Subclinical Cardiovascular Outcomes Research Articles

Subclinical thyroid dysfunction and the risk of incident atrial fibrillation: A systematic review and meta-analysis.

Thyroid hormones act on the cardiovascular system directly by modulating its function and indirectly by transcriptional regulation of gene expression in the heart and the vasculature. Studies have shown associations between overt and subclinical thyroid disorders and cardiovascular outcomes. The aim of this study was to perform a systematic review and meta-analysis to assess the potential relationships between subclinical hyper- and hypothyroidism and risk of atrial fibrillation (AF), and post-operative AF. MEDLINE and Scopus databases were searched from inception to 18th February 2023 for randomised controlled trials, case-control studies, and cohort studies which assessed the relationship between subclinical thyroid dysfunction and incident AF events. Risk of bias and the quality of evidence were assessed using the RoBANS tool and GRADE approach, respectively. Meta-analysis was conducted in Review Manager 5.4 using the Mantel-Haenszel statistical method and a random-effects model. Data are presented as risk ratios with 95% confidence intervals. Statistical heterogeneity amongst studies was assessed by the chi-squared (χ2) test and I2 statistic. p≤0.05 were considered significant. A total of 6467 records were identified, of which 10 cohort studies met the inclusion criteria. Both subclinical hyperthyroidism and subclinical hypothyroidism were associated with an increased risk of incident AF (risk ratio (RR), 1.99; 95% confidence interval (CI), 1.43-2.77; n = 5 studies; p<0.0001 and RR, 1.19; CI, 1.03-1.39; n = 7 studies; p = 0.02, respectively). Subgroup analysis for post-operative AF revealed marked heterogeneity between studies (I2 = 84%) and association with subclinical hypothyroidism was not significant (RR, 1.41; CI, 0.89-2.22; n = 3 studies; p = 0.15). The current evidence suggests that both subclinical hyperthyroidism and subclinical hypothyroidism are associated with increased risk of incident AF. Further investigation is required to determine potential causal links that would guide future clinical practice.

Prevalence of Pediatric Masked Hypertension and Risk of Subclinical Cardiovascular Outcomes: A Systematic Review and Meta-Analysis.

Masked hypertension (MH) occurs when office blood pressure is normal, but hypertension is confirmed using out-of-office blood pressure measures. Hypertension is a risk factor for subclinical cardiovascular outcomes, including left ventricular hypertrophy, increased left ventricular mass index, carotid intima media thickness, and pulse wave velocity. However, the risk factors for ambulatory blood pressure monitoring defined MH and its association with subclinical cardiovascular outcomes are unclear. A systematic literature search on 9 databases included English publications from 1974 to 2023. Pediatric MH prevalence was stratified by disease comorbidities and compared with the general pediatric population. We also compared the prevalence of left ventricular hypertrophy, and mean differences in left ventricular mass index, carotid intima media thickness, and pulse wave velocity between MH versus normotensive pediatric patients. Of 2199 screened studies, 136 studies (n=28 612; ages 4-25 years) were included. The prevalence of MH in the general pediatric population was 10.4% (95% CI, 8.00-12.80). Compared with the general pediatric population, the risk ratio (RR) of MH was significantly greater in children with coarctation of the aorta (RR, 1.91), solid-organ or stem-cell transplant (RR, 2.34), chronic kidney disease (RR, 2.44), and sickle cell disease (RR, 1.33). MH patients had increased risk of subclinical cardiovascular outcomes compared with normotensive patients, including higher left ventricular mass index (mean difference, 3.86 g/m2.7 [95% CI, 2.51-5.22]), left ventricular hypertrophy (odds ratio, 2.44 [95% CI, 1.50-3.96]), and higher pulse wave velocity (mean difference, 0.30 m/s [95% CI, 0.14-0.45]). The prevalence of MH is significantly elevated among children with various comorbidities. Children with MH have evidence of subclinical cardiovascular outcomes, which increases their risk of long-term cardiovascular disease.

Subclinical cardiovascular outcomes of acute exposure to fine particulate matter and its constituents: A glutathione S-transferase polymorphism-based longitudinal study

To explore the acute subclinical cardiovascular effects of fine particulate matter (PM2.5) and its constituents, a longitudinal study with 61 healthy young volunteers was conducted in Xinxiang, China. Linear mixed-effect models were used to analyze the association of PM2.5 and its constituents with cardiovascular outcomes, respectively, including blood pressure (BP), heart rate (HR), serum levels of high-sensitivity C-reactive protein (hs-CRP), 8-hydroxy-2′-deoxyguanosine (8-OHdG), tissue-type plasminogen activator (t-PA), and platelet-monocyte aggregation (PMA). Additionally, the modifying effects of glutathione S-transferase mu 1 (GSTM1) and glutathione S-transferase theta 1 (GSTT1) polymorphisms were examined. A 10 μg/m3 increase in PM2.5 was associated with −1.04 (95 % CI: −1.86 to −0.22) mmHg and −0.90 (95 % CI: −1.69 to −0.11) mmHg decreases in diastolic BP (DBP) and mean arterial BP (MABP) along with 1.83 % (95 % CI: 0.59–3.08 %), 5.93 % (95 % CI: 0.70–11.16 %) increases in 8-OHdG and hs-CRP, respectively. Ni content was positively associated with the 8-OHdG levels whereas several other metals presented negative association with 8-OHdG and HR. Intriguingly, GSTT1+/GSTTM1+ subjects showed higher susceptibility to PM2.5-induced alterations of DBP and PMA, and GSTT1-/GSTM1+ subjects showed higher alteration on t-PA. Taken together, our findings indicated that short-term PM2.5 exposure induced oxidative stress, systemic inflammation, autonomic alterations, and fibrinolysis in healthy young subjects. Among multiple examined metal components Ni appeared to positively associated with systematic oxidative stress. In addition, GST-sufficient subjects might be more prone to PM2.5-induced autonomic alterations.

Greetings From the Editor of Clinical Thyroidology

Clinical ThyroidologyVol. 34, No. 6 Greetings from the EditorFree AccessGreetings From the Editor of Clinical ThyroidologyAngela M. LeungAngela M. LeungSearch for more papers by this authorPublished Online:13 Jun 2022https://doi.org/10.1089/ct.2022;34.235-236AboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail DEAR COLLEAGUESWelcome to the June issue of Clinical Thyroidology. This issue begins with a review by Dr. Kenneth Burman, who summarizes a study on suboptimal thyroid hormone replacement. Drs. Ricardo Correa and Ricardo Villela discuss a study done in patients with subclinical hyperthyroidism and cardiovascular outcomes, while Drs. Eijun Nishihara and Takashi Akamizu review the findings of a recent trial of rituximab use in young patients with Graves’ disease.On the topic of thyroid nodules and thyroid cancer, Dr. Benjamin Gigliotti comments on a survey study summarizing respondents’ viewpoints of the various risk-stratification systems available for estimating malignancy risk. Drs. N. Rhea Udyavar and Lilah Morris-Wiseman review a study reporting the associations between thyroid autoimmunity and incident thyroid cancer, while Dr. Ulla Feldt-Rasmussen describes a Danish study assessing the relationships between education, socioecononomic status, and thyroid cancer incidence.The potential need for levothyroxine replacement in patients who undergo hemithyroidectomy for low-risk papillary thyroid cancer is always an interesting clinical question. Drs. Erivelto Volpi and Leonardo Volpi summarize a retrospective trial that studied this question. This issue also features a review by Drs. Anupam Kotwal and Whitney Goldner, who examine a recent study reporting the characteristics of patients with BRAF V600E–mutant papillary thyroid cancer. Drs. Sara Duffus and Lindsay Bischoff discuss a study assessing the differences between Hürthle-cell and follicular thyroid carcinomas. Finally, Dr. Mayumi Endo summarizes the findings of a phase 3 trial studying treatment with selumetinib and radioactive iodine in patients with high-risk differentiated thyroid cancer.Clinical Thyroidology will continue to feature select highlighted abstracts presented at the American Thyroid Association's 2021 annual meeting. In this issue, Drs. Tiba Abdulwahid and Karen Selk share their case report entitled “A Rare Hideaway.” I invite all our readers to learn about the interesting clinical course they describe.As always, we invite our readers to join us through our social media channels. Through these other ways of communication, we discuss content featured in each month's issue and other issues related to hot topics in the clinical thyroid literature:Twitter:https://twitter.com/clinicalthyroid(@clinicalthyroid)Facebook:https://www.facebook.com/ThyroidAssociationLinkedIn:https://www.linkedin.com/company/american-thyroid-associationYoutube:https://www.youtube.com/user/thyroidorgAlso note that most of the material covered in Clinical Thyroidology is also translated into shorter lay summaries in our sister journal, Clinical Thyroidology for the Public [CTFP] (https://www.thyroid.org/patient-thyroid-information/ct-for-patients), that is edited by Dr. Alan Farwell and his team each month. The summaries in CTFP may be of use to patients and the public who are interested in reading more about recently published studies in the clinical thyroid literature.I hope that each issue provides helpful reviews, commentaries, editorials, and perspectives regarding how best to treat patients with thyroid disease. Guidelines for submitting Letters to the Editor and select Guest Editorials that cover timely and innovative aspects of clinical thyroid disease management may be found at https://home.liebertpub.com/publications/clinical-thyroidologyand174/623/for-authors.Thank you again for your interest in Clinical Thyroidology. Please feel free to send me any questions or comments at clinicalthyroidology@thyroid.org.Warmest regards,Angela M. Leung, MD, MScEditor-in-Chief, Clinical ThyroidologyFiguresReferencesRelatedDetails Volume 34Issue 6Jun 2022 Information© Copyright 2022, Mary Ann Liebert, Inc.To cite this article:Angela M. Leung.Greetings From the Editor of Clinical Thyroidology.Clinical Thyroidology.Jun 2022.235-236.http://doi.org/10.1089/ct.2022;34.235-236Published in Volume: 34 Issue 6: June 13, 2022PDF download

Fine particulate matter air pollution and subclinical cardiovascular outcomes: A longitudinal study in 15 Chinese cities

AimsAlthough previous studies have linked short-term exposure to fine particulate matter (PM2.5) air pollution with various molecular biomarkers of cardiovascular system, limited evidence is available for indicators at clinical or subclinical levels. We examined the associations between short-term PM2.5 exposure and a range of clinical or subclinical indicators of cardiovascular health in general population. Methods and resultsA longitudinal repeated-measure study was conducted among 247,640 participants who repeatedly visited health examination centers in 15 typical cities across China from 2013 to 2020. A total of 19 well-established indicators of cardiovascular risk or injury were evaluated and air quality data at nearest fixed-site monitors were collected. Linear mixed-effects models with distributed lag models were used to analyze the potentially lagged effects of PM2.5. The average daily PM2.5 concentration was 48 μg/m3 during the study period. PM2.5 exposure was associated with significant changes of 16 indicators with the effects generally peaked on lag 0 to 3 day. For an interquartile range (IQR) elevation (37 μg/m3) in PM2.5 concentrations over lag 0–7 day, the cumulative percentage changes were 0.50% to 1.27% in heart rates and blood pressure, 0.10% to 5.04% in inflammatory markers, −0.29% to 1.39% in blood viscosity parameters, −0.67% to 3.45% in blood lipids, 0.89% in blood homocysteine, 0.13% to 0.78% in myocardial enzymes, and 3.03% in pulse wave velocity. These associations were not substantially changed after adjusting concomitant exposures to gaseous pollutants. ConclusionShort-term exposure to PM2.5 may induce early cardiovascular effects in general population, including acute inflammation, myocardial injury, increased blood viscosity, vascular stiffness and hyperlipidemia.

Two-year change in weight status and high carotid intima-media thickness in Chinese children.

No studies have assessed the association between change in weight status and subclinical cardiovascular outcomes in children. To examine the association of change in weight status over 2 years with carotid intima-media thickness (cIMT) among Chinese children. A total of 1184 children aged 6-11 years at baseline with complete data were included, and there were 1073 children after excluding those with cIMT ≥ sex- and age-specific 90th percentile values at baseline. Overweight (including obesity) at baseline or follow-up was defined by criteria for overweight and obesity for Chinese school-aged children and adolescents. High cIMT at follow-up was defined as cIMT ≥ age- and sex-specific 90th percentile based on the study population at follow-up. Compared with children who were in persistent normal-weight group, those in the incident or persistent overweight groups had higher cIMT change (incident overweight: β=0.0149, p < 0.05; persistent overweight: β =0.0068, p < 0.05) and had higher odds of high cIMT at follow-up (incident overweight: odds ratio [OR]=3.58, 95% confidence interval [CI]=1.34-9.61; persistent overweight: OR=13.41, 95% CI=7.58-23.73). In contrast, there was no significant increase in cIMT change (β=0.0106, p > 0.05) and odds of high cIMT (OR=2.50, 95% CI=0.69-9.01) in the resolution group. Children who developed overweight or maintained overweight over 2 years had increased odds of high cIMT, whereas those able to resolve their overweight status had a similar odds of developing high cIMT in childhood at follow-up. These findings highlight the potential role of managing weight status among children to preserve vascular health.

Blood pressure and long-term subclinical cardiovascular outcomes in low-risk young adults: Insights from Hanzhong adolescent hypertension cohort.

Stage 1 hypertension, newly defined by the 2017 American College of Cardiology (ACC)/American Heart Association (AHA) hypertension guideline, has been the subject of significant interest globally. This study aims to assess the impact of the new blood pressure (BP) stratum on subsequent subclinical cardiovascular outcomes in low‐risk young adults. This longitudinal study consisted of 1020 young adults (47.7% female; ages 18–23 years) free of cardiovascular disease from the Hanzhong Adolescent Hypertension Cohort with up to 25‐year follow‐up since 1992–1995. Outcomes were available through June 2017. Young adults with stage 1 hypertension accounted for 23.7% of the cohort. When it comes to middle adulthood, subjects with early life stage 1 hypertension were more likely to experience BP progression, and they had a 1.61‐fold increased risk of high‐risk brachial‐ankle pulse wave velocity (baPWV) and a 2.92‐fold risk of left ventricular hypertrophy (LVH) comparing with their normotensive counterparts. Among participants without any active treatment in midlife, the risk associated with stage 1 hypertension for BP progression was 2.25 (95% confidence interval [CI] = 1.41–3.59), high‐risk baPWV was 1.58 (95% CI = 1.09–2.79), LVH was 2.75 (95% CI = 1.16–6.48), and subclinical renal damage (SRD) was 1.69 (95% CI = 1.02–2.82) compared with the normal BP group. Overall, young adults with stage 1 hypertension had significantly higher risks for midlife subclinical cardiovascular outcomes than normotensive subjects. BP management targeting low‐risk young adults is of importance from both clinical and public health perspectives.

Early Cardiovascular Risk in E-cigarette Users: the Potential Role of Metals

Electronic cigarettes (e-cigs) are a source of metals. Epidemiologic and experimental evidence support that metals are toxic to the cardiovascular system. Little is known, however, about the role that e-cig metals may play as toxicants for the possible cardiovascular effects of e-cig use. The goal of this narrative review is to summarize the evidence on e-cig use and metal exposure and on e-cig use and cardiovascular toxicity and discuss the research needs. In vitro studies show cytotoxicity and increased oxidative stress in myocardial cells and vascular endothelial cells exposed to e-liquids and e-cig aerosols, with effects partially reversed with antioxidant treatment. There is some evidence that the heating coil plays a role in cell toxicity. Mice exposed to e-cigs for several weeks showed higher levels of oxidative stress, inflammation, platelet activation, and thrombogenesis. Cross-over clinical experiments show e-cig use alters nitric oxide-mediated flow-mediated dilation, endothelial progenitor cells, and arterial stiffness. Cross-sectional evidence from large nationally representative samples in the USA support that e-cig use is associated with self-reported myocardial infarction. Smaller studies found associations of e-cig use with higher oxidized low-density protein and heart variability compared to healthy controls. Numerous studies have measured elevated levels of toxic metals in e-cig aerosols including lead, nickel, chromium, and manganese. Arsenic has been measured in some e-liquids. Several of these metals are well known to be cardiotoxic. Numerous studies show that e-cigs are a source of cardiotoxic metals. Experimental studies (in vitro, in vivo, and clinical studies) show acute toxicity of e-cigs to the vascular system. Studies of long-term toxicity in animals and humans are missing. Longitudinal studies with repeated measures of metal exposure and subclinical cardiovascular outcomes (e.g., coronary artery calcification) could contribute to determine the long-term cardiovascular effects of e-cigs and the potential role of metals in those effects.

Acute cardiovascular health effects in a panel study of personal exposure to traffic-related air pollutants and noise in Toronto, Canada

Urban populations are often simultaneously exposed to air pollution and environmental noise, which are independently associated with cardiovascular disease. Few studies have examined acute physiologic responses to both air and noise pollution using personal exposure measures. We conducted a repeated measures panel study of air pollution and noise in 46 non-smoking adults in Toronto, Canada. Data were analyzed using linear mixed-effects models and weighted cumulative exposure modeling of recent exposure. We examined acute changes in cardiovascular health effects of personal (ultrafine particles, black carbon) and regional (PM2.5, NO2, O3, Ox) measurements of air pollution and the role of personal noise exposure as a confounder of these associations. We observed adverse changes in subclinical cardiovascular outcomes in response to both air pollution and noise, including changes in endothelial function and heart rate variability (HRV). Our findings show that personal noise exposures can confound associations for air pollutants, particularly with HRV, and that impacts of air pollution and noise on HRV occur soon after exposure. Thus, both noise and air pollution have a measurable impact on cardiovascular physiology. Noise should be considered alongside air pollution in future studies to elucidate the combined impacts of these exposures in urban environments.

The kidney, subclinical thyroid disease and cardiovascular outcomes in older patients.

ObjectiveThyroid hormones have been implicated to play a role in cardiovascular disease, along with studies linking thyroid hormone to kidney function. The aim of this study is to investigate whether kidney function modifies the association of subclinical thyroid dysfunction and the risk of cardiovascular outcomes.MethodsIn total, 5804 patients were included in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). For the current analysis, 426 were excluded because of overt thyroid disease at baseline or 6 months, 266 because of inconsistent thyroid function at baseline and 6 months, 294 because of medication use that could influence thyroid function, and 16 because of missing kidney or thyroid values. Participants with normal fT4 were classified, based on TSH both at inclusion and 6 months, into three groups: subclinical hypothyroidism (TSH >4.5 mIU/L); euthyroidism (TSH = 0.45–4.5 mIU/L); and subclinical hyperthyroidism (TSH <0.45 mIU/L). Strata of kidney function were made based on estimated glomerular filtration rate into three clinically relevant groups: <45, 45–60, and >60 mL/min/1.73 m2. The primary endpoint consists of death from coronary heart disease, non-fatal myocardial infarction and (non)fatal stroke.ResultsMean age was 75.3 years, and 49.0% patients were male. Mean follow-up was 3.2 years. Of all participants, 109 subjects (2.2%) had subclinical hypothyroidism, 4573 (94.0%) had euthyroidism, and 182 (3.7%) subclinical hyperthyroidism. For patients with subclinical hypothyroidism, euthyroidism, and subclinical hyperthyroidism, primary outcome occurred in 9 (8.3%), 712 (15.6%), and 23 (12.6%) patients, respectively. No statistically significant relationship was found between subclinical thyroid dysfunction and primary endpoint with adjusted hazard ratios of 0.51 (0.24–1.07) comparing subclinical hyperthyroidism and 0.90 (0.58–1.39) comparing subclinical hypothyroidism with euthyroidism. Neither was this relationship present in any of the strata of kidney function, nor did kidney function interact with subclinical thyroid dysfunction in the association with primary endpoint (P interaction = 0.602 for subclinical hyperthyroidism and 0.388 for subclinical hypothyroidism).ConclusionsIn this secondary analysis from PROSPER, we found no evidence that the potential association between thyroid hormones and cardiovascular disease is modified by kidney function in older patients with subclinical thyroid dysfunction.

"The relationship between cumulative unfair treatment and intima media thickness and adventitial diameter: The moderating role of race in the study of women's health across the nation": Correction to Peterson et al. (2016).

The Study of Women's Health Across the Nation is a longitudinal study of midlife women. Cumulative unfair treatment was calculated as the average of unfair treatment assessed over 10 years at 6 time points. Subclinical cardiovascular disease, specifically carotid intima media thickness and adventitial diameter, was assessed via carotid ultrasound conducted at study year 12 in 1,056 women. We tested whether cumulative unfair treatment was related to subclinical cardiovascular disease via linear regression, controlling for demographic factors including socioeconomic status and cardiovascular risk factors. The relation between unfair treatment and subclinical cardiovascular disease significantly varied by race (ps < .05), with unfair treatment related to higher intima media thickness (B = .03, SE = .01, p = .009) and adventitial diameter (B = .02, SE = .009, p = .013) only among Caucasian women. No significant relations between unfair treatment and subclinical cardiovascular disease outcomes were observed for African-American, Hispanic, and Chinese women. Our findings indicate that cumulative unfair treatment is related to worse subclinical cardiovascular disease among Caucasian women. These findings add to the growing literature showing that Caucasian women's experience of unfair treatment may have detrimental health implications. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Longitudinal evaluation of a household energy package on blood pressure, central hemodynamics, and arterial stiffness in China

BackgroundCardiovascular diseases are the leading contributors to disease burden in China and globally, and household air pollution exposure is associated with risk of cardiovascular disease. ObjectivesWe evaluated whether subclinical cardiovascular outcomes in adult Chinese women would improve after distribution of an energy package comprised of a semi-gasifier cookstove, water heater, chimney, and supply of processed biomass fuel. MethodsWe enrolled 204 households (n = 205 women) from 12 villages into a controlled before- and after-intervention study on cardiovascular health and air pollution in Sichuan Province. The intervention was distributed to 124 households during a government-sponsored rural energy demonstration program. The remaining 80 households received the package 18 months later at the end of the study, forming a comparison group. One woman from each household had their blood pressure (BP), central hemodynamics, and arterial stiffness measured along with exposures to air pollution and demographic and household characteristics, on up to five visits. We used a difference-in-differences mixed-effects regression approach with Bayesian inference to assess the impact of the energy package on sub-clinical cardiovascular outcomes. ResultsWomen who did not receive the energy package had greater mean decreases in brachial systolic (−4.1 mmHg, 95% credible interval (95%CIe) −7.3, −0.9) and diastolic BP (−2.0 mmHg, 95%CIe −3.6, −0.5) compared with women who received the package (systolic: −2.7, 95%CIe −5.0, −0.4; diastolic: −0.3, 95%CIe −1.4, 0.8) resulting in slightly positive but not statistically significant difference-in-differences effect estimates of 1.3 mmHg (95%CIe −2.5, 5.2) and 1.7 mmHg (95%CIe −0.3, 3.6), respectively. Similar trends were found for central BP, central pulse pressure, and arterial stiffness. Air pollution exposures decreased on average for both treatment groups, with a greater range of reductions among women who did not receive the package (with package: −30% to −50%; without package: +2% to −69%), likely as a result of increased use of gas fuel and electric stoves among this group. Outdoor air quality changed very little over time. ConclusionsGasifier stoves have been widely promoted as the next generation of ‘clean-cooking’ technologies, however their effectiveness in improving health in real-world settings should be carefully evaluated and communicated before scaling up their implementation.

The route of administration, timing, duration and dose of postmenopausal hormone therapy and cardiovascular outcomes in women: a systematic review.

The effect of postmenopausal hormone therapy (HT) on cardiovascular disease (CVD) risk remains controversial. We aimed to systematically review the evidence regarding the role of dose, route of hormone administration, timing of initiation and duration of HT on cardiovascular risk among postmenopausal women. The electronic databases Medline Ovid, Web of Science and Cochrane Central were systematically searched to identify studies published before 30 January 2018. Reference lists, using Elsevier's Scopus, of the included studies were searched for further identification of relevant studies. Clinical trials and observational studies that assessed clinical and subclinical cardiovascular outcomes in relation to dose, route of administration, duration of use, or timing of HT initiation among postmenopausal women were included. Data were extracted by independent reviewers using a pre-designed data collection form. The Cochrane Collaboration's tool and the Newcastle-Ottawa Scale were used by two independent investigators to assess the risk of bias in RCTs and in prospective observational studies, respectively. In total, 33 unique studies (6 trials and 27 prospective observational studies) were identified, including a total of 2 588 327 women. The synthesis of the existing knowledge on this topic was challenging due to inconsistent findings between some studies, caused by substantial diversity in scientific rigor and quality across the available literature. Overall, the evidence did not support the concerns that oral or transdermal HT increases heart disease risk. Contrary, observational data showed that a beneficial cardioprotective effect can be observed even with use of low doses of oral HT (effect of 0.3 mg/day of oral conjugated equine estrogen was similar to that seen with the standard dose of 0.625 mg/day), but clinical trials to support a cardioprotective benefit of HT in primary prevention have not been identified. Furthermore, the current data suggested that oral and transdermal HT, in dose-dependent manner and irrespective of HT formulation, may increase thromboembolic risk, as well as risk of stroke. However, transdermal estrogen with <50 μg/day of estrogen combined with micronized progesterone appears to be the safer choice with respect to thrombotic and stroke risk. Also, vaginal HT administration may play a role in myocardial infarction and stroke risk prevention, but this is based on limited evidence and requires further investigation. The timing of HT initiation and duration may be important factors to consider when prescribing HT especially in women with adverse cardiometabolic profile and pre-existing conditions such as coronary/carotid atherosclerosis, which are at risk of developing, and thus progressing to CVD. The quality of evidence was generally low or moderate and the findings were based mostly on observational data. Use of low-dose oral and transdermal HT appears to be safe with regard to CVD risk in women in menopausal transition and within the first years (e.g. 10 years) after menopause onset. In women with increased baseline thromboembolic risk, alternative non-hormonal medications are suggested as first-line treatment and transdermal estradiol alone or with micronized progesterone only should be considered when these options are not effective. When HT is initiated >10 years since the menopause onset (>60 years old), due to greater absolute risks of coronary heart disease, stroke and venous thromboembolism, HT should be used for the shortest time possible and in lowest possible dose and preferably transdermal administration should be recommended. However, an individualized treatment approach including baseline CVD risk assessment should be applied when prescribing HT. The majority of studies included in the current review are from North American and European populations, which might limit the generalizability of the findings of this review to the other populations. Finally, the quality of evidence included in this review was generally low or moderate, highlighting a need for more rigorous research to help us better understand HT and cardiovascular health.

A8229 Which is better? Comparison of four definitions of childhood elevated blood pressure in predicting subclinical cardiovascular outcomes in adulthood

A8229 Which is better? Comparison of four definitions of childhood elevated blood pressure in predicting subclinical cardiovascular outcomes in adulthood

Short-term effects of physical activity, air pollution and their interaction on the cardiovascular and respiratory system

Physical activity (PA) in urban environments may lead to increased inhalation of air pollutants. As PA and air pollution (AP) have respectively beneficial and detrimental effects on the cardiorespiratory system, the responses to these exposures can interact. Therefore, we assessed the short-term effects of PA, AP and their interaction on a set of subclinical cardiovascular and respiratory outcomes in a panel of healthy adults: heart rate variability (HRV), retinal vessel diameters, lung function and fractional exhaled nitric oxide (FeNO).One hundred twenty two participants measured their PA level and exposure to black carbon (BC), a marker of AP exposure, with wearable sensors during an unscripted week in three different seasons. The study was part of the PASTA project in three European cities (Antwerp: 41 participants, Barcelona: 41 participants, London: 40 participants). At the end of each measurement week, the health outcomes were evaluated. Responses to PA, BC and their interaction were assessed with mixed effect regression models. Separate models were used to account for a 2-h and 24-h time window.During the 2-h time window, HRV and lung function changed statistically significantly in response to PA (METhours) and logarithmic BC (%change). Changes in HRV marked an increased sympathetic tone with both PA (logarithmic LF/HF: +7%; p < 0.01) and BC (logarithmic HF: −19%; p < 0.05). In addition, PA provoked bronchodilation which was illustrated by a significant increase in lung function (FEV1: +15.63 mL; p < 0.05). While a BC %increase was associated with a significant lung function decrease (PEF: −0.10 mL; p < 0.05), the interaction indicated a potential protective effect of PA (p < 0.05). We did not observe a response of the retinal vessel diameters. Most subclinical outcomes did not change in the 24-h time window (except for a few minor changes in LF/HF, FeNO and PEF).Our results on the separate and combined effects of short-term PA and AP exposure on subclinical markers of the cardiorespiratory system are relevant for public health. We provide insights on the physiological responses of multiple, complementary markers. This may move further research towards elucidating potential pathways to disease and the long-term clinical impact of the observed physiological changes.

The relationship between cumulative unfair treatment and intima media thickness and adventitial diameter: The moderating role of race in the study of women's health across the nation.

Unfair treatment may have a detrimental effect on cardiovascular health. However, little research on chronic health outcomes uses cumulative measures of unfair treatment. We tested whether cumulative unfair treatment was associated with greater subclinical cardiovascular disease in a diverse sample of African-American, Caucasian, Chinese, and Hispanic women. We also examined whether this relationship varied by race. The Study of Women's Health Across the Nation is a longitudinal study of midlife women. Cumulative unfair treatment was calculated as the average of unfair treatment assessed over 10 years at 6 time points. Subclinical cardiovascular disease, specifically carotid intima media thickness and adventitial diameter, was assessed via carotid ultrasound conducted at study year 12 in 1,056 women. We tested whether cumulative unfair treatment was related to subclinical cardiovascular disease via linear regression, controlling for demographic factors including socioeconomic status and cardiovascular risk factors. The relation between unfair treatment and subclinical cardiovascular disease significantly varied by race (ps < .05), with unfair treatment related to higher intima media thickness (B = .03, SE = .01, p = .009) and adventitial diameter (B = .02, SE = .009, p = .013) only among Caucasian women. No significant relations between unfair treatment and subclinical cardiovascular disease outcomes were observed for African-American, Hispanic, and Chinese women. Our findings indicate that cumulative unfair treatment is related to worse subclinical cardiovascular disease among Caucasian women. These findings add to the growing literature showing that Caucasian women's experience of unfair treatment may have detrimental health implications. (PsycINFO Database Record

Abstract 12216: Age-Related Macular Degeneration as a Predictor of Incidence and Progression of Subclinical Cardiovascular Disease and Cardiovascular Outcomes: The Multi-Ethnic Study of Atherosclerosis

Introduction: Age-related macular degeneration (AMD) is a leading cause of vision loss in US adults and shares many similarities with CVD pathophysiology. Hypothesis: We assessed the hypothesis that the presence of AMD would independently predict the incidence and progression of subclinical CVD and CVD events in the Multi-Ethnic Study of Atherosclerosis (MESA). Methods: Our cohort consisted of 5,803 adults free of known CVD who had retinal photographs taken during the first follow-up examination of the MESA (Exam 2; Aug 2002-Jan 2004). Photographs were evaluated for AMD using the Wisconsin age-related maculopathy grading system. Coronary artery calcium (CAC), carotid intima-media thickness (cIMT), ankle brachial index (ABI), and brachial artery flow-mediated dilation (FMD) were assessed at baseline (Exam 1; July 2000-Aug 2002). Changes in CAC and cIMT from Exam 1 were determined at follow-up Exam 5 (April 2010-Dec 2011). Incident CVD events were ascertained from 2002 through 2012. Results: Participants were categorized as AMD+ (n = 244) or AMD- (n = 5,559). Groups did not differ at baseline for cIMT, ABI, or FMD (P&gt;0.19). At Exam 5, 92 AMD+ and 2684 AMD- participants had CAC scores. In those with CAC = 0 at baseline, CAC incidence did not differ between AMD+ (n = 21) and AMD- groups (n = 761). In those with CAC&gt;0, CAC progression was greater in the 46 AMD+ vs. the 1170 AMD- participants after a mean follow-up of 10.4 ± 2.4 years using multivariable-adjusted models (530 ± 537 vs. 339 ± 426 Agatston units, P = 0.004). Ten year cIMT progression (P = 0.85) and incident CVD events (multivariable-adjusted HR (95% CI) = 1.3 (0.9, 1.8); P = 0.20) did not differ between groups. Conclusions: In conclusion, the presence of AMD in a diverse population without known CVD was independently associated with higher 10-year CAC progression in participants with baseline CAC&gt;0. AMD was not associated with CAC incidence, other subclinical CVD markers or CVD events. The association between AMD and CAC progression suggests that AMD is associated with a greater degree of atherosclerosis. Longer follow up of individuals with AMD is warranted to clarify whether greater CAC progression increases risk of CVD events.

The Influence of Known Genetic Variants on Subclinical Cardiovascular Outcomes in Childhood: Generation R Study.

Genome-wide association studies have identified single-nucleotide polymorphisms (SNPs) for subclinical cardiovascular outcomes in adults. We examined the influence of these variants on the same outcomes in childhood. In a population-based prospective cohort study among 4137 children, we examined the associations of SNPs, individually and incorporated in genetic risk scores, which were identified in adults for cardiac (2 SNPs for left ventricular end-diastolic diameter and 5 SNPs for aortic root diameter) and blood pressure outcomes (29 SNPs for systolic and diastolic blood pressure, 22 SNPs for mean arterial pressure, and 10 SNPs for pulse pressure) with the same outcomes in children (median age of 6.0 years [95% range, 4.5-8.7]). Weighted and unweighted risk scores for aortic root diameter were associated with childhood aortic root diameter (difference per additional average risk allele 0.09 mm [95% CI: 0.05, 0.13]). Weighted and unweighted risk scores for pulse pressure were associated with childhood pulse pressure (difference per additional average risk allele 0.22 mm Hg [95% CI: 0.08, 0.35] and 0.18 mm Hg [95% CI: 0.05, 0.31], respectively), but not with childhood systolic or diastolic blood pressure or mean arterial pressure. The risk scores for blood pressure and mean arterial pressure were not associated with any of the childhood blood pressure outcomes. Genetic risk scores based on SNPs for aortic root diameter and pulse pressure in adults are associated with the same outcomes in children. SNPs related to cardiovascular outcomes in adulthood at least partly influence cardiovascular development from early life onwards.

Hepatic steatosis and cardiovascular disease outcomes: An analysis of the Framingham Heart Study

Non-alcoholic fatty liver disease (NAFLD) is highly prevalent and is associated with development of metabolic disease including atherosclerotic cardiovascular disease (CVD). Our aim is to examine the association of hepatic steatosis with prevalent clinical and subclinical CVD outcomes in a large community-based sample, the Framingham Heart Study. Hepatic steatosis was measured in 3529 participants using multidetector computed tomography scanning. Multivariable logistic regression was used to determine whether hepatic steatosis is associated with prevalent CVD adjusted for covariates. We also tested whether associations were independent of other metabolic diseases/traits. The primary clinical outcome was composite prevalent clinical CVD defined by prior non-fatal myocardial infarction, stroke, transient ischemic attack, heart failure, or peripheral arterial disease. Subclinical cardiovascular outcomes were coronary artery calcium (CAC) and abdominal artery calcium (AAC). 3014 participants were included (50.5% women). There was a non-significant association of hepatic steatosis with clinical CVD (OR 1.14 [p=0.07]). Hepatic steatosis was associated with both CAC and AAC (OR 1.20 [p<0.001] and OR 1.16 [p<0.001], respectively). Associations persisted for CAC even when controlling for other risk factors/metabolic diseases, but for AAC, the associations became non-significant after adjustment for visceral adipose tissue. The association between hepatic steatosis and AAC was stronger in men than in women (p sex interaction=0.022). There was a significant association of hepatic steatosis with subclinical CVD outcomes independent of many metabolic diseases/traits with a trend towards association between hepatic steatosis and clinical CVD outcomes. The association with AAC was stronger in men than in women.

Homoarginine and cardiovascular outcome in the population-based Dallas Heart Study.

The nonproteinogenic amino acid homoarginine has been postulated to have antiatherosclerotic effects as a weak substrate of nitric oxide synthase. This investigation in the population-based Dallas Heart Study (DHS) aimed to evaluate the association of homoarginine with clinical and subclinical cardiovascular outcomes. Plasma homoarginine was measured in 3514 participants of the DHS using liquid chromatography-tandem mass spectrometry. Associations between homoarginine and major adverse cardiovascular events and all-cause mortality were analyzed using Cox proportional hazard models adjusting for cardiovascular risk factors. Linear regression was used to assess cross-sectional associations between homoarginine and subclinical cardiovascular disease, including coronary artery calcium measured by electron beam-computed tomography, and aortic plaque burden and aortic wall thickness by MRI. Median age was 43 (interquartile range, 36-52) years, with 56% women and 52% black participants. Median follow-up was 9.4 (9.0-9.8) years. Median plasma homoarginine was 2.80 (2.14-3.54) μmol/L. In multivariable models, higher homoarginine was associated with lower rate of major adverse cardiovascular events (hazard ratio, 0.86; 95% confidence interval, 0.75-0.98) and lower all-cause mortality (hazard ratio, 0.82; 0.73-0.92; per 1 log SD increase in homoarginine). Homoarginine was inversely and independently associated with aortic wall thickness (β-estimate, -0.04; P<0.01) but not with aortic plaque burden and coronary artery calcium. Homoarginine is inversely associated with subclinical vascular disease and with risk for cardiovascular disease events. Additional studies are needed to evaluate whether the regulation of plasma homoarginine could emerge as a novel therapeutic option to improve outcomes in cardiovascular disease.