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.

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.

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.

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.

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

 To determine the role of early onset versus late onset hypertension as a risk factor for hypertension in offspring and cardiovascular death. Multigenerational, prospective cohort study. Framingham Heart Study.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Genetic determinants of haemolysis in sickle cell anaemia.

Haemolytic anaemia is variable among patients with sickle cell anaemia and can be estimated by reticulocyte count, lactate dehydrogenase, aspartate aminotransferase and bilirubin levels. Using principal component analysis of these measurements we computed a haemolytic score that we used as a subphenotype in a genome-wide association study. We identified in one cohort and replicated in two additional cohorts the association of a single nucleotide polymorphism in NPRL3 (rs7203560; chr16p13·3) (P = 6·04 × 10(-07) ).

Circulating CD34(+) progenitor cell frequency is associated with clinical and genetic factors.

Circulating blood CD34(+) cells consist of hematopoietic stem/progenitor cells, angiogenic cells, and endothelial cells. In addition to their clinical use in hematopoietic stem cell transplantation, CD34(+) cells may also promote therapeutic neovascularization. Therefore, understanding the factors that influence circulating CD34(+) cell frequency has wide implications for vascular biology in addition to stem cell transplantation.

Distribution and clinical correlates of the interleukin receptor family member soluble ST2 in the Framingham Heart Study.

Background: Soluble ST2 (sST2) is a cardiac biomarker whose concentration rises in response to myocardial strain. Increased sST2 concentrations may predict adverse outcomes in patients with heart failure and myocardial infarction. Because sST2 was largely undetectable with first-generation assays in ambulatory individuals, there are few data regarding its distribution and correlates in community-based populations.

Clinical and genetic correlates of growth differentiation factor 15 in the community.

Background: Growth differentiation factor 15 (GDF15), a stress-responsive cytokine produced in cardiovascular cells under conditions of inflammation and oxidative stress, is emerging as an important prognostic marker in individuals with and without existing cardiovascular disease (CVD). We therefore examined the clinical and genetic correlates of circulating GDF15 concentrations, which have not been investigated collectively.

Methods: Plasma GDF15 concentrations were measured in 2991 participants in the Framingham Offspring Study who were free of clinically overt CVD (mean age, 59 years; 56% women).

Prognostic utility of novel biomarkers of cardiovascular stress: the Framingham Heart Study.

Background: Biomarkers for predicting cardiovascular events in community-based populations have not consistently added information to standard risk factors. A limitation of many previously studied biomarkers is their lack of cardiovascular specificity.

Methods And Results: To determine the prognostic value of 3 novel biomarkers induced by cardiovascular stress, we measured soluble ST2, growth differentiation factor-15, and high-sensitivity troponin I in 3428 participants (mean age, 59 years; 53% women) in the Framingham Heart Study.