Multi-Ethnic Study Of Atherosclerosis Cohort Research Articles

Abstract 13839: Differences in Prevalence, Incidence, and Progression of Coronary Artery Calcium among Participants With Chronic Kidney Disease With and Without Diabetes Mellitus: Multi-Ethnic Study of Atherosclerosis (MESA)

Introduction: Chronic kidney disease (CKD) is associated with elevated coronary artery calcium (CAC) scores, presumed from altered calcium/phosphorus metabolism. However, differences in prevalence/progression of CAC in CKD with (CKD-DM) and without (CKD-non-DM) diabetes are not known. Methods: The MESA cohort (6780 individuals aged 45-84 yr, with no clinical cardiovascular disease enrolled 2000-02) were followed until 2010-12. Baseline CKD was identified (eGFR<60 ml/min/1.73 m 2 using CKD-EPI creatinine and cystatin C-based eGFR or spot urine albumin/creatinine ≥ 17 mg/g in men; 25 mg/g in women). Prevalent CAC was defined by baseline Agatston score >0, incident CAC by any follow-up Agatston score > 0 in those with baseline CAC=0, and CAC progression by any CAC score increase vs. baseline. CAC progression was adjusted for demographic, clinical and inflammatory biomarker variables using linear regression. Results: 1308 (19.3%) MESA participants had CKD, while 853 (12.5%) had DM. CAC > 0 at baseline was lowest (44.3%) in non-CKD, non-DM, intermediate in those with either condition, and highest (67.1%) in CKD-DM participants (table). CAC incidence (among those with CAC=0 at baseline) was highest in CKD-DM, lowest in non-CKD-non-DM (39.3% vs 18.3%, p<0.0001) & intermediate with either CKD or DM alone (27%). About 90% of those with CAC > 0 at baseline had an increase in Agatston score in follow-up; Agatston score increased 37.0/yr in non-CKD-non-DM, 57.6/yr in CKD-non-DM, 68.3/yr in non-CKD-DM, and 107.6/yr in CKD-DM (all pairwise p<0.001). Extensive adjustment (table) attenuated to similar increases between non-CKD-non-DM and CKD-non-DM (40.6 vs 47.2/yr, p=0.09). Greater increases remained in non-CKD-DM (65.7/yr) and in CKD-DM (95.8/yr, p<0.002). Conclusion: CKD-non-DM participants had slower CAC incidence/progression compared to CKD-DM participants. CAC differences among CKD participants may help identify subgroups at higher risk of future events.

The Impact of Neighborhoods on CV Risk.

Cardiovascular disease (CVD) continues to be the leading cause of death and a major source of health disparities in the Unites States and globally. Efforts to reduce CVD risk and eliminate cardiovascular health disparities have increasingly emphasized the importance of the social determinants of health. Neighborhood environments have emerged as a possible target for prevention and policy efforts. Hence there is a need to better understand the role of neighborhood environments in shaping cardiovascular risk. The MESA (Multi-Ethnic Study of Atherosclerosis) Neighborhood Study provided a unique opportunity to build a comprehensive place-based resource for investigations of associations between specific features of neighborhood physical and social environments and cardiovascular risk factors and outcomes. This review summarizes the approaches used to characterize residential neighborhood environments in the MESA cohort, provides an overview of key findings to date, and discusses challenges and opportunities in neighborhood health effects research. Results to date suggest that neighborhood physical and social environments are related to behavioral and biomedical risk factors for CVD and that cardiovascular prevention efforts may benefit from taking neighborhood context into account.

Cardiac Magnetic Resonance-Measured Left Atrial Volume and Function and Incident Atrial Fibrillation: Results From MESA (Multi-Ethnic Study of Atherosclerosis).

Early detection of structural changes in left atrium (LA) before atrial fibrillation (AF) development could be helpful in identification of those at higher risk for AF. Using cardiac magnetic resonance imaging, we examined the association of LA volume and function, and incident AF in a multiethnic population free of clinical cardiovascular diseases. In a case-cohort study embedded in MESA (Multi-Ethnic Study of Atherosclerosis), baseline LA size and function assessed by cardiac magnetic resonance feature-tracking were compared between 197 participants with incident AF and 322 participants randomly selected from the whole MESA cohort. Participants were followed up for 8 years. Incident AF cases had a larger LA volume and decreased passive, active, and total LA emptying fractions and peak global LA longitudinal strain (peak LA strain) at baseline. In multivariable analysis, elevated LA maximum volume index (hazard ratio, 1.38 per SD; 95% confidence interval, 1.01-1.89) and decreased peak LA strain (hazard ratio, 0.68 per SD; 95% confidence interval, 0.48-0.96), and passive and total LA emptying fractions (hazard ratio for passive LA emptying fractions, 0.55 per SD; 95% confidence interval, 0.40-0.75 and hazard ratio for active LA emptying fractions, 0.70 per SD; 95% confidence interval, 0.52-0.95), but not active LA emptying fraction, were associated with incident AF. Elevated LA volumes and decreased passive and total LA emptying fractions were independently associated with incident AF in an asymptomatic multiethnic population. Including LA functional variables along with other risk factors of AF may help to better risk stratify individuals at risk of AF development.

The association of calcium supplementation and incident cardiovascular events in the Multi-ethnic Study of Atherosclerosis (MESA)

Background and aimsMany US adults use calcium supplements to address inadequate dietary intake and improve bone health. However, recent reports have suggested that use of calcium supplements may elevate cardiovascular disease (CVD) risk. In this study, we examined associations between baseline calcium supplement use and incident myocardial infarction (MI) (n = 208 events) and CVD events (n = 641 events) over 10.3 years in men and women from the Multi-Ethnic Study of Atherosclerosis (MESA) cohort (n = 6236), with dietary calcium intake at baseline also examined as a supplementary objective. Methods and resultsUsing Cox proportional hazards models, no compelling associations between calcium intake from supplements or diet and incident CVD events were observed upon multivariate adjustment for potential confounders. An association with lower MI risk was observed comparing those with low levels of calcium supplement use (1–499 mg) to those using no calcium supplements (hazard ratio 0.69, 95% CI 0.48, 0.98, p = 0.039). Relationships were homogeneous by gender, race/ethnicity, or chronic kidney disease. Results were also similar when the analysis was limited to postmenopausal women only. ConclusionAnalysis of incident MI and CVD events in the MESA cohort does not support a substantial association of calcium supplement use with negative cardiovascular outcomes.

Reference ranges for short-term heart rate variability measures in individuals free of cardiovascular disease: The Multi-Ethnic Study of Atherosclerosis (MESA)

BackgroundNormative values for heart rate variability (HRV) measures from 10-s electrocardiograms (ECG) have not been defined. MethodsWe reported borderline abnormal (<5th percentile) and abnormal (<2nd percentile) values of standard deviation of all normal-to-normal R-R intervals (SDNN) and root mean square of successive differences between normal-to-normal R-R intervals (rMSSD) from 10-s ECGs in 1175 participants (mean age=59±10; 59% female; 47% white) ≥45years of age from the Multi-Ethnic Study of Atherosclerosis (MESA) who were free of cardiovascular disease (CVD) and CVD risk factors. We validated the prognostic significance of these measures in a subset of the MESA cohort with complete data. ResultsBorderline abnormal and abnormal SDNN and rMSSD varied by sex and race. Borderline abnormal and abnormal SDNN and rMSSD were associated with an increased risk of CVD and all-cause mortality. ConclusionsThe references ranges provided in this report will guide future research using these common HRV parameters.

Prediction of fine particulate matter chemical components with a spatio-temporal model for the Multi-Ethnic Study of Atherosclerosis cohort.

Although cohort studies of the health effects of PM2.5 have developed exposure prediction models to represent spatial variability across participant residences, few models exist for PM2.5 components. We aimed to develop a city-specific spatio-temporal prediction approach to estimate long-term average concentrations of four PM2.5 components including sulfur, silicon, and elemental and organic carbon for the Multi-Ethnic Study of Atherosclerosis cohort, and to compare predictions to those from a national spatial model. Using 2-week average measurements from a cohort-focused monitoring campaign, the spatio-temporal model employed selected geographic covariates in a universal kriging framework with the data-driven temporal trend. Relying on long-term means of daily measurements from regulatory monitoring networks, the national spatial model employed dimension-reduced predictors using universal kriging. For the spatio-temporal model, the cross-validated and temporally-adjusted R(2) was relatively higher for EC and OC, and in the Los Angeles and Baltimore areas. The cross-validated R(2)s for both models across the six areas were reasonably high for all components except silicon. Predicted long-term concentrations at participant homes from the two models were generally highly correlated across cities but poorly correlated within cities. The spatio-temporal model may be preferred for city-specific health analyses, whereas both models could be used for multi-city studies.

Effect of Physical Activity on the Relation Between Psychosocial Factors and Cardiovascular Events (from the Multi-Ethnic Study of Atherosclerosis)

Depression, chronic stress, and low levels of social support have known associations with cardiovascular disease (CVD). Physical activity has been shown to promote psychological health, reduce the frequency of depressive symptoms, and is associated with fewer cardiovascular events in depressed subjects with known CVD. The purpose of the present study was to test the hypothesis that physical activity attenuates the association between psychosocial factors and incident CVD. The Multi-Ethnic Study of Atherosclerosis cohort includes 6,814 participants free of clinical CVD at baseline. Complete data on physical activity were available for 6,795 subjects (mean age 62years; 47% men). Psychosocial factors were assessed using standardized questionnaires. Cox proportional hazard models were used to evaluate the association between psychosocial factors and CVD events and its modulation by physical activity. In models adjusted for age, gender, and race/ethnicity, both depression and chronic burden were associated with CVD events (hazard ratio [HR]= 1.38 [1.04 to 1.84], p= 0.028 for depression; HR= 1.15 [1.05 to 1.24], p= 0.001 for chronic burden). Adjusting for physical activity, the relation between depression, chronic burden, and CVD events was not significantly reduced (HR= 1.35 [1.02 to 1.80], p= 0.039 for depression; HR= 1.14 [1.05 to 1.23], p= 0.001 for chronic burden). Although physical activity is an important component of physical and psychological healthand well-being, it did not significantly attenuate the strong relation between depression orchronic burden and incident CVD.

Abstract 44: Association of Somatic and Affective Factors with Inflammation: The Multi-Ethnic Study of Atherosclerosis (MESA)

Objective: Proinflamatory biomarkers such as C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) have been linked to the pathophysiology of depression. Depressive states encompass affective (both negative &amp; positive affect) and somatic symptoms. The association of affective and somatic factors of depression with inflammation has not been examined in a multi-ethnic cohort. Methods: Data were derived from 6,818 participants aged 45-84 years from the Multi-Ethnic Study of Atherosclerosis (MESA).Depressive symptoms, as measured by the Center for Epidemiologic Studies Depression Scale (CES-D), and inflammatory markers (i.e., CRP, IL-6 and TNF-α) were collected from visit 1 from the MESA cohort. Inflammatory markers were log-transformed to reduce skewness. A confirmatory factor analysis supported a 3-factor model of the CES-D comprised of: somatic symptoms (poor appetite, could not get going, poor sleep, excessive effort, trouble concentrating), negative affect (feeling blue, depressed, crying spells, sadness, felt like a failure, fearful and lonely), and positive affect (feeling happy, good, hopeful, enjoy life). In cross-sectional analyses, structural equation modeling (SEM) was performed to examine the associations between affective and somatic latent variables of the CES-D with the inflammatory biomarkers (CRP, IL-6 and TNF-α) after controlling for age, gender, ethnicity, BMI, lipids, systolic blood pressure, smoking, alcohol use, physical activity, diabetes, lipid-lowering medications and antihypertensives. Results: The mean age was 62.15 (SD=1.23) and mean CES-D score was 7.57 (SD=7.59). The 3-factor model of the CES-D exhibited good fit with root mean square-error of approximation &lt;0.05 and standardized root mean square residual &lt;0.07. In the fully adjusted models, the SEM showed a significant association between the somatic factor and IL-6 (β=0.18;p&lt;0.01)and TNF-α (β=0.21;p=0.006) but not CRP (β=-0.12; p=0.16). The negative affect factor was significantly associated with IL-6 (β=0.05;p=0.006), CRP (β=0.04; p=0.03) but not with TNF-α (β=-0.02;p=0.18), while the positive factor was significantly associated with IL-6 (β=0.20;p=0.006), CRP (β=0.65;p&lt;0.001) and TNF-α (β=-0.17;p=0.01). Conclusion: This cross-sectional study showed that inflammatory markers are significantly associated with somatic and both positive and affective factors of depressive symptomatology in a multi-ethnic cohort.

Data on coronary artery calcium score performance and cardiovascular risk reclassification across gender and ethnicities

The current guidelines recommend the new risk score, Atherosclerotic Cardiovascular Disease score (ASCVD), to assess an individual׳s risk of future cardiovascular disease (CVD) events. No data exist on the predictive utility of ASCVD score with the incremental value of coronary artery calcium scoring (CACS) across ethnicities and gender. Multi-Ethnic Study of Atherosclerosis (MESA) is a population based study (n=6814) of White (38%), Black (28%), Chinese (22%) and Hispanic (12%) subjects, aged 45–84 years, free from clinical cardiovascular disease. We performed a post-hoc analysis of 6742 participants (mean age 62, 53% female) from the MESA cohort. We evaluated the predictive accuracy for the ASCVD score for each participant in accord with the American College of Cardiology/American Heart Association guidelines using pooled cohort equations. Similar to the publication by Fudim et al. “The Metabolic Syndrome, Coronary Artery Calcium Score and Cardiovascular Risk Reclassification” [1] the analytic properties of models incorporating the ASCVD score with and without CACS were compared for cardiovascular disease CVD prediction. Here the analysis focused on ASCVD score (with and without CACS) performance across gender and ethnicities.

Abstract 10983: Alcohol Intake and Heart Failure Incidence: Results From the Multi-Ethnic Study of Atherosclerosis (MESA)

Background: Alcohol intake has a well-described J-shaped effect on cardiovascular disease and all-cause mortality. Previous studies have shown a lower incidence of heart failure (HF) with moderate alcohol use. However, it is unknown whether alcohol intake is associated with a lower incidence of HF with reduced ejection fraction (HFrEF) or with preserved ejection fraction (HFpEF). Methods: We performed analyses of participants from the Multi-Ethnic Study of Atherosclerosis (MESA) to assess the association of alcohol and incident HF. Alcohol use was determine by self-report at baseline. Individuals were free of cardiovascular disease at baseline and were followed for a mean of 10.2 ± 2.8 years for incident events. Heart failure was classified as HFrEF (ejection fraction (EF) ≤50%) or HFpEF (EF &gt; 50%) at the time of HF diagnosis. We performed time-fixed Cox proportional hazard regression models to assess associations between alcohol use and incident heart failure. Analyses were adjusted for age, sex, race, smoking (pack-years), and education, and then additionally for systolic and diastolic blood pressures, use of antihypertensive medications, family history of CHD, diabetes, HDL-cholesterol, C-reactive protein, fibrinogen, and interim myocardial infarction as a time-varying covariate. Results: We identified 6,763 individuals with alcohol use data, which included 1,390 (20.6%) never, 1,624 (24.0%) former, and 3,749 (55.4%) current drinkers at baseline. The average age was 62.1 years with 47.2% men. There were 258 HF events with 118 classified as HFrEF, 112 as HFpEF, and 28 participants excluded from analyses due to an unknown EF. Compared to never drinkers, individuals reporting &gt; 2 drinks per day had a higher risk of developing HFpEF [HR 2.41 (95% CI 1.04, 5.60) in model 1 and HR: 2.65 (1.10-6.42) in the fully adjusted model]. There were no significant associations between alcohol use and incident overall HF (HFpEF and HFrEF combined) [HR 1.31 (0.73-2.35)] or HFrEF [HR 0.78 (0.32-1.92)]. Conclusion: In the MESA cohort, individuals who drank greater than 2 alcoholic drinks per day had an increased odds of incident HFpEF but not HFrEF. Follow-up studies are needed to understand the etiology of these differences and to investigate for differences by race and sex.

Visual Impairment in White, Chinese, Black, and Hispanic Participants from the Multi-Ethnic Study of Atherosclerosis Cohort

Purpose: To describe the prevalence of visual impairment and examine its association with demographic, socioeconomic, and health characteristics in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort.Methods: Visual acuity data were obtained from 6134 participants, aged 46–87 years at time of examination between 2002 and 2004 (mean age 64 years, 47.6% male), from six communities in the United States. Visual impairment was defined as presenting visual acuity 20/50 or worse in the better-seeing eye. Risk factors were included in multivariable logistic regression models to determine their impact on visual impairment for men and women in each racial/ethnic group.Results: Among all participants, 6.6% (n = 421) had visual impairment, including 5.6% of men (n = 178) and 7.5% of women (n = 243). Prevalence of impairment ranged from 4.2% (n = 52) and 6.0% (n = 77) in white men and women, respectively, to 7.6% (n = 37) and 11.6% (n = 44) in Chinese men and women, respectively. Older age was significantly associated with visual impairment in both men and women, particularly in those with lower socioeconomic status, but the effects of increasing age were more pronounced in men. Two-thirds of participants already wore distance correction, and not unexpectedly, a lower prevalence of visual impairment was seen in this group; however, 2.4% of men and 3.5% of women with current distance correction had correctable visual impairment, most notably among seniors.Conclusion: Even in the U.S. where prevalence of refractive correction is high, both visual impairment and uncorrected refractive error represent current public health challenges.

Computing a Synthetic Chronic Psychosocial Stress Measurement in Multiple Datasets and its Application in the Replication of G × E Interactions of the EBF1 Gene.

Chronic psychosocial stress adversely affects health and is associated with the development of disease [Williams, 2008]. Systematic epidemiological and genetic studies are needed to uncover genetic variants that interact with stress to modify metabolic responses across the life cycle that are the proximal contributors to the development of cardiovascular disease and precipitation of acute clinical events. Among the central challenges in the field are to perform and replicate gene-by-environment (G × E) studies. The challenge of measurement of individual experience of psychosocial stress is magnified in this context. Although many research datasets exist that contain genotyping and disease-related data, measures of psychosocial stress are often either absent or vary substantially across studies. In this paper, we provide an algorithm to create a synthetic measure of chronic psychosocial stress across multiple datasets, applying a consistent criterion that uses proxy indicators of stress components. We validated the computed scores of chronic psychosocial stress by observing moderately strong and significant correlations with the self-rated chronic psychosocial stress in the Multi-Ethnic Study of Atherosclerosis Cohort (Rho = 0.23, P < 0.0001) and with the measures of depressive symptoms in five datasets (Rho = 0.15-0.42, Ps = 0.005 to <0.0001) and by comparing the distributions of the self-rated and computed measures. Finally, we demonstrate the utility of this computed chronic psychosocial stress variable by providing three additional replications of our previous finding of gene-by-stress interaction with central obesity traits [Singh et al., 2015].

Association of subclinical atherosclerosis using carotid intima-media thickness, carotid plaque, and coronary calcium score with left ventricular dyssynchrony: The multi-ethnic Study of Atherosclerosis

BackgroundThe role of atherosclerosis in the progression of global left ventricular dysfunction and cardiovascular events has been well recognized. Left ventricular (LV) dyssynchrony is a measure of regional myocardial dysfunction. Our objective was to investigate the relationship of subclinical atherosclerosis with mechanical LV dyssynchrony in a population-based asymptomatic multi-ethnic cohort. Methods and ResultsParticipants of the Multi-Ethnic Study of Atherosclerosis (MESA) at exam 5 were evaluated using 1.5T cardiac magnetic resonance (CMR) imaging, carotid ultrasound (n = 2062) for common carotid artery (CCA) and internal carotid artery (ICA) intima-media thickness (IMT), and cardiac computed tomography (n = 2039) for coronary artery calcium (CAC) assessment (Agatston method). Dyssynchrony indices were defined as the standard deviation of time to peak systolic circumferential strain (SD-TPS) and the difference between maximum and minimum (max-min) time to peak strain using harmonic phase imaging in 12 segments (3-slices × 4 segments). Multivariable regression analyses were performed to assess associations after adjusting for participant demographics, cardiovascular risk factors, LV mass, and ejection fraction. In multivariable analyses, SD-TPS was significantly related to measures of atherosclerosis, including CCA-IMT (8.7 ms/mm change in IMT, p = 0.020), ICA-IMT (19.2 ms/mm change in IMT, p < 0.001), carotid plaque score (1.2 ms/unit change in score, p < 0.001), and log transformed CAC+1 (0.66 ms/unit log-CAC+1, p = 0.018). These findings were consistent with other parameter of LV dyssynchrony i.e. max–min. ConclusionIn the MESA cohort, measures of atherosclerosis are associated with parameters of subclinical LV dyssynchrony in the absence of clinical coronary event and left-bundle-branch block.

Is Sickle Cell Trait Associated with Incident Cardiovascular Outcomes in African Americans?

BackgroundAfrican Americans experience higher rates of cardiovascular disease (CVD) and mortality from stroke and coronary heart disease. It is possible that genetic modifiers associated with African ancestry may confer higher risk of CVD. The sickle cell mutation results from a functional single nucleotide polymorphism (SNP) involving the substitution of GTG (valine) for a GAG (glutamic acid) in the gene encoding beta globin. Heterozygosity for the mutation (rs334) results in sickle cell trait (SCT) which is prevalent among 8% of African Americans, while homozygosity produces sickle cell anemia. Sickle cell trait has been deemed clinically benign yet recent evidence shows that it is associated with increased risk of chronic kidney disease, a 2 times increased risk for venous thromboembolism and a 4 times increased risk for pulmonary embolism. Further, there is evidence that individuals with SCT have higher serum levels of C-reactive protein, Fibrinogen 2.1 fragments and D-dimers. We hypothesized that African Americans with SCT have a higher risk for cardiovascular outcomes than those without SCT (homozygous wild-type hemoglobin).MethodsData were obtained from the Multi-Ethnic Study of Atherosclerosis (MESA), Jackson Heart Study (JHS) and Women’s Health Initiative (WHI). Incident myocardial infarction (MI) was defined as adjudicated non-fatal or fatal MI, coronary heart disease (CHD) was defined as a composite endpoint including adjudicated non-fatal MI, fatal CHD, or documented coronary revascularization procedure. Sickle cell trait was identified either by direct genotyping or imputation for rs334. Individuals who were homozygous for the sickle mutation or had a prior history of CHD events were excluded. Cox proportional hazards models were used to estimate a hazard ratio (HR) of incident MI or CHD comparing sickle cell trait carriers to non-carriers. Models were adjusted for age, sex and principal component of global ancestry. Analysis was performed separately in each cohort and the results were subsequently meta-analyzed using a fixed effect inverse variance weighted method.ResultsA total of 11,128 African American men and women were included in the pooled data base. The average age at baseline were 62.2 ± 10.1, 49.8 ± 11.8 and 61.4 ± 7.0 years for MESA, JHS and WHI respectively, with JHS participants significantly younger than the other two cohorts (p <0.001). Unlike the MESA and JHS cohorts that included both genders, the WHI cohort was exclusively female. Additionally, the percentage African ancestry was significantly higher among those with SCT compared to those without SCT (82 ± 12% vs. 78 ± 14% for MESA, 84 ± 6% vs. 82 ± 9% for JHS and 79 ± 12% vs. 76 ± 15% for WHI), further the percentage African ancestry was significantly lower among WHI subjects irrespective of carrier status, p <0.01. There was no significant difference between cohorts in the prevalence of diabetes or hypertension, mean blood pressure levels, or proportion of smokers (table 1). The HR for incident MI was 1.56 (0.66 – 3.68) in MESA, 1.04 (0.32 – 3.39) in JHS and 0.97 (0.68 – 1.39) in WHI, but was not statistically significant. Further, the HR for incident CHD was 2.73 (1.52 – 4.89) in MESA, 1.14 (0.46 – 2.89) in JHS and 0.97 (0.68 – 1.17) in WHI, although the HR only achieved statistical significance in MESA (p<0.001). Overall, sickle cell trait was not significantly associated with incident MI (1.04 [0.76 – 1.43]) or CHD (1.11 [0.85 – 1.43] figure 1).Limitation/Recommendations and ConclusionThe overall result from this study did not demonstrate a significant association between SCT and CHD. This may reflect inadequate power due to the relatively small number of CHD events and differences in study design. This study suggests the need for a well powered study to test this hypothesis, the result of which could have significant impact on the approach to risk factor modification for African Americans. [Display omitted] [Display omitted] DisclosuresNaik:NHLBI: Research Funding.

Atrial fibrillation incidence and risk factors in relation to race-ethnicity and the population attributable fraction of atrial fibrillation risk factors: the Multi-Ethnic Study of Atherosclerosis

PurposeWe studied incident atrial fibrillation (AF) in the prospective community-based Multi-Ethnic Study of Atherosclerosis (MESA). Reportedly, non-Hispanic blacks (NHBs) have a lower AF burden compared with their non-Hispanic white (NHW) counterparts. Information on the epidemiology of AF in Hispanic and Asian populations is much more limited. MethodsWe excluded participants with a history of AF at enrollment. A total of 6721 MESA participants were monitored for the first AF event ascertained according to hospital discharge International Classification of Diseases, Ninth Revision, codes. Age- and sex-adjusted incidence rates (IRs) of AF were calculated per 1000 person-years of observation. IR ratios were calculated using NHWs as the reference group. Age- and sex-adjusted population attributable fractions (PAFs) of established modifiable AF risk factors were ascertained. ResultsIn the MESA cohort, 47.2% was male; at baseline, 25.7% had hypertension; 12.5% had diabetes. Three hundred five incident hospitalized AF events occurred over a mean follow-up of 7.3 years. Age- and sex-adjusted IRs and IR ratios showed that overall AF incidence was significantly lower among Hispanics, NHBs and Chinese compared with NHWs (all P < .001). Among participants 65 years of age or greater, Hispanics, Chinese, and blacks had significantly lower AF incidence than NHWs (all P ≤ .01), but IRs were similar among participants under age 65 years. The PAF for smoking was 27% among NHBs but lower among other race–ethnic groups. Among NHWs, the PAF for hypertension was 22.2%, but this was higher among NHBs (33.1%), Chinese (46.3%), and Hispanics (43.9%). ConclusionsOverall, the incidence of hospitalized AF was significantly lower in Hispanics, NHBs, and Chinese than in NHWs. A larger proportion of AF events appear to be attributable to hypertension among nonwhite populations compared with NHWs.

Clinical Implications

HomeHypertensionVol. 64, No. 5Clinical Implications Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUBClinical Implications Originally published1 Nov 2014https://doi.org/10.1161/HYPERTENSIONAHA.114.04612Hypertension. 2014;64:905Reflection Magnitude and Death (page 958)Although the systolic and diastolic blood pressures contain important prognostic information, further knowledge can still be gained from analysis of the arterial waveform. Wave reflections, returning to the heart from the periphery in late systole, affect the central pressure waveform and increase the load on the left ventricle. In this study, we performed wave separation analysis on 5984 healthy individuals from the Multi-Ethnic Study of Atherosclerosis cohort and determined the magnitude of the forward (Pf) and backward-traveling (Pb) waves using a physiological flow approach. We found that their ratio (reflection magnitude, Pb/Pf) related to mortality, even after adjustment for traditional atherosclerotic risk factors and blood pressure. Importantly, the forward and backward waves were associated with mortality in opposite directions, with increased backward wave but decreased forward wave amplitude, associating with increased mortality. These relationships were strongest for cardiovascular death. In summary, the arterial waveform provides important incremental information beyond its peak and trough. Both the magnitudes of the forward and backward waves demonstrate significant prognostic relationships to mortality.Download figureDownload PowerPointCD8+ T cells and Hypertension (page 1108)Recent studies have implicated a role of T cells in the genesis of hypertension; however, mechanisms underlying T cell activation in this disease remain poorly defined. Naïve T cells develop in the thymus and migrate to secondary lymphoid organs, including the spleen and lymph nodes. The Vβ region of the T cell receptor gene exhibits enormous diversity, providing recognition of virtually any foreign peptide. Antigen presentation leads to expansion of T cell clones that are specific for individual antigens. In this study, we found that hypertension is associated with expansion of 3 Vβ subtypes in CD8+ T cells of the kidney. We further found that mice lacking CD8+ T cells develop blunted hypertension, as did mice with only 1 T cell receptor specific for an albumin peptide (OT1xRAG-1−/− mice, see Figure). In normal mice and mice lacking CD4+ T cells, we found that hypertension is associated with attenuation of the renal microvasculature and that CD8−/− mice are protected against this vascular perturbation. In another recent study, we identified isoketal-modified proteins as potential neoantigens in hypertension. Isoketals are oxidized products of arachidonic acid that rapidly ligate to proteins. Taken together with our present article in Hypertension, our data indicate that renal oxidative injury leads to formation of oxidatively modified proteins that are recognized as nonself and lead to an oligoclonal population of CD8+ T cells. Efforts to scavenge isoketals or reduce their formation will likely be effective in reducing inflammation, reducing renal injury, and lowering blood pressure.Download figureDownload PowerPointBlood Pressure Control in Uninsured Adults (page 997)Hypertension control in the United States is generally better in white than in black and Hispanic adults. However, all 3 race/ethnicity groups experienced significant and similar absolute percentage improvements in hypertension control between 1988 and 2008. Several reports documented lower hypertension control in uninsured and insured adults at various time points. We were concerned that uninsured individuals might be falling further behind insured adults in hypertension control. Although anticipating the gap in hypertension control between the insured and uninsured might increase, the absence of progress in the uninsured from 1988 to 2010 was unexpected (Figure). Yet during this time period, the age gap in hypertension control, with better control in younger than in older adults, was essentially eliminated.Download figureDownload PowerPointThe uninsured have lower incomes and less education than the insured, which may contribute to disparate hypertension control. Hypertension control was similar among privately and publicly insured adults from 1988 to 2010 (Figure), although education and income were similar in publicly insured and uninsured adults. Thus, insurance emerges as a major factor in hypertension control. The uninsured had fewer healthcare visits, were less aware of hypertension, and less likely to be treated when aware and controlled when treated. Despite the Affordable Care Act, 31 million Americans are likely to remain uninsured. It is important to overcome access barriers to evidence-based care and medications to translate proven benefits of hypertension control to currently uninsured adults. Previous Back to top Next FiguresReferencesRelatedDetails November 2014Vol 64, Issue 5 Advertisement Article InformationMetrics © 2014 American Heart Association, Inc.https://doi.org/10.1161/HYPERTENSIONAHA.114.04612 Originally publishedNovember 1, 2014 PDF download Advertisement

FGF23: more a matter of the heart than of the vessels?

In 2008, Gutierrez et al. [1] were the first to demonstrate a very powerful association between FGF23 serum levels and mortality in incident dialysis patients. Meanwhile, the same relationships were confirmed in prevalent dialysis patients, in CKD patients not on dialysis and even in patients with normal renal function [2–5], and to our knowledge no published report has failed to observe FGF23 as a significant risk predictor for hard outcomes including all-cause and cardiovascular mortality or cardiovascular morbidity. Given these uniform associations, the question has arisen, whether FGF23 levels may just reflect the toxicity of phosphate overload in these patient cohorts, or whether FGF23 may harm cardiovascular tissues by intrinsic mechanisms yet to be detailed—Myles Wolf coined the term of FGF23-related ‘collateral damage’ in this context [6]. In their seminal paper in 2011, Faul et al. [7] demonstrated that intravenous and intramyocardial injections of FGF23 injections led to left ventricular hypertrophy (LVH) in rats. Moreover, they chose the classical CKD rat model of 5/6nephrectomy with the consecutive phenotype of secondary hyperparathyroidism, hyperphosphatemia and hypertension in order to show that despite no change in this ‘clinical’ phenotype the sole administration of a FGF-receptor blocker could fully prevent the development of LVH in this model. While LVH in these experimental settings was found not to be klotho-dependent, it was instead shown that the calcineurinNFAT pathway was instrumental in this cardiac FGF-receptor signalling. Several reports also focused on FGF23-associated reactivity and remodelling of the arterial vasculature. Studies in in vitro and in vivo models as well as in humans [8–11] have demonstrated that both phosphate and FGF23 blunt endothelial function. For example, Mirza et al. [11] found a significant association of FGF23 serum levels with impaired vasoreactivity and increased arterial stiffness in a community-based cohort of subjects aged above 70 (n = 967). More recently, a couple of studies evaluated the potential direct impact of FGF23 on vascular calcification processes. Jimbo et al. [12] used both intact aortic rings obtained from uraemic rats and vascular smooth muscle cells in vitro to address this question. Here, FGF23 acted synergistically on the acceleration of phosphate-induced calcification. This effect was shown to be dependent on local expression of klotho in the vessel wall and on activation of the signal transduction pathway ERK1/2. However, in another similar experimental set-up plus in a subcohort of the Chronic Renal Insufficiency Cohort (CRIC) study (n = 1501 CKD patients) no relationships between the occurrence of vascular calcifications and FGF23 levels could be confirmed [13]. This latter setting, however, did rule out intravascular klotho expression, so the question remains under which conditions arterial vessels express klotho, or whether the detection of klotho in the experiments by Jimbo et al. was immanently limited to their individual study design. Hsu et al. [14] now provide data on the association of FGF23 with relevant surrogates of vascular function in a large patient sample of the Multi-Ethnic Study of Atherosclerosis (MESA) study cohort (n = 5977 patients). The MESA study was initiated in July 2000 to investigate the prevalence, correlates and progression of subclinical cardiovascular disease in a populationbased sample of subjects aged 45–84 years, the majority of whom presented with normal renal function [15]. Readouts of vascular reactivity were large (LAE) and small artery elasticity (SAE) measured by pulse contour analysis of the radial artery, pulse pressure measured with an automated sphygmomanometer, and ankle brachial index (ABI) calculated as the ratio of the ankle and brachial systolic blood pressures. In essence, no associations with arterial stiffness, as measured by pulse pressure, LAE, SAE, or high ABI were demonstrated in this population, confirming previous results by Scialla et al. and Lindberg et al. [13, 16]. Why are these data of importance? Firstly, the MESA study presents by far the largest and best defined study cohort evaluated in this context. Secondly, multiple measures of vascular reactivity were performed which have been proven valuable as independent predictors of outcome in this MESA cohort. However, these results must still leave open the question of whether FGF23 impacts on vascular reactivity and function in patients with advanced CKD, especially because the absolute range of FGF23 in this predominantly normal population was magnitudes below those levels reached in renal failure. IN F O C U S

Significance of a Positive Family History for Coronary Heart Disease in Patients With a Zero Coronary Artery Calcium Score (from the Multi-Ethnic Study of Atherosclerosis)

Although a coronary artery calcium (CAC) score of 0 is associated with a very low 10-year risk for cardiac events, this risk is nonzero. Subjects with a family history of coronary heart disease (CHD) has been associated with more subclinical atherosclerosis than subjects without a family history of CHD. The purpose of this study was to assess the significance of a family history for CHD in subjects with a CAC score of 0. The Multi-Ethnic Study of Atherosclerosis cohort includes 6,814 participants free of clinical cardiovascular disease (CVD) at baseline. Positive family history was defined as reporting a parent, sibling, or child who had a heart attack. Time to incident CHD or CVD event was modeled using the multivariable Cox regression; 3,185 subjects were identified from the original Multi-Ethnic Study of Atherosclerosis cohort as having a baseline CAC score of 0 (mean age 58 years, 37% men). Over a median follow-up of 10 years, 101 participants (3.2%) had CVD events and 56 (1.8%) had CHD events. In age- and gender-adjusted analyses, a family history of CHD was associated with an ∼70% increase in CVD (hazard ratio 1.73, 95% confidence interval 1.17 to 2.56) and CHD (hazard ratio 1.72, 95% confidence interval 1.01 to 2.91) events. CVD events remained significant after further adjustment for ethnicity, risk factors, and baseline medication use. In conclusion, asymptomatic subjects with a 0 CAC score and a positive family history of CHD are at increased risk for CVD and CHD events compared with those without a family history of CHD, although absolute event rates remain low.

Relation of Thoracic Aortic Distensibility to Left Ventricular Area (from the Multi-Ethnic Study of Atherosclerosis [MESA

Decreased arterial compliance is an early manifestation of adverse structural and functional changes within the vessel wall. Its correlation with left ventricular (LV) area on computed tomography, a marker of LV remodeling, has not been well demonstrated. The aim of this study was to test the hypothesis that decreasing aortic compliance and increasing arterial stiffness are independently associated with increased LV area. The study population consisted of 3,540 patients (mean age 61 ± 10 years, 46% men) from the Multi-Ethnic Study of Atherosclerosis (MESA) who underwent aortic distensibility (AD) assessment on magnetic resonance imaging and LV area measurement on computed tomography (adjusted to body surface area). Multivariate logistic regression was performed to assess the association between body surface area-normalized LV area >75th percentile and AD after adjusting for baseline clinical, historical, and imaging covariates. Mean LV area index was 2,153 cm(2), and mean AD was 1.84 × 10(3) mm Hg(-1). Subjects in the lowest AD quartile were older, with higher prevalence rates of hypertension, diabetes, and hypercholesterolemia (p <0.05 for all comparisons). Using multivariate linear regression adjusting for demographics, traditional risk factors, coronary artery calcium, and C-reactive protein, each SD decrease was associated with an 18-cm(2) increase in LV area. In addition, decreasing AD quartiles were independently associated with increasing LV area index, defined as >75th percentile. In conclusion, in this multiethnic cohort, reduced AD was associated with increased LV area. Longitudinal studies are needed to determine if decreased distensibility precedes and directly influences increased LV area.

Evaluation of Age-Related Interstitial Myocardial Fibrosis With Cardiac Magnetic Resonance Contrast-Enhanced T1 Mapping: MESA (Multi-Ethnic Study of Atherosclerosis)

This study sought to determine the relationship of cardiovascular magnetic resonance (CMR) measures of tissue composition to age in the Multi-Ethnic Study of Atherosclerosis (MESA).Animal and human studies have demonstrated increased collagen deposition in senescent hearts. New CMR indices of tissue composition by using T1 mapping are sensitive to the presence of myocardial fibrosis.A total of 1,231 study participants (51% women; age range 54 to 93 years) of the MESA cohort were evaluated with T1 mapping by using 1.5-T CMR scanners. None of the participants had focal scar on delayed enhancement CMR. Single-slice T1 mapping was performed at the midventricular level before and at 12- and 25-min delay after administration of gadolinium contrast by using a modified Look-Locker inversion recovery sequence. The partition coefficient was determined by the slope of the linear relationship of (1/T1myo vs. 1/T1blood). The extracellular volume fraction (ECV) was derived accounting for the hematocrit level. Multivariable regression analyses were performed, adjusting for traditional risk factors and left ventricular structure.Women had significantly greater partition coefficient, ECV, and precontrast T1 than men, as well as lower post-contrast T1 values (all p < 0.05). In general, linear regression analyses demonstrated that greater partition coefficient, pre-contrast T1 values, and ECV were associated with older age in men (multivariate regression coefficients = 0.01; 5.9 ms; and 1.04% per 10 years' change; all p < 0.05). ECV was also significantly associated with age in women after multivariable adjustments.CMR parameters that have been associated with myocardial fibrosis were related to older age in the MESA study. Women had higher ECV than men but less ECV change over time.