Future Cardiovascular Risk Research Articles

Abstract P331: Higher Allostatic Load Score is Associated With Early Cardiovascular Risk in Young South Africans. The AfricanPREDICT Study

Background: The Allostatic load score (ALS) is a composite score that measures the cumulative physiological burden of sustained exposure to stress and biological dysregulation. ALS has markers capture risk in 4 domains (neuro-endocrine, metabolic, cardiovascular, and immunological). Higher ALS in adults predict cardiovascular disease (CVD), but it is unknown whether ALS is associated with CVD risk in youth and young adults (YA), and whether the risk and association would differ at such an early age. Aims: In youth and YA we compared 1) the total ALS; 2) the cardiovascular profile according to high and low ALS; and 3) the association of ALS with markers of CVD. Methods: Participants in the African PRospective study on the Early Detection and Identification of Cardiovascular disease and HyperTension (AfricanPREDICT) were 587 youth<24years (48% Male, 21±2 years) and 579 YA≥24years (49% Male, 27±2 years) were evaluated. The ALS was calculated from fasting biomarkers using the upper quartile population distribution of dehydroepiandrosterone (DHEA), cortisol, interleukin-6 (IL-6), C-reactive protein (hsCRP), BMI, systolic-BP, diastolic-BP, and lower quartile of HDL-cholesterol. The upper quartile of ALS in the whole population was defined as high ALS. Retinal vessel analyses, pulse wave velocity, and echocardiography were obtained and associations with ALS determined by regression analyses adjusted for sex, ethnicity, cotinine, gamma-glutamyl-transferase (GGT) and physical activity. Results: ALS median range was 1-8, and a high ALS of >3 was observed in 35% of youth, and 47% YA. In youth with high ALS, ALS associated with narrower retinal arteries (Adj R 2 :0.16, β-coefficient, -1.73, (95%CI), -2.95, -0.94), P =0.052), greater pulse wave velocity (Adj R 2 :0.56, 0.75 (0.48, 1.98), P =0.021), increased left ventricular mass index (Adj R 2 :0.61, 2.21 (0.43, 8.46) P =0.048), lower left ventricular function (global longitudinal strain) (Adj R 2 :0.37, -0.45 (-1.06, -0.06) P =0.015). Similarly, in YA with high ALS, ALS associated with narrower retinal arteries (Adj R 2 :0.43, -4.54 (-6.58, -2.50), P <0.001), greater pulse wave velocity (Adj R 2 :0.44, 0.62 (0.09, 1.17), P =0.043), increased left ventricular mass index (Adj R 2 :0.53, 2.62 (1.52, 5.76) P =0.032), lower diastolic function (E/A ratio) (Adj R 2 :0.27, -0.11 (-0.18, -0.04) P =0.002). Conclusion: Youth and YA with high ALS had a more adverse CVD risk profile and greater association with markers of cardiovascular aging compared to their low ALS counterparts. ALS and allostatic dysregulation should be evaluated in youth and YA, when assessing current and future cardiovascular risk.

Abstract 14: Infant Gut Microbiome is Associated With Child Blood Pressure at Age 3 and 6 Years: Findings From a Danish Birth Cohort

Background: Experimental germ-free mice studies indicate that the gut microbiome affects blood pressure (BP). To our knowledge, no epidemiologic studies have investigated whether childhood BP, which portends future cardiovascular disease risk, is influenced by the infant gut microbiome—a microbiome that is less confounded by lifestyle. Understanding the link between gut microbiome and BP will shed light on gut microbiome as a modifiable way to improve child cardiovascular health. Objectives: To examine prospective associations of the gut microbiome at 1 month and 1 year with systolic BP (SBP) at 3 and 6 years, and to examine if the associations differed by breastfeeding duration over infancy. Methods: We used data from children followed up from birth to six years of age in the Copenhagen Prospective Studies on Asthma in Childhood 2010 cohort in Denmark. We measured infant gut microbiome at 1mo and 1y by 16S rRNA sequencing (V4 region). Research staff measured child BP in triplicate using standardized protocols during scheduled study visits at 3y and 6y. We analyzed microbiome features at each time point during infancy in relation to SBP at 3y and 6y, separately. We focused on Shannon index as a measure of microbiome alpha diversity, and differential abundance of microbial taxa. We assessed effect measure modification by breastfeeding duration at time of microbiome measurement. We adjusted models for maternal diet score during pregnancy, preeclampsia, gestational age, birth weight, and breastfeeding duration (when it was not a modifier). Results: Of 526 children included in the analysis, 49% were female and 78% were born vaginally. A 1-unit increment in Shannon index at 1mo was associated with -0.35 mmHg (-1.61, 0.91) lower SBP at 3y and -1.21 (-2.20, -0.23) lower SBP at 6y. Lower abundance of Bacteroides and higher abundance of Staphylococcus at 1mo was associated with higher SBP at 3y only (both FDR-P <0.05); no microbial taxa at 1mo were significantly associated with SBP at 6y. As for microbiome at 1y, associations differed by breastfeeding duration ( P-interaction < 0.10). In children who were breastfed beyond 1y, a 1-unit increment in Shannon index at 1y was associated with -2.94 mmHg (-5.59, -0.28) and -1.02 mmHg (-3.24, 1.19) lower SBP at 3y (n=56) and 6y (n=72), respectively. In contrast, in children who were breastfed shorter than 1y, 1-unit increment in Shannon index was associated with 0.55 (-0.75, 1.85) and 1.26 (0.28, 2.24) higher SBP at 3y (n=298) and 6y (n=382), respectively. After multivariable adjustment, no microbial taxa at 1y were significantly associated with SBP at 3y or 6y. Conclusions: Higher gut microbiome Shannon diversity and higher Bacteroides and lower Staphylococcus at 1 month was prospectively associated with higher child BP at 3 and 6 years of age. Microbiome Shannon diversity at 1 year was also associated with child BP, however, associations depended on breastfeeding.

Abstract 57: Distinct Gestational Blood Pressure Trajectories Predict Pregnancy, Birth, and Postpartum Health in a Low-Income Hispanic Population

Objective: Blood pressure (BP) typically drops to a nadir around 20 to 24 gestation weeks in a normal pregnancy. Distinct BP trajectories over pregnancy could reveal underlying cardiovascular function and predict future cardiovascular risk, but little is known about BP trajectories in Hispanic women. We aim to identify BP trajectories during pregnancy among low-income, Hispanic women. Methods: In the prospective Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) pregnancy cohort, we abstracted clinic BP measures of 732 participants who had an average of 12 BP measures over pregnancy, ranging from 4 to 41 weeks. We used latent class mixture modeling to identify BP trajectories. We examined associations of population characteristics, pregnancy and birth outcomes, and 1-year postpartum BP with the identified trajectories. Results: We identified three distinct BP trajectories ( Figure ). Compared to the majority (class 1, n=569), the consistently high class 2 (14.8%, 108) was characterized by a higher pre-pregnancy BMI (ppBMI, 32.3±7.6 vs. 27.6 ±6.1 Kg/m 2 ) and a higher proportion of having college or above education (21.3% vs. 14.9%), while the high-low-high U-shape class 3 (7.5%, 55) had a higher ppBMI (32.0±7.9 Kg/m 2 ) but lower proportion of having college or above education (9.1%). Risk of preeclampsia was the highest in class 3 (43.6%), followed by class 2 (10.2%) and class 1 (6.0%), while the risk of gestational diabetes was the highest in class 2 (14.8%), followed by class 1 (7.9%) and class 3 (7.3%). Birthweight and gestational duration were both significantly lower in class 3 than classes 1 and 2. One-year postpartum systolic BP was significantly higher in class 2 (120.2±16.0 mmHg) and class 3 (122.4±16.0 mmHg) than class 1 (111.7±26.2 mmHg) after adjusting for maternal age, pre-pregnancy BMI, parity, and education. Conclusion: Elevated blood pressure may develop into district trajectories in pregnancy that further predict pregnancy and birth outcomes, as well as postpartum blood pressure.

Abstract P244: Gestational Glucose Intolerance is Associated With Hypertensive Disorders of Pregnancy in a Large Hospital-Based Multiethnic Cohort

Introduction: Hypertensive disorders of pregnancy (HDP) are associated with higher future cardiovascular risk. Treatment of gestational diabetes (GDM) has been shown to reduce the risk of HDP. It is unknown if women with gestational glucose intolerance (GGI), defined as abnormal GDM screening but without a GDM diagnosis, are at higher risk of HDP. Currently, GGI is not treated. Hypothesis: We tested the hypothesis that GGI pregnancies have increased odds of HDP. Methods: This is a retrospective cohort study of 41,706 singleton pregnancies delivered at an academic center. Based on the results of GDM screening and diagnostic tests, pregnancies were categorized as normal glucose tolerance (NGT, glucose loading test < 140 mg/dl), GGI (glucose loading test ≥140 mg/dl with 0 or 1 abnormal value on oral glucose tolerance testing [OGTT] thus without GDM), or GDM (≥ 2 abnormal values on OGTT). GGI was further classified into groups with zero (GGI-0) or 1 (GGI-1) abnormal OGTT values. We used laboratory, blood pressure, and delivery reports to capture HDP and exclude chronic hypertension. Generalized estimating equations for logistic regression were used to measure the risk of HDP after adjustment for age, 1st trimester BMI, parity, insurance, race/ethnicity, and marital status. A similar approach was used to test for associations between GGI and pre-eclampsia (PE). Results: A total of 84.5% of pregnancies were classified as NGT, 8.9% as GGI-0, 3.0% as GGI-1 and 3.6% as GDM. The unadjusted frequencies of HDP and PE were higher in GGI-1 (140 [11.2%] and 64 [5.1%] of 1,251) and GDM (165 [11.1%] and 94 [6.3%] of 1,485) compared to NGT (2,275 [6.5%] and 1,100 [3.1%] of 35,238) and GGI-0 (283 [7.6%] and 136 [3.6%] of 3,732). We observed greater odds of HDP in all 3 groups compared to NGT in adjusted models, and similar trends for PE (Figure 1). Conclusions: The risks of HDP and PE in GGI-1 are greater than for NGT pregnancies and similar to the risks in GDM. Our results suggest that women with GGI-1 should be considered for intervention, similar to GDM.

Abstract P509: Does HDL-C Classification as a Criterion for Metabolic Syndrome Contribute to Alleviated Risks of Future Atherosclerosis and Incident Diabetes Among Midlife Women? The Study of Women’s Health Across the Nation (SWAN)

Introduction: In women, metabolic syndrome (MetS) is identified when at least 3 of the following risk factors exist: waist circumference > 88 cm, HDL-C < 50 mg/dL, triglycerides (TG) ≥ 150 mg/dL, fasting glucose ≥ 110 mg/dL, and hypertension. However, previous studies challenged the belief that HDL-C is protective for midlife women, casting doubts on HDL-C as one of the criteria for diagnosing MetS in this population. Hypothesis: We hypothesize that among midlife women classified as having MetS based on criteria independent of HDL-C, HDL-C classification does not contribute to risk of future subclinical atherosclerosis or incident diabetes. Methods: Participants from the SWAN study with complete data on MetS were classified into the following groups: 1) no MetS or 2) MetS independent of HDL-C; which was classified into MetS with HDL-C ≥ 50 mg/dL (MetS high), or MetS with HDL-C < 50 mg/dL (MetS low). Carotid intima-media thickness (cIMT) was measured after 13.8±0.6 years of follow-up. Incident diabetes was recorded based on medication use, fasting glucose ≥ 126 mg/dL and/or self-reports over time. Linear regression and discrete-time survival analysis were used for analysis. Results: Among 2994 women age 45.9±2.7 years, 2528 had no MetS (88%), 85 had MetS high (3%), and 235 had MetS low (8%) at baseline. In model 1, compared to no MetS group, MetS high or low group had higher cIMT and higher odds of diabetes. The risk did not differ between MetS low vs. high group. Adjusting for levels of MetS criteria other than HDL-C explained the associations of each of the two MetS groups with cIMT. Conversely, MetS with low HDL-C remained associated with a higher risk of incident diabetes ( Table 1 ). Conclusions: Midlife women with MetS have elevated risk for incident diabetes and subclinical atherosclerosis regardless of HDL-C levels. The elevated risk is explained by levels of criteria of MetS other than HDL-C for cIMT but not for diabetes. Low HDL-C on top of other MetS criteria doesn’t contribute equally to future cardiovascular risk prediction in midlife women.

Women's Reproductive Milestones and Cardiovascular Disease Risk: A Review of Reports and Opportunities From the CARDIA Study.

In 1985 to 1986, the CARDIA (Coronary Artery Risk Development in Young Adults) study enrolled 5115 Black or White participants, including 2788 women, aged 18 to 30 years. Over the following 35 years, the CARDIA study amassed extensive longitudinal data on women's reproductive milestones, spanning menarche to menopause. Although not initially conceived as a study of women's health, >75 CARDIA study publications address relationships between reproductive factors and events with cardiovascular and metabolic risk factors, subclinical and clinical cardiovascular disease, and social determinants of health. The CARDIA study was one of the earliest population-based reports to note Black-White differences in age at menarche and associations with cardiovascular risk factors. Adverse pregnancy outcomes, particularly gestational diabetes and preterm birth, have been assessed along with postpartum behaviors, such as lactation. Existing studies have examined risk factors for adverse pregnancy outcomes and lactation, as well as their relationship to future cardiovascular and metabolic risk factors, diagnoses, and subclinical atherosclerosis. Ancillary studies examining components of polycystic ovary syndrome and ovarian biomarkers, such as anti-Müllerian hormone, have facilitated examination of reproductive health in a population-based cohort of young adult women. As the cohort transitioned through menopause, examination of the importance of premenopausal cardiovascular risk factors along with menopause has improved our understanding of shared mechanisms. The cohort is now aged in the 50s to mid-60s, and women will begin to experience a greater number of cardiovascular events as well as other conditions, such as cognitive impairment. Thus, in the next decade, the CARDIA study will provide a unique resource for understanding how the women's reproductive life course epidemiology informs cardiovascular risk, as well as reproductive and chronological aging.

Is a unified blood pressure threshold feasible in the current scenario?: Commentary on the article"130/80mmHg as a unifying hypertension threshold for office brachial, office central and ambulatory daytime brachial blood pressure": Commentary on the article"130/80mmHg as a unifying hypertension threshold for office brachial, office central and ambulatory daytime brachial blood pressure".

Is a unified blood pressure threshold feasible in the current scenario?: Commentary on the article"130/80mmHg as a unifying hypertension threshold for office brachial, office central and ambulatory daytime brachial blood pressure": Commentary on the article"130/80mmHg as a unifying hypertension threshold for office brachial, office central and ambulatory daytime brachial blood pressure".

The effect of adverse pregnancy outcomes on vascular aging in young women: the Kailuan study.

Adverse pregnancy outcomes (APOs) are at increased future cardiovascular risk and require effective risk mitigation. However, data regarding appropriate postpartum screening for young women with APOs are lacking. We aimed to investigate the association between APOs and vascular aging by the determination of high pulse wave velocity (PWV) in young women. Women who gave birth from 1990 to 2020 and underwent brachial-ankle pulse wave velocity (baPWV) assessments in the postpartum period were recruited. We excluded women with age ≥50 years at the baPWV assessment or missing postpartum health examinations. The history of APOs including hypertensive disorders of pregnancy, gestational diabetes, preterm delivery, and low birth weight were assessed by medical records. High PWV was defined as baPWV above the 90th percentile for different age group. Multivariable Logistic regression was used to evaluate the association of APOs and high PWV. 3193 participants were included in the analysis, including 912 (28.6%) individuals with APOs. The prevalence of high PWV in the non-APO group and the APOs group were 7.19% (164) and 13.9% (127), respectively (P < 0.05). Compared with non-APO group, the OR (95% CI) of APOs group was 1.67 (1.29-2.16). The risks in the 20-29, 30-39, and 40-49 age groups were 2.51 (1.13-5.59), 1.83 (1.30-2.59), and 1.35 (0.82-2.21) (P for trend <0.05). We conclude that APOs are risk factors of vascular aging for young women and the risk decreased with increasing age. BaPWV should be an important indicator for preventive cardiovascular risk management in young women with APOs. Clinical trial registration: Registration number ChiCTR-TNRC-11001489, http://www.chictr.org.cn/showproj.aspx?proj=8050 .

Use of clinical scores in young Australian adults for prediction of atherosclerosis in middle age

We sought to apply a simple cardiovascular health tool not requiring laboratory tests (the Fuster-BEWAT score, FBS) to predict subclinical atherosclerosis. This study included 2657 young adults (< 40 years of age). In the prognostic group (n = 894, followed for 13 years until aged 40–50 years at follow-up), the primary outcome was presence of carotid plaque measured by carotid ultrasound at follow-up. Of these 894 participants, 86 (9.6%) had unilateral, and 23 participants (2.6%) had bilateral, carotid plaques at follow-up. The baseline FBS was predictive of carotid plaque at follow-up [odds ratio OR = 0.86 (95% CI 0.77–0.96) per 1-SD increase in FBS], similar to prediction from Pooled Cohort Equation [PCE, OR = 0.72 (0.61–0.85) per 1-SD decrease in PCE]. Risk scores at baseline predicted outcomes more strongly than those at follow-up, and did so independently of any changes over 13 years of follow-up. Similar discrimination for predicting carotid plaque after 13 years was found for both baseline FBS [C-statistic = 0.68 (95% CI 0.62–0.74)] and PCE [C-statistic = 0.69 (95% CI 0.63–0.75)]. Application of this FBS prognostic information to a contemporary cohort of 1763 young adults anticipates the future development of plaque in 305 (17.3%), especially in the 1494 participants (85%) with ≤ 2 metrics of ideal health. In conclusions, FBS measured in young adulthood predicted atherosclerosis 13 years later in middle age, independent of score changes over the follow-up period, emphasizing the importance of early damage to vascular health. FBS may be a simple and feasible risk score for engaging low-risk young people with reduction of future cardiovascular risk.

Acute, but not chronic, aerobic exercise alters the impact of ex vivo LDL and fatty acid stimulation on monocytes and macrophages from healthy, young adults.

Elevated low-density lipoprotein (LDL) and triglyceride concentrations are associated with future cardiovascular risk in young adults. Conversely, chronic physical activity is generally accepted to reduce CVD risk. Atherosclerosis is a major underlying cause of CVD, and atherogenesis is mediated by peripheral monocytes and monocyte-derived macrophages. The study aimed to determine if an individual's physical activity level impacts the phenotype of monocytes and monocyte-derived macrophages when stimulated with LDL and fatty acid ex vivo. Peripheral blood mononuclear cells (PBMCs) were obtained from healthy, young adults of differing physical activity levels before and after a single bout of moderate intensity exercise (25min at 60% of VO2peak). PBMCs were stimulated with LDL and palmitate ex vivo prior to differentiation into macrophages. Monocyte subset percentages and monocyte-derived macrophage expression of phenotypic (CD86, CD206) and functional (CCR2, ERK 1/2) markers were evaluated by flow cytometry. Compared to baseline, ex vivo LDL and palmitate stimulation decreased (p = 0.038) non-classical monocyte percentage from 24.7 ± 3.2 to 21.5 ± 2.6% in all participants. When ex vivo lipid stimulation was preceded by acute exercise, non-classical monocyte percentage was similar to baseline levels (p = 0.670, 25.8 ± 2.15%). Macrophage CD86/CD206 was increased from 1.30 ± 0.14 to 1.68 ± 0.19 when preceded by acute exercise in all participants. No differences were observed between participants of differing physical activity levels. Findings suggest that acute exercise modulates monocyte phenotype after LDL and palmitate stimulation in a protective manner, however, chronic physical activity does not alter monocyte/macrophage responses to any experimental condition in this population.

Alliance for Innovation on Maternal Health: Consensus Bundle on Cardiac Conditions in Obstetric Care.

Cardiac conditions are the leading cause of pregnancy-related deaths and disproportionately affect non-Hispanic Black people. Multidisciplinary maternal mortality review committees have found that most people who died from cardiac conditions during pregnancy or postpartum were not diagnosed with a cardiovascular disease before death and that more than 80% of all pregnancy-related deaths, regardless of cause, were preventable. In addition, other obstetric complications, such as preeclampsia and gestational diabetes, are associated with future cardiovascular disease risk. Those with cardiac risk factors and those with congenital and acquired heart disease require specialized care during pregnancy and postpartum to minimize risk of preventable morbidity and mortality. This bundle provides guidance for health care teams to develop coordinated, multidisciplinary care for pregnant and postpartum people with cardiac conditions and to respond to cardio-obstetric emergencies. This bundle is one of several core patient safety bundles developed by the Alliance for Innovation on Maternal Health that provide condition- or event-specific clinical practices for implementation in appropriate care settings. The Cardiac Conditions in Obstetric Care bundle is organized into five domains: 1) Readiness , 2) Recognition and Prevention , 3) Response , 4) Reporting and Systems Learning , and 5) Respectful Care . This bundle is the first by the Alliance to be developed with the fifth domain of Respectful Care . The Respectful Care domain provides essential best practices to support respectful, equitable, and supportive care to all patients. Further health equity considerations are integrated into elements in each domain.

Postpartum perception of cardiovascular risk and risk modification in patients with hypertensive disorders of pregnancy

Hypertensive disorders of pregnancy (HDP) are associated with future cardiovascular risk. We sought to assess risk-perception for future hypertension (HTN) among individuals with HDP undergoing postpartum blood pressure monitoring and a lifestyle intervention. We utilized data from a randomized clinical trial of overweight and obese individuals with HDP and no pre-pregnancy HTN. Participants were randomized postpartum to usual care, home blood pressure monitoring (HBPM), and HBPM with a remote lifestyle intervention. We collected data at enrollment and one year postpartum to assess effects of the interventions, disease severity, and need for anti-hypertensive medications on participants’ perception of risk. Questions were adapted from Kim and Walker’s validated survey of chronic diabetes risk in those with gestational diabetes (scale 1-5; 5 indicating higher risk perception). We compared data across groups using Wilcoxon rank-sum test. Multivariable logistic regression was used to model odds of ‘high’ risk perception at follow-up (score >4). Complete data was available on 129 of the 148 participants (87%). Overall, those with HDP saw themselves as high risk for developing HTN (median 4 [IQR 3,4]) at enrollment (mean 10.5±6.1 weeks postpartum). Participants randomized to lifestyle intervention or HBPM had higher risk perception at one-year postpartum compared to control (median change 0 [0,1] and 0 [0,1] vs 0 [-1, 0], respectively, p=0.04). After controlling for arm, those with preterm deliveries or who were on anti-hypertensives were more likely to see themselves as high risk compared to those with term deliveries or who did not need medications, respectively. Risk perception for future HTN in individuals with HDP is high overall. It is affected by factors such as disease severity and anti-hypertensive use and may be higher following participation in postpartum interventions. Understanding factors that influence risk perception following HDP may lead to more informed counseling and the adoption of programs which modify risk perception and mitigate future CVD risk.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

First body fat reference curves for Macedonian children and adolescents: the MAKFIT study.

Introduction: childhood obesity is a worldwide chief health problem. Along with body mass index, body fat percentile values can also be used to predict future cardiovascular and metabolic health risks. Objective: the study's aim is to define the percentile values and curves about the fat tissue percentage through which the childhood and adolescent overweight/obesity in the Republic of North Macedonia will be diagnosed. Methods: the research was conducted on a sample of 15,075 children and adolescents aged six to 14 years (7,627 boys and 7,448 girls). Body fat percentage was established by bioelectrical impedance. The LMS method was used in percentile values and curves' construction. Results: the boys' 50th percentile curve shows that the body fat percentage average value has a slight growth from seven to ten years of age, but after their 10th it begins to drop continuously until the age of 14 years. At the same time, the girls' body fat percentage average value increases continuously from six to 14 years of age. Conclusion: since body mass index cannot always establish body fat content, the direct assessment of body fat by bioelectrical impedance would be of great advantage for pediatric and clinical decisions. Therefore, the study provides referent percentile norms for the body fat percentage of healthy Macedonian children and adolescents. For this purpose, a practical and clinically applicable method was used. The obtained referent percentile norms can be useful in assessing overweight and obesity in Macedonian children and adolescents.

PS-BPP02-2: BLOOD PRESSURE VARIABILITY PREDICTS THE DEVELOPMENT OF HYPERTENSION IN NORMOTENSIVE INDIVIDUALS

Objective: Hypertension is one of the important risk factors for atherosclerosis leading to cardiovascular diseases. Although several factors have been reported as predictors of new onset of hypertension, the association of blood pressure (BP) variability in normotensive subjects with future development of hypertension is not intensively discussed. We tested the hypothesis that the yearly variability of BP in normotensive subjects predicts new onset of hypertension. Design and Methods: Subjects who participated in our annual physical check-up program for 5 years in a row during 2008 and 2013 were screened (screening period) and those under antihypertensive medication or with the average BP for the 5 visits ≧ 140/90 mmHg were excluded. The rest of 2006 participants (male = 1287) were eligible in the present study. Standard deviation (SD) and coefficient of variation (CV) of their systolic BP (SBP) during the 5 consecutive visits were calculated (screening period) and, then, they were followed up for the next 5 years (follow-up period). The onset of hypertension was defined as average BP during the follow-up period ≧ 140/90 mmHg or the use of antihypertensive medications. Results: The average, SD, and CV of SBP were 118.7 ± 10.0 mmHg, 7.44 ± 2.98 mmHg, and 6.30 ± 2.54%, respectively. During the follow-up, hypertension developed in 259 subjects, with the incidence being more frequent in male (n = 180, 14.0%) than female subjects (n = 79, 11.0%). In retrospective analysis, the average (128.7 ± 7.7 vs. 117.2 ± 9.5 mmHg, p &lt; 0.001) and SD (8.05 ± 3.48 vs. 7.34 ± 2.89 mmHg, p &lt; 0.001) were higher in subjects with than without future hypertension, whereas CV was not different in the both groups (6.28 ± 2.73 vs. 6.30 ± 2.51%). Non-adjusted odds ratio (OR) (95% confidence interval [CI]) of average, SD and CV for the incident hypertension were 1.169 (1.146–1.193), 1.078 (1.034–1.124) and 0.997 (0.947–1.050), respectively. Multivariate logistic regression analysis adjusted for age, gender, family history of hypertension, frequent alcohol consumption (six or seven times per week), current smoking, body mass index, heart rate, serum creatinine, fasting plasma glucose, LDL-cholesterol, and triglyceride at baseline demonstrated that average (OR [95%CI] = 1.193 [1.138–1.187]) and SD (1.058 [1.014–1.105]), but not CV (0.992 [0.941–1.046]), were associated with new onset hypertension. Similar results were obtained using diastolic BP (data not shown). Conclusions: In normotensive subjects, an increase in year-to-year variability as well as average of SBP may be a predictor of the new onset of hypertension. Careful interpretation of year-to-year BP variability is necessary for evaluation of future cardiovascular risk in normotensive individuals.

STUDY OF LIPID PROFILE AND ATHEROGENIC INDEX IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE

Objectives: The present study’s design investigated the lipid parameters level and atherogenic index in atherosclerosis and cardiovascular disease risk development in chronic obstructive pulmonary disease patients. Methods: The study consists of 108 clinically diagnosed and confirmed spirometry-stable chronic obstructive pulmonary disease (COPD) patients (Mild, Moderate, and Severe), and the controls were 36 healthy individuals of the same age and sex. Blood samples were collected and the lipid profile was done. The atherogenic index of all COPD patients was calculated using the values of lipid parameters. Results: The observation revealed that as compared to the control group, total cholesterol, triglycerides, low-density lipoproteins (LDL), and very LDLs were significantly (p&lt;0.001) raised in all the COPD sub-groups, and high-density lipoproteins levels showed significantly (p&lt;0.001) decreasing levels in all COPD groups as compared to controls. The COPD sub-group has a higher atherogenic risk (p&lt;0.001) than controls. Conclusion: In COPD patients with dyslipidemia, there is an increased atherogenic risk, which predicts future cardiovascular risk.

Pre-eclampsia and cardiovascular risk: a long-term nationwide cohort study on over 120 000 Finnish women

ObjectivesTo investigate the impact of pre-eclampsia on the future cardiovascular risk in Finnish womenDesignA registry-based nationwide controlled cohort study.SettingWomen hospitalised for pre-eclampsia in 1969–1993 and control women with a history...

Resting heart rate variability as a diagnostic marker of cardiovascular dysautonomia in postural tachycardia syndrome.

Postural orthostatic tachycardia syndrome (POTS) is a disorder of the autonomic nervous system characterised by orthostatic intolerance and orthostatic tachycardia without hypotension. Heart rate variability (HRV) is the most reliable and objective tool for assessing autonomic dysfunction severity. In the present study, we aimed to investigate HRV changes in resting supine position, predicting severity and cardiovascular risk in patients with POTS. We compared 100 POTS patients with 160 healthy controls matched for age and gender in a case-control design. Along with clinical characterization, heart rate variability was evaluated using ambulatory 5min ECG in lead II and expressed in frequency and time-domain measures. The resting heart rate of patients with POTS was significantly higher than that of healthy controls. In HRV measures, root mean square successive difference of RR intervals (RMSSD), total and high frequency (HF) powers were statistically lower with an increased low frequency (LF) to high-frequency ratio in patients with POTS compared to healthy controls. Further, stepwise logistic regression analysis showed increased basal HR and LF/HF as significant predictors of POTS and its severity. This is the first study on a large cohort of patients with POTS from India wherein HRV was assessed. The study showed reduced parasympathetic activity andincreased sympathetic activity in patients with POTS compared to healthy controls. These findings of increased resting heart rate and LF/HF were found to be potential predictors of POTS and future cardiovascular risks, which need to be replicated in a larger and more homogenized cohort.

Highlighting the trajectory from intrauterine growth restriction to future obesity.

During the last decades several lines of evidence reported the association of an adverse intrauterine environment, leading to intrauterine restriction, with future disease, such as obesity and metabolic syndrome, both leading to increased cardiovascular and cancer risk. The underlying explanation for this association has firstly been expressed by the Barker's hypothesis, the "thrifty phenotype hypothesis". According to this hypothesis, a fetus facing an adverse intrauterine environment adapts to this environment through a reprogramming of its endocrine-metabolic status, during the crucial window of developmental plasticity to save energy for survival, providing less energy and nutrients to the organs that are not essential for survival. This theory evolved to the concept of the developmental origin of health and disease (DOHaD). Thus, in the setting of an adverse, f. ex. protein restricted intrauterine environment, while the energy is mainly directed to the brain, the peripheral organs, f.ex. the muscles and the liver undergo an adaptation that is expressed through insulin resistance. The adaptation at the hepatic level predisposes to future dyslipidemia, the modifications at the vascular level to endothelial damage and future hypertension and, overall, through the insulin resistance to the development of metabolic syndrome. All these adaptations are suggested to take place through epigenetic modifications of the expression of genes without change of their amino-acid sequence. The epigenetic modifications leading to future obesity and cardiovascular risk are thought to induce appetite dysregulation, promoting food intake and adipogenesis, facilitating obesity development. The epigenetic modifications may even persist into the next generation even though the subsequent generation has not been exposed to an adverse intrauterine environment, a notion defined as the "transgenerational transfer of environmental information". As a consequence, if the increased public health burden and costs of non-communicable chronic diseases such as obesity, hypertension, metabolic syndrome and type 2 diabetes have to be minimized, special attention should be laid to the healthy lifestyle habits of women of reproductive age, including healthy diet and physical activity to be established long before any pregnancy takes place in order to provide the best conditions for both somatic and mental health of future generations.

Levothyroxine Therapy and Predictors of Cardiovascular Risk in Clinical Hypothyroidism: A Prospective Cohort Study

Background Hypothyroidism is associated with hypoadiponectinemia, insulin resistance, and increased cardiovascular risk. The association of adiponectin, insulin resistance, and future cardiovascular risk in clinical hypothyroidism and the effect of levothyroxine are non-conclusive because of the contradictory results. The present prospective cohort study has been conducted to evaluate the effect of levothyroxine on serum adiponectin, insulin resistance, and cardiovascular risk in patients with clinical hypothyroidism. Methods Sixty patients with clinical hypothyroidism who were prescribed levothyroxine were recruited following selection criteria and changes in Zulewski's score, glycemic parameters, homeostatic model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), lipid profile, serum adiponectin, serum high-sensitivity C-reactive protein(hs-CRP), cardiovascular risk indices, and Framingham risk score were assessed 12 weeks post-levothyroxine therapy. Receiver operating characteristic (ROC) analysis was done to detect the cut-off for adiponectin levels to differentiate between responders and non-responders. Neural network models were created to predict the risk of cardiovascular morbidity. Results Post-levothyroxine therapy, there was a significant improvement in body mass index(BMI) (p = 0.025), diastolic blood pressure (p = 0.021), Zulewski's score (p< 0.001), serum insulin (p = 0.005), fasting sugar (p < 0.001), serum adiponectin (p < 0.001), thyroid profile (p < 0.001), total cholesterol (p < 0.001), low-density lipoprotein (p < 0.001), high-density lipoprotein (p = 0.007), triglycerides (p = 0.002), and subcutaneous fat (p = 0.015). Serum adiponectin showed significant improvement in hypothyroid patients compared to euthyroid individuals (mean difference: -2.21; 95% CI: -2.52 to -1.91; p < 0.001). Mean difference in insulin resistance (HOMA-IR: 0.3, p < 0.001; QUICKI: -0.002, p < 0.001) and cardiovascular risk (atherogenic index: 0.12, p = 0.04; coronary risk index: 0.14, p = 0.038; Framingham risk score: 0.65, p = 0.041) also showed improvement. Serum adiponectin and thyroid-stimulating hormone levels were directly correlated with insulin resistance and cardiovascular risk scores. Conclusion The reduced serum adiponectin level and increased cardiovascular risk in clinical hypothyroidism were improved with hormone replacement, and serum adiponectin level was found to be a good prognostic marker for the treatment response.

Undetected hypertension in primary care – a public health iceberg?

Abstract Background Hypertension is largely asymptomatic and contributes to considerable lifetime cardiovascular morbidity and mortality, costing the NHS £2.1 billion annually. The national prevalence of hypertension is 13.7 % and lack of a national screening programme, despite meeting aspects of the Wilson Junger criteria, adds to delays in detection and treatment. Earlier detection could mitigate future cardiovascular risk. We wanted to understand the potential of detection of prehypertension in primary care to see if this fits the Wilson and Junger criteria for a screening programme. Methods GP records of adult patients n = 2178 with a known diagnosis of hypertension on the hypertension register from a practice population of 10,000 patients (prevalence is 22%.) were analysed for the prevalence of prehypertension systolic 120-139 mm hg and diastolic bp of 80-89. The average length of prehypertension, the time delay in detection and treatment were assessed, alongside the prevalence of clinical and therapeutic inertia. Results A retrospective analysis of a sample size of 1809 patients out of 2178 patients (83.1%) with known hypertension across 3 primary care sites over 20 years was undertaken. Of these 1809 patients, we found that 1095 patients (60.5%) were prehypertensive prior to being diagnosed. The mean time interval between detection of prehypertension to a formal hypertension diagnosis was 10.6 years, with a standard deviation of 7.89 years with no variation with age or sex. However, 588 patients (32.5%) did not have readings within the prehypertensive ranges prior to diagnosis and were opportunistically detected. 51 patients (2.82%) never had readings recorded within the prehypertensive range. Conclusions Prehypertension predates hypertension by an average of 10.6 years. Offering annual screening nationally to patients of risk groups e.g., those with a family history, obesity, and alcohol excess, would enable earlier detection, treatment, and considerable cost saving. Key messages • Prehypertension predates hypertension; therefore, hypertension meets the Wilson Junger criteria for earlier detection by a screening programme, which is lacking in the UK. • Offering a national scheme to screen for hypertension to those at a higher risk, can only be considered a benefit to the public and should be implemented.