Nir Ayalon

Adolescent BMI trajectory and risk of diabetes versus coronary disease.

BACKGROUND The association of body-mass index (BMI) from adolescence to adulthood with obesity-related diseases in young adults has not been completely delineated. METHODS We conducted a prospective study in which we followed 37,674 apparently healthy young men for incident angiography-proven coronary heart disease and diabetes through the Staff Periodic Examination Center of the Israeli Army Medical Corps. The height and weight of participants were measured at regular intervals, with the first measurements taken when they were 17 years of age. RESULTS During approximately 650,000 person-years of follow-up (mean follow-up, 17.4 years), we documented 1173 incident cases of type 2 diabetes and 327 of coronary heart disease. In multivariate models adjusted for age, family history, blood pressure, lifestyle factors, and biomarkers in blood, elevated adolescent BMI (the weight in kilograms divided by the square of the height in meters; mean range for the first through last deciles, 17.3 to 27.6) was a significant predictor of both diabetes (hazard ratio for the highest vs. the lowest decile, 2.76; 95% confidence interval [CI], 2.11 to 3.58) and angiography-proven coronary heart disease (hazard ratio, 5.43; 95% CI, 2.77 to 10.62). Further adjustment for BMI at adulthood completely ablated the association of adolescent BMI with diabetes (hazard ratio, 1.01; 95% CI, 0.75 to 1.37) but not the association with coronary heart disease (hazard ratio, 6.85; 95% CI, 3.30 to 14.21). After adjustment of the BMI values as continuous variables in multivariate models, only elevated BMI in adulthood was significantly associated with diabetes (β=1.115, P=0.003; P=0.89 for interaction). In contrast, elevated BMI in both adolescence (β=1.355, P=0.004) and adulthood (β=1.207, P=0.03) were independently associated with angiography-proven coronary heart disease (P=0.048 for interaction). CONCLUSIONS An elevated BMI in adolescence--one that is well within the range currently considered to be normal--constitutes a substantial risk factor for obesity-related disorders in midlife. Although the risk of diabetes is mainly associated with increased BMI close to the time of diagnosis, the risk of coronary heart disease is associated with an elevated BMI both in adolescence and in adulthood, supporting the hypothesis that the processes causing incident coronary heart disease, particularly atherosclerosis, are more gradual than those resulting in incident diabetes. (Funded by the Chaim Sheba Medical Center and the Israel Defense Forces Medical Corps.).

Progression of Normotensive Adolescents to Hypertensive Adults. A Study of 26 980 Teenagers

Although prehypertension at adolescence is accepted to indicate increased future risk of hypertension, large-scale/long follow-up studies are required to better understand how adolescent blood pressure (BP) tracks into young adulthood. We studied 23 191 male and 3789 female adolescents from the Metabolic Lifestyle and Nutrition Assessment in Young Adults cohort (mean age: 17.4 years) with BP <140/90 mm Hg at enrollment or categorized by current criteria for pediatric BP and body mass index (BMI) values. Participants were prospectively followed up with repeated BP measurements between ages 25 and 42 years and retrospectively between ages 17 and 25 years for the incidence of hypertension. We identified 3810 new cases of hypertension between ages 17 and 42 years. In survival analyses, the cumulative risk of hypertension between ages 17 and 42 years was 3 to 4 times higher in men than in women. Using Cox regression models adjusted for age, BMI, and stratified by baseline BP, the hazard ratio of hypertension increased gradually across BP groups within the normotensive range at age 17 years, without a discernible threshold effect, reaching a hazard ratio of 2.50 (95% CI: 1.75 to 3.57) for boys and 2.31 (95% CI: 0.71 to 7.60) for girls in the group with BP at 130 to 139/85 to 89 mm Hg. BMI at age 17 years was strongly associated with future risk of hypertension even when adjusted to BP at age 17 years, particularly in boys. Yet, BMI at age 30 years attenuated this association, more evidently in girls. In conclusion, BP at adolescence, even in the low-normotensive range, linearly predicts progression to hypertension in young adulthood. This progression and the apparent interaction between BP at age 17 years and BMI at adolescence and at adulthood are sex dependent.

Relationship of Plasma Galectin-3 to Renal Function in Patients With Heart Failure: Effects of Clinical Status, Pathophysiology of Heart Failure, and Presence or Absence of Heart Failure

Background Galectin-3 (GAL-3), a β-galactoside–binding protein, is a new clinical biomarker believed to reflect cardiac remodeling/fibrosis in patients with heart failure (HF). Plasma GAL-3 is inversely related to renal function. It is not known whether the relationship between renal function and GAL-3 is influenced by clinical decompensation, type of HF, or the presence or absence of clinical HF. Methods and Results Patients were prospectively categorized as having acute decompensated HF or stable HF on the basis of clinical status and as having HF with reduced left ventricular ejection fraction or HF with preserved left ventricular ejection fraction. Plasma GAL-3 was measured by enzyme-linked immunosorbent assay in patients with HF (n=75), control patients without HF (n=32), and control patients without HF with moderate renal insufficiency (n=12). Compared to controls without HF (14±4 ng/mL), GAL-3 was higher in patients with both acute decompensated HF (23±11 ng/mL) and stable HF (22±10 ng/mL) (P<0.001 versus controls for both) but did not differ between acute decompensated HF and stable HF (P=0.75). Likewise, GAL-3 was elevated in both HF with preserved left ventricular ejection fraction (23±9 ng/mL) and HF with reduced left ventricular ejection fraction (22±11 ng/mL) (P<0.001 versus controls for both) but did not differ between HF with preserved ejection fraction and HF with reduced ejection fraction (P=0.37). GAL-3 correlated strongly with estimated glomerular filtration rate, both in patients with HF (r=−0.75, P<0.001) and in patients without HF (r=−0.82, P<0.001), and this relationship was unaffected by the presence or absence of clinical HF. Conclusions Plasma GAL-3 is inversely related to renal function in patients with and without clinical HF. Concentrations of plasma GAL-3 do not seem to depend on the level of compensation or type of HF. Furthermore, the relationship between GAL-3 and renal function seems to be affected little or not at all by the presence or absence of clinical HF.

Lipoic acid prevention of neural tube defects in offspring of rats with streptozocin-induced diabetes

OBJECTIVE Increased oxidant stress has been suggested to play a role in the pathogenesis of disturbed embryogenesis in diabetic pregnancies. The present study was conducted to determine whether administration of lipoic acid, a naturally occurring antioxidant, would reduce the incidence of diabetic embryopathy in the streptozocin-induced diabetic rat model. STUDY DESIGN After conception, rats were randomly distributed to 5 groups. From day 1, rats were daily injected intraperitoneally with either lipoic acid, 30 mg/kg, or vehicle. At day 6, rats from groups 3, 4, and 5 were made diabetic by a single intraperitoneal injection of streptozocin. Group 4 rats were injected with lipoic acid from day 1 to day 6, after vehicle treatment until day 17. At day 17 of gestation, rats were killed. The fetuses were released from the yolk sacs and surrounding decidua and were examined for size, resorption rate, and neural tube defects. RESULTS Pregnant diabetic rats treated with vehicle lost weight during pregnancy (-3.2 +/- 1.9 g/d), as opposed to normal pregnancy-related weight gain (3.5 +/- 0.5 g/d). Treatment with lipoic acid protected against diabetes-induced weight loss, without a measurable effect on fed-state glucose concentrations. Daily treatment with lipoic acid (pregnancy days 1 to 17) was efficient in reducing the resorption rate from 24.0% +/- 9.5% in vehicle-treated diabetic rats to 10.2% +/- 4.8% in lipoic acid-treated diabetic rats (P <.05). The rate of neural tube defects in diabetic rats treated with lipoic acid throughout the pregnancy was reduced from 26.0% +/- 7.0% to 10.2% +/- 3.2% (P <.05). In rats treated only during pregnancy days 1 to 5 (before diabetes induction), lipoic acid failed to exert its protective effects against neural tube defects, which emphasizes the importance of the presence of lipoic acid during the organogenesis period. The atherosis of placental vasculature demonstrated in the vehicle-treated diabetic rats was absent from placentas obtained from lipoic acid-treated diabetic animals. CONCLUSIONS Our data demonstrate a protective effect of lipoic acid against diabetic embryopathy, fetal losses, and ultrastructural alteration of diabetic placentas.

Preclinical Systolic and Diastolic Dysfunctions in Metabolically Healthy and Unhealthy Obese Individuals

Background—Despite the substantial overlap of obesity and metabolic disease, there is heterogeneity with respect to cardiovascular risk. We sought to investigate preclinical differences in systolic and diastolic function in obesity, and specifically compare obese individuals with and without metabolic syndrome (MS). Methods and Results—Obese individuals without cardiac disease with (OB/MS+, n=124) and without (OB/MS−, n=37) MS were compared with nonobese controls (n=29). Diastolic function was assessed by transmitral and tissue Doppler. Global longitudinal strain (LS) and time-based dyssynchrony were assessed by speckle tracking. Both OB/MS− and OB/MS+ groups had similar ejection fraction but worse systolic mechanics as assessed by LS and dyssynchrony when compared with nonobese controls. Specifically, OB/MS− had 2.5% lower LS (SE, 0.7%; P=0.001 in multivariable-adjusted analyses) and 10.8 ms greater dyssynchrony (SE, 3.3 ms; P=0.002), and OB/MS+ had 1.0% lower LS (SE, 0.3%; P<0.001) and 7.8 ms greater dyssynchrony (SE, 1.5 ms; P<0.001) when compared with controls. Obesity was associated with impaired diastolic function regardless of MS status, as evidenced by greater left atrial diameter and left ventricular mass although diastolic dysfunction was more pronounced in OB/MS+ than in OB/MS− individuals. Conclusions—Obesity is associated with subclinical differences in both systolic and diastolic function regardless of the presence or absence of MS although MS seems to be associated with worse diastolic dysfunction. When compared with controls, metabolically healthy obese had lower LS, greater dyssynchrony, and early diastolic dysfunction, supporting the notion that obesity per se may have adverse cardiovascular effects regardless of metabolic disease.

Impaired Right Ventricular Hemodynamics Indicate Preclinical Pulmonary Hypertension in Patients With Metabolic Syndrome

Background Metabolic disease can lead to intrinsic pulmonary hypertension in experimental models. The contributions of metabolic syndrome (MetS) and obesity to pulmonary hypertension and right ventricular dysfunction in humans remain unclear. We investigated the association of MetS and obesity with right ventricular structure and function in patients without cardiovascular disease. Methods and Results A total of 156 patients with MetS (mean age 44 years, 71% women, mean body mass index 40 kg/m2), 45 similarly obese persons without MetS, and 45 nonobese controls underwent echocardiography, including pulsed wave Doppler measurement of pulmonary artery acceleration time (PAAT) and ejection time. Pulmonary artery systolic pressure was estimated from PAAT using validated equations. MetS was associated with lower tricuspid valve e′ (right ventricular diastolic function parameter), shorter PAAT, shorter ejection time, and larger pulmonary artery diameter compared with controls (P<0.05 for all). Estimated pulmonary artery systolic pressure based on PAAT was 42±12 mm Hg in participants with MetS compared with 32±9 and 32±10 mm Hg in obese and nonobese controls (P for ANOVA <0.0001). After adjustment for age, sex, hypertension, diabetes, body mass index, and triglycerides, MetS remained associated with a 20‐ms–shorter PAAT (β=−20.4, SE=6.5, P=0.002 versus obese). This association persisted after accounting for left ventricular structure and function and after exclusion of participants with obstructive sleep apnea. Conclusions MetS is associated with abnormal right ventricular and pulmonary artery hemodynamics, as shown by shorter PAAT and subclinical right ventricular diastolic dysfunction. Estimated pulmonary artery systolic pressures are higher in MetS and preclinical metabolic heart disease and raise the possibility that pulmonary hypertension contributes to the pathophysiology of metabolic heart disease.

Incomplete Revascularization in Patients Treated With Percutaneous Coronary Intervention: When Enough Is Enough

The optimal degree of revascularization for patients with multivessel coronary artery disease is not well established. Although there is growing evidence to support early and more complete revascularization of significant noninfarct artery stenoses among selected patients with ST-segment elevation

Mitochondrial encoded NADH dehydrogenase 5 (MT-ND5) gene point mutation presents as late onset cardiomyopathy

a Cardiovascular Section and Evans Department of Medicine, Boston University School of Medicine, Boston, MA, United States b Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA, United States c BUSM Center for Human Genetics, Boston University School of Medicine, Boston, MA, United States d Boston University Medical Campus Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, MA, United States

Preclinical Alterations in Myocardial Microstructure in People with Metabolic Syndrome

Metabolic syndrome (MetS) can lead to myocardial fibrosis, diastolic dysfunction, and eventual heart failure. This study evaluated alterations in myocardial microstructure in people with MetS by using a novel algorithm to characterize ultrasonic signal intensity variation.