation could be observed in both sexes (women IRR 1.63, men IRR 1.54) and was most prominent in inhabitants <50 yrs. of age (women IRR 2.18, men IRR 2.17). Smoking (OR 1.7, 95%CI 1.3–2.4) and obesity (1.6, 95%CI 1.1–2.2) was more prevalent in pts. from low SES city-areas. While treatment-modalities did not differ, low SES was associated with more extensive STEMIs (creatine kinase > 3000 U/l, OR 1.95, 95% CI 1.4–2.8) and severe impairment of LV-function post-STEMI (OR 2.0, 95% CI 1.2–3.4). Long term follow-up revealed that lower SES was associated with higher major adverse cardiac or cerebrovascular event (MACCE)-rates after 5 years: G1 30.8%, G2 35.7%, G3 36.0%, G4 41.1%, p (for trend) = 0.02. This worse prognosis could especially be shown for young STEMI-patients (<50 yrs. of age) 5-yr. mortality-rates(G4 vs. G1) 18.4 vs. 3.1%, p = 0.03 and 5-year-MACCE-rates (G4 vs. G1) 32 vs. 6.3%, p = 0.02.ConclusionsThis registry-data confirms the negative association of low socioeconomic status and STEMI-incidence, with higher rates of smoking and obesity, more extensive infarctions and worse prognosis for the socio-economically deprived.

Elevated cardiovascular risk factors in multiple sclerosis

BackgroundMultiple sclerosis (MS) is associated with elevated cardiovascular mortality. To prevent this a better understanding of their CVD risk factors and interrelations is necessary. MethodsMS patients (n = 52) and healthy controls (HC, n = 24) were matched for age, height, weight, body mass index and physical activity. Body composition, resting blood pressure (BP), resting heart rate (HR), glucose tolerance, HbA1c, blood lipids (HDL, LDL, total cholesterol, triglyceride concentrations) and c-reactive protein concentrations were analyzed. Regression analyses identified independent CVD risk factors and their interrelations in MS. ResultsIn MS and compared to HC, fat mass (25.1 ± 1.2kg vs. 17.9 ± 1kg), fat percentage (33.8 ± 1.2% vs. 28.4 ± 1.5%), systolic (130 ± 1.8mmHg vs. 120 ± 2.9mmHg) and diastolic (79 ± 1.1mmHg vs. 71 ± 1.9mmHg) BP, resting HR (72 ± 1.4bpm vs. 60 ± 2bpm), blood triglycerides (113.8 ± 8.6mg/dl vs. 98.2 ± 17.4mg/dl), fasting (13.5 ± 2.9mU/l vs. 7.2 ± 0.8mU/l) and 2h insulin (71.9 ± 12.5mU/l vs. 35.8 ± 8.1mU/l), 2h glucose (6.3 ± 0.5mmol/l vs. 4.8 ± 0.5mmol/l) and HOMA index (3.7 ± 1.1 vs. 1.7 ± 0.2) were significantly (p < 0.05) elevated. Total cholesterol, blood HDL and LDL concentrations did nog differ between groups (p < 0.05). Regression analyses indicated that MS is independently associated with elevated fat mass/percentage, systolic and diastolic BP and HR and in MS fat mass appears to be an independent contributor of the other measured CVD risk factors in MS. ConclusionPersons with MS have an increased risk for CVD and fat mass appears to be an important risk factor. Therefore, normalizing whole body fat should be an essential part of MS treatment.