An Early-Onset Subgroup of Type 2 Diabetes: A Multigenerational, Prospective Analysis in the Framingham Heart Study.

OBJECTIVE: To assess the relation of type 2 diabetes occurring earlier (age <55 years) versus later in life to the risk of cardiovascular death and to diabetes in offspring. RESEARCH DESIGN AND METHODS: In the Framingham Heart Study, a community-based prospective cohort study, glycemic status was ascertained at serial examinations over six decades among 5,571 first- and second-generation participants with mortality data and 2,123 second-generation participants who initially did not have diabetes with data on parental diabetes status. We assessed cause of death in a case (cardiovascular death)-control (noncardiovascular death) design and incident diabetes in offspring in relation to parental early-onset diabetes. RESULTS: Among the participants in two generations (N = 5,571), there were 1,822 cardiovascular deaths (including 961 coronary deaths). The odds of cardiovascular versus noncardiovascular death increased with decreasing age of diabetes onset (P < 0.001 trend). Compared with never developing diabetes, early-onset diabetes conferred a 1.81-fold odds (95% CI 1.10-2.97, P = 0.02) of cardiovascular death and 1.75-fold odds (0.96-3.21, P = 0.07) of coronary death, whereas later-onset diabetes was not associated with greater risk for either (P = 0.09 for cardiovascular death; P = 0.51 for coronary death). In second-generation participants, having a parent with early-onset diabetes increased diabetes risk by 3.24-fold (1.73-6.07), whereas having one or both parents with late-onset diabetes increased diabetes risk by 2.19-fold (1.50-3.19). CONCLUSIONS: Our findings provide evidence for a diabetes subgroup with an early onset, a stronger association with cardiovascular death, and higher transgenerational transmission.

Self-reported Age of Hypertension Onset and Hypertension-Mediated Organ Damage in Middle-Aged Individuals.

BACKGROUND: Objectively defined early onset hypertension, based on repeated blood pressure measurements, is a strong risk factor for cardiovascular disease (CVD). We aimed to assess if also self-reported hypertension onset age is associated with hypertension-mediated organ damage (HMOD). Additionally, we evaluated the agreement between self-reported and objectively defined hypertension onset age. METHODS: We studied 2,649 participants (50 ± 4 years at the time of outcome assessment, 57% women) of the Coronary Artery Risk Development in Young Adults (CARDIA) study who underwent measurements for echocardiographic left ventricular hypertrophy (LVH), left ventricular diastolic dysfunction (LVDD), coronary calcification, and albuminuria. We divided the participants into groups according to self-reported hypertension onset age (<35 years, 35-44 years, ≥45 years, and no hypertension). We used multivariable-adjusted logistic regression models to assess the relation between self-reported hypertension onset age with the presence of HMOD, with those who did not report hypertension as the referent group. RESULTS: Compared with individuals without self-reported hypertension, self-reported hypertension onset at <35 years was associated with LVH (odds ratio (OR), 2.38; 95% confidence interval (CI), 1.51-3.76), LVDD (OR, 2.32; 95% CI, 1.28-4.18, coronary calcification (OR, 2.87; 95% CI, 1.50-5.47), and albuminuria (OR, 1.62; 95% CI, 0.81-3.26). Self-reported hypertension onset at ≥45 years was only associated with LVDD (OR, 1.81; 95% CI, 1.06-3.08). The agreement between self-reported and objectively defined hypertension onset age groups was 78-79%. CONCLUSIONS: Our findings suggest that self-reported hypertension onset age, a pragmatically feasible assessment in clinical practice, is a reasonable method for assessing risk of HMOD and CVD.

Early Onset Hypertension Is Associated With Hypertensive End-Organ Damage Already by MidLife.

Early onset hypertension confers increased risk for cardiovascular mortality in the community. Whether early onset hypertension also promotes the development of target end-organ damage (TOD), even by midlife, has remained unknown. We studied 2680 middle-aged CARDIA study (Coronary Artery Risk Development in Young Adults) Study participants (mean age 50±4 years, 57% women) who underwent up to 8 serial blood pressure measurements between 1985 and 2011 (age range at baseline 18-30 years) in addition to assessments of echocardiographic left ventricular hypertrophy, coronary calcification, albuminuria, and diastolic dysfunction in 2010 to 2011. Age of hypertension onset was defined as the age at first of 2 consecutively attended examinations with blood pressure ≥140/90 mm Hg or use of antihypertensive medication. Participants were divided in groups by hypertension onset age (<35 years, 35-44 years, ≥45 years, or no hypertension). While adjusting for TOD risk factors, including systolic blood pressure, we used logistic regression to calculate odds ratios for cases (participants with TOD) versus controls (participants without TOD) to examine the relation of hypertension onset age and hypertensive TOD. Compared with normotensive individuals, hypertension onset at age <35 years was related to odds ratios of 2.29 (95% CI, 1.36-3.86), 2.94 (95% CI, 1.57-5.49), 1.12 (95% CI, 0.55-2.29), and 2.06 (95% CI, 1.04-4.05) for left ventricular hypertrophy, coronary calcification, albuminuria, and diastolic dysfunction, respectively. In contrast, hypertension onset at age ≥45 years was not related to increased odds of TOD. Our findings emphasize the importance of assessing age of hypertension onset in hypertensive patients to identify high-risk individuals for preventing hypertensive complications.

Implementation of a Multifaceted Interactive Electrodiagnostic Medicine Workshop in a Physical Medicine and Rehabilitation Residency Program.

Electrodiagnostic medicine is a required component of Physical Medicine and Rehabilitation residency education, but limited resources exist to guide curriculum development. Our objective was to create a focused workshop to enhance our residency program's electrodiagnostic curriculum. We created two separate 1.5-day workshops, one basic and one advanced, for all residents. Each workshop included didactic sessions, case discussion, question and answer sessions, demonstrations, and hands-on participation with direct supervision and feedback. Presurveys and postsurveys were administered to evaluate the value of the workshops. We also assessed trends in electrodiagnostic self-assessment examination scores. Residents reported clinical electrodiagnostic rotations to be more valuable to their education than previous didactic sessions and independent learning. Self-reported knowledge of electrodiagnostic concepts, resident comfort level in planning, performing, and interpreting studies, and perceived value in independent learning of electrodiagnostic medicine improved after implementation of the workshops. There was a 7% improvement in the American Association of Neuromuscular and Electrodiagnostic Medicine electrodiagnostic self-assessment examination score compared with the previous year and a 15% improvement in the Physical Medicine and Rehabilitation self-assessment examination electrodiagnostic subscore compared with the previous 5 yrs. All participants recommended similar educational experience for other residents. This successful workshop may serve as a resource for other training programs.

Cardiometabolic Traits and Systolic Mechanics in the Community.

BACKGROUND: Obesity and cardiometabolic dysfunction are associated with increased risk of heart failure and other cardiovascular diseases. We sought to examine the association of cardiometabolic traits with left ventricular (LV) cardiac mechanics. We hypothesized that specific obesity-related phenotypes are associated with distinct aspects of LV strain. METHODS AND RESULTS: We evaluated the associations of obesity-related phenotypes, including central adiposity, diabetes mellitus, insulin resistance, and circulating adipokine concentrations with echocardiographic measures of LV mechanical function among participants of the Framingham Heart Study Offspring and Third Generation cohorts. Among 6231 participants, the mean age was 51±16 years, and 54% were women. Greater body mass index was associated with worse LV longitudinal strain, radial strain (apical view), and longitudinal synchrony (multivariable-adjusted P<0.0001). After accounting for body mass index, we found that central adiposity, as measured by waist circumference, was associated with worse global longitudinal strain and synchrony (P≤0.006). Measures of insulin resistance, dyslipidemia, and diabetes mellitus also were associated with distinct aspects of LV mechanical function. Circulating leptin concentrations were associated with global longitudinal and radial strain (apical view, P<0.0001), whereas no such association was found with leptin receptor, adiponectin, or C-reactive protein. CONCLUSIONS: Our findings highlight the association of central obesity and related cardiometabolic phenotypes above and beyond body mass index with subclinical measures of LV mechanical function. Interestingly, obesity-related traits were associated with distinct aspects of LV mechanics, underscoring potential differential effects along specific LV planes of deformation. These findings may shed light onto obesity-related cardiac remodeling and heart failure.

Heritability and risks associated with early onset hypertension: multigenerational, prospective analysis in the Framingham Heart Study.

Objective To determine the role of early onset versus late onset hypertension as a risk factor for hypertension in offspring and cardiovascular death.Design Multigenerational, prospective cohort study.Setting Framingham Heart Study.Participants Two generations of community dwelling participants with blood pressure measurements performed at serial examinations spanning six decades: 3614 first generation participants with mortality data and 1635 initially non-hypertensive second generation participants with data available on parental blood pressure.Main outcome measures The main outcome measures were relation of parental early onset hypertension (age <55 years) with incidence of hypertension in offspring, using regression analyses, and relation of age at hypertension onset with cause specific mortality using a case (cardiovascular death) versus control (non-cardiovascular death) design.Results In second generation participants, having one or both parents with late onset hypertension did not increase the risk of hypertension compared with having parents with no hypertension; by contrast, the hazard ratios of hypertension were 2.0 (95% confidence interval 1.2 to 3.5) and 3.5 (1.9 to 6.1) in participants with one and both parents with early onset hypertension, respectively. In first generation decedents, 1151 cardiovascular deaths occurred (including 630 coronary deaths). The odds of cardiovascular death increased linearly with decreasing age of hypertension onset (P<0.001 for trend). Compared with non-hypertensive participants, hypertension onset at age <45 years conferred an odds ratios of 2.2 (1.8 to 2.7) for cardiovascular death and 2.3 (1.8 to 2.9) for coronary death, whereas hypertension onset at age ≥65 years conferred a lower magnitude odds ratios of 1.5 (1.2 to 1.9) for cardiovascular death and 1.4 (0.98 to 1.9) for coronary death (P≤0.002 for differences in odds ratios between hypertension onset at age <45 and age ≥65).Conclusions Early onset and not late onset hypertension in parents was strongly associated with hypertension in offspring. In turn, early onset compared with late onset hypertension was associated with greater odds of cardiovascular, and particularly coronary, death. These findings suggest it may be important to distinguish between early onset and late onset hypertension as a familial trait when assessing an individual's risk for hypertension, and as a specific type of blood pressure trait when estimating risk for cardiovascular outcomes in adults with established hypertension.

Risk for hypertension crosses generations in the community: a multi-generational cohort study.

AIMS: Parental hypertension is known to predict high blood pressure (BP) in children. However, the extent to which risk for hypertension is conferred across multiple generations, notwithstanding the impact of environmental factors, is unclear. Our objective was therefore to evaluate the degree to which risk for hypertension extends across multiple generations of individuals in the community. METHODS AND RESULTS: We studied three generations of Framingham Heart Study participants with standardized blood pressure measurements performed at serial examinations spanning 5 decades (1948 through 2005): First Generation (n = 1809), Second Generation (n = 2631), and Third Generation (n = 3608, mean age 39 years, 53% women). To capture a more precise estimate of conferrable risk, we defined early-onset hypertension (age <55 years) as the primary exposure. In multinomial logistic regression models adjusting for standard risk factors as well as physical activity and daily intake of dietary sodium, risk for hypertension in the Third Generation was conferred simultaneously by presence of early-onset hypertension in parents [OR 2.10 (95% CI, 1.66-2.67), P < 0.001] as well as in grandparents [OR 1.33 (95% CI, 1.12-1.58), P < 0.01]. CONCLUSION: Early-onset hypertension in grandparents raises the risk for hypertension in grandchildren, even after adjusting for early-onset hypertension in parents and lifestyle factors. These results suggest that a substantial familial predisposition for hypertension exists, and this predisposition is not identical when assessed from one generation to the next. Additional studies are needed to elucidate the mechanisms underlying transgenerational risk for hypertension and its clinical implications.

Relations Between Aortic Stiffness and Left Ventricular Mechanical Function in the Community.

BACKGROUND: Aortic stiffness impairs optimal ventricular-vascular coupling and left ventricular systolic function, particularly in the long axis. Left ventricular global longitudinal strain (GLS) has recently emerged as a sensitive measure of early cardiac dysfunction. In this study, we investigated the relation between aortic stiffness and GLS in a large community-based sample. METHODS AND RESULTS: In 2495 participants (age 39-90 years, 57% women) of the Framingham Offspring and Omni cohorts, free of cardiovascular disease, we performed tonometry to measure arterial hemodynamics and echocardiography to assess cardiac function. Aortic stiffness was evaluated as carotid-femoral pulse wave velocity and as characteristic impedance, and GLS was calculated using speckle tracking-based measurements. In multivariable analyses adjusting for age, sex, height, systolic blood pressure, augmentation index, left ventricular structure, and additional cardiovascular risk factors, increased carotid-femoral pulse wave velocity (B±SE: 0.122±0.030% strain per SD, P<0.0001) and characteristic impedance (0.090±0.029, P=0.002) were both associated with worse GLS. We observed effect modification by sex on the relation between characteristic impedance and GLS (P=0.004); in sex-stratified multivariable analyses, the relation between greater characteristic impedance and worse GLS persisted in women (0.145±0.039, P=0.0003) but not in men (P=0.73). CONCLUSIONS: Multiple measures of increased aortic stiffness were cross-sectionally associated with worse GLS after adjusting for hemodynamic variables. Parallel reductions in left ventricular long axis shortening and proximal aortic longitudinal strain in individuals with a stiffened proximal aorta, from direct mechanical ventricular-vascular coupling, offers an alternative explanation for the observed relations.

Hemodynamic Correlates of Blood Pressure in Older Adults: The Atherosclerosis Risk in Communities (ARIC) Study.

The primary aim of the present study was to identify the hemodynamic correlates of both steady and pulsatile blood pressure (BP) in community-dwelling older adults. In 3762 adults aged 70 to 89 years, significant hemodynamic determinants of both brachial and carotid systolic BP included arterial stiffness as measured by aortic pulse wave velocity, stroke volume (via echocardiography), arterial wave reflection, left ventricular ejection time, and upstroke time. The strongest influence was exerted by arterial stiffness. The steady-state component of blood pressure, mean arterial pressure, was associated with both cardiac index and total peripheral resistance (TPR), but was more strongly associated with TPR. Results were similar when participants taking antihypertensive medications were excluded from analyses. The overall findings suggest that mean arterial pressure is associated strongly with TPR and that significant hemodynamic correlates of systolic BP included arterial stiffness, stroke volume, and arterial wave reflection.

Association of an Index of Healthy Aging With Incident Cardiovascular Disease and Mortality in a Community-Based Sample of Older Adults.

BACKGROUND: The healthy aging index (HAI) was developed as a marker of health in multiple systems that can identify individuals who age most successfully. METHODS: We calculated an HAI in 934 Framingham Offspring Study participants aged 60 or older at baseline. Heart rate and C-reactive protein (CRP) were added in modified versions of the HAI. Cox proportional hazard models were used to quantify the association of the HAI with mortality, cardiovascular disease (CVD), and cancer. We used fully conditional specification to multiply impute missing values for HAI components, increasing the sample size by 44%. RESULTS: Over 10 years of follow-up, there were 138 deaths, 103 incident cases of CVD, and 138 incident cases of cancer. In models adjusted for age, sex, and behavioral risk factors, the HAI was associated with mortality (hazard ratio [HR] per unit of HAI 1.24, 95% confidence interval [CI] 1.13-1.36) and with CVD (HR 1.27, 95% CI 1.13-1.42), but not with cancer (HR 1.01, 95% CI 0.91-1.11) in observed (non-missing) data. In multivariable models further adjusting for prevalent diseases, results were slightly attenuated. When including heart rate and CRP, a modified HAI gave stronger associations. Results with imputed data are similar to results from complete case analyses. CONCLUSIONS: In our large community-based sample, the HAI is a strong predictor of mortality and CVD. Other factors that are strongly associated with mortality, such as heart rate and CRP can improve the ability of the HAI to identify the healthiest older adults.

Distinct Aspects of Left Ventricular Mechanical Function Are Differentially Associated With Cardiovascular Outcomes and All-Cause Mortality in the Community.

BACKGROUND: There are few data relating novel measures of left ventricular (LV) mechanical function to cardiovascular disease (CVD) outcomes in the community. Whether distinct components of LV mechanical function provide information regarding risk for different CVD outcomes is unclear. METHODS AND RESULTS: We used speckle tracking echocardiography to quantify distinct components of LV mechanical function (measured as LV strain in multiple planes) in 2831 Framingham Offspring Study participants (mean age, 66 years; 57% women, 97% with LV fractional shortening >0.29). Participants were followed for 6.0±1.2 years for onset of 69 coronary heart disease (CHD), 71 heart failure (HF), and 199 mortality events. Adjusting for CVD risk factors, longitudinal LV strain appeared associated with incident CHD (hazards ratio [HR] per SD increment, 1.29; 95% confidence interval [CI], 1.00-1.67; P=0.05), whereas circumferential and radial strain were not (P>0.37 for both); however, the association of longitudinal strain with CHD was nonsignificant after Bonferroni correction. By contrast, circumferential strain was a significant predictor of incident HF (HR per SD increment, 1.79; 95% CI, 1.35-2.37; P<0.0001). Decrements in circumferential, radial, and longitudinal strain measures were related to all-cause mortality (P<0.008 for all). Results remained similar in multivariable models adjusting additionally for the conventional echocardiographic measures of LV mass and fractional shortening. CONCLUSIONS: In our large, community-based sample, distinct components of LV mechanical function were associated with specific CVD outcomes. Additional studies are needed to replicate these findings and investigate the prognostic and therapeutic utility of these novel measures of LV mechanical function.

Distinct metabolomic signatures are associated with longevity in humans.

Alterations in metabolism influence lifespan in experimental models, but data in humans are lacking. Here we use liquid chromatography/mass spectrometry to quantify 217 plasma metabolites and examine their relation to longevity in a large cohort of men and women followed for up to 20 years. We find that, higher concentrations of the citric acid cycle intermediate, isocitrate, and the bile acid, taurocholate, are associated with lower odds of longevity, defined as attaining 80 years of age. Higher concentrations of isocitrate, but not taurocholate, are also associated with worse cardiovascular health at baseline, as well as risk of future cardiovascular disease and death. None of the metabolites identified are associated with cancer risk. Our findings suggest that some, but not all, metabolic pathways related to human longevity are linked to the risk of common causes of death.

Left ventricular mechanical function: clinical correlates, heritability, and association with parental heart failure.

AIMS: Non-invasive measures of cardiac mechanical function may have the potential to serve as markers of risk for heart failure; however, limited data exist regarding clinical correlates and heritability of these measures in the community. METHODS AND RESULTS: We used speckle-tracking echocardiography to assess LV strain and synchrony in the Framingham Offspring Study (n = 2816; mean age 67 years, 54% women). In multivariable regression analyses, male gender (vs. female, P < 0.001), higher heart rate (P < 0.0001), and presence of cardiovascular disease (P < 0.001) were associated with worse global peak strains across all planes analysed (longitudinal, transverse, circumferential, and radial). Higher diastolic blood pressure and diabetes were associated with worse longitudinal strain (P < 0.01), and greater body mass index was associated with worse radial strain (P = 0.0004). Overall, however, clinical correlates accounted for only 4-19% of the variation in measures of LV mechanical function. Select measures of LV strain were heritable: longitudinal strain (h(2) = 16%, P = 0.002), transverse strain (h(2) = 15%, P = 0.006), and circumferential strain (h(2) = 30%, P < 0.0001). Furthermore, in a subset of 1437 participants with parental data available, parental heart failure was associated with worse circumferential strain in the offspring free of heart failure (P = 0.01). CONCLUSIONS: Our investigation in a large community-based sample identified heritablity and clinical correlates of LV mechanical function, and highlighted an association of parental heart failure with worse global circumferential strain in offspring.

Relation between soluble ST2, growth differentiation factor-15, and high-sensitivity troponin I and incident atrial fibrillation.

BACKGROUND: We investigated whether circulating concentrations of soluble ST2, growth differentiation factor-15 (GDF-15), and high-sensitivity troponin I (hsTnI) are associated with incident atrial fibrillation (AF) and whether these biomarkers improve current risk prediction models including AF risk factors, B-type natriuretic peptide (BNP), and C-reactive protein (CRP). METHODS: We studied the relation between soluble ST2, GDF-15, and hsTnI and development of AF in Framingham Heart Study participants without prevalent AF. We used Cox proportional hazard regression analysis to examine the relation of incident AF during a 10-year follow-up period with each biomarker. We adjusted for standard AF clinical risk factors, BNP, and CRP. RESULTS: The mean age of the 3,217 participants was 59 ± 10 years, and 54% were women. During a 10-year follow-up, 242 participants developed AF. In age- and sex-adjusted models, GDF-15 and hsTnI were associated with risk of incident AF; however, after including the AF risk factors and BNP and CRP, only hsTnI was significantly associated with AF (hazard ratio per 1 SD of loge hsTnI, 1.12, 95% CI 1.00-1.26, P = .045). The c statistic of the base model including AF risk factors, BNP, and CRP was 0.803 (95% CI 0.777-0.830) and did not improve by adding individual or all 3 biomarkers. None of the discrimination and reclassification statistics were significant compared with the base model. CONCLUSION: In a community-based cohort, circulating hsTnI concentrations were associated with incident AF. None of the novel biomarkers evaluated improved AF risk discrimination or reclassification beyond standard clinical AF risk factors and biomarkers.

Common genetic variation at the IL1RL1 locus regulates IL-33/ST2 signaling.

The suppression of tumorigenicity 2/IL-33 (ST2/IL-33) pathway has been implicated in several immune and inflammatory diseases. ST2 is produced as 2 isoforms. The membrane-bound isoform (ST2L) induces an immune response when bound to its ligand, IL-33. The other isoform is a soluble protein (sST2) that is thought to be a decoy receptor for IL-33 signaling. Elevated sST2 levels in serum are associated with an increased risk for cardiovascular disease. We investigated the determinants of sST2 plasma concentrations in 2,991 Framingham Offspring Cohort participants. While clinical and environmental factors explained some variation in sST2 levels, much of the variation in sST2 production was driven by genetic factors. In a genome-wide association study (GWAS), multiple SNPs within IL1RL1 (the gene encoding ST2) demonstrated associations with sST2 concentrations. Five missense variants of IL1RL1 correlated with higher sST2 levels in the GWAS and mapped to the intracellular domain of ST2, which is absent in sST2. In a cell culture model, IL1RL1 missense variants increased sST2 expression by inducing IL-33 expression and enhancing IL-33 responsiveness (via ST2L). Our data suggest that genetic variation in IL1RL1 can result in increased levels of sST2 and alter immune and inflammatory signaling through the ST2/IL-33 pathway.

Age- and sex-based reference limits and clinical correlates of myocardial strain and synchrony: the Framingham Heart Study.

BACKGROUND: There is rapidly growing interest in applying measures of myocardial strain and synchrony in clinical investigations and in practice; data are limited regarding their reference ranges in healthy individuals. METHODS AND RESULTS: We performed speckle-tracking-based echocardiographic measures of left ventricular myocardial strain and synchrony in healthy adults (n=739, mean age 63 years, 64% women) without cardiovascular disease. Reference values were estimated using quantile regression. Age- and sex-based upper (97.5th quantile) limits were: -14.4% to -17.1% (women) and -14.4 to -15.2% (men) for longitudinal strain; -22.3% to -24.7% (women) and -17.9% to -23.7% (men) for circumferential strain; 121 to 165 ms (women) and 143 to 230 ms (men) for longitudinal segmental synchrony (SD of regional time-to-peak strains); and 200 to 222 ms (women) and 216 to 303 ms (men) for transverse segmental synchrony. In multivariable analyses, women had ≈1.7% greater longitudinal strain, ≈2.2% greater transverse strain, and ≈3.2% greater circumferential strain (P<0.0001 for all) compared with men. Older age and higher diastolic blood pressure, even within the normal range, were associated with worse transverse segmental synchrony (P<0.001). Overall, covariates contributed to ≤12% of the variation in myocardial strain or synchrony in this healthy sample. CONCLUSIONS: We estimated age- and sex-specific reference limits for measures of left ventricular strain and synchrony in a healthy community-based sample, wherein clinical covariates contributed to only a modest proportion of the variation. These data may facilitate the interpretation of left ventricular strain-based measures obtained in future clinical research and practice.

Reproducibility of speckle-tracking-based strain measures of left ventricular function in a community-based study.

BACKGROUND: The reproducibility of echocardiographic measurements of myocardial strain, performed in a community-based setting, has not been reported previously. METHODS: The reproducibility of left ventricular strain measurements was examined in two samples of 20 participants each from the Offspring Cohort of the Framingham Heart Study (mean age, 63 ± 9 years; 59% women). Two-dimensional speckle-tracking-based measurements of global peak left ventricular strain in systole were performed in the apical four-chamber, apical two-chamber, and midventricular parasternal short-axis views. RESULTS: Interobserver intraclass correlation coefficients were ≥0.84 for all global strain measurements, with average coefficients of variation of ≤4% for global longitudinal and circumferential strain and <8% for global transverse and radial strain. For left ventricular strain measurements performed in each of the three views, intraobserver intraclass correlation coefficients were ≥0.91 among time points spanning a total 8-month period. The average coefficients of variation were <6% for global longitudinal and circumferential strain and <9% for global transverse and radial strain. Interobserver and intraobserver reproducibility findings were similar in analyses adjusting for frame rate. CONCLUSIONS: Excellent reproducibility of global longitudinal and circumferential strain measurements and very good reproducibility of global transverse and radial strain measurements were observed. Taken together, these findings demonstrate the reproducibility of performing echocardiographic strain measurements in a large, epidemiologic community-based setting.