The relation of digital vascular function to cardiovascular risk factors in African-Americans using digital tonometry: the Jackson Heart Study.

Digital vascular tone and function, as measured by peripheral arterial tonometry (PAT), are associated with cardiovascular risk and events in non-Hispanic whites. There are limited data on relations between PAT and cardiovascular risk in African-Americans. PAT was performed on a subset of Jackson Heart Study participants using a fingertip tonometry device. Resting digital vascular tone was assessed as baseline pulse amplitude. Hyperemic vascular response to 5 minutes of ischemia was expressed as the PAT ratio (hyperemic/baseline amplitude ratio). Peripheral augmentation index (AI), a measure of relative wave reflection, also was estimated. The association of baseline pulse amplitude (PA), PAT ratio, and AI to risk factors was assessed using stepwise multivariable models. The study sample consisted of 837 participants from the Jackson Heart Study (mean age, 54 ± 11 years; 61% women). In stepwise multivariable regression models, baseline pulse amplitude was related to male sex, body mass index, and diastolic blood pressure (BP), accounting for 16% of the total variability of the baseline pulse amplitude. Age, male sex, systolic BP, diastolic BP, antihypertensive medication, and prevalent cardiovascular disease contributed to 11% of the total variability of the PAT ratio. Risk factors (primarily age, sex, and heart rate) explained 47% of the total variability of the AI. We confirmed in our cohort of African-Americans, a significant relation between digital vascular tone and function measured by PAT and multiple traditional cardiovascular risk factors. Further studies are warranted to investigate the utility of these measurements in predicting clinical outcomes in African-Americans.

Diabetes status modifies the association between carotid intima-media thickness and incident heart failure: The Atherosclerosis Risk in Communities study.

AIMS: Increasing carotid intima-media thickness (CIMT) is associated with incident heart failure (HF). We investigated whether this association differs by diabetes status. METHODS: We characterized 13,590 Atherosclerosis Risk in Communities Study participants free of baseline HF into normal fasting glucose (NFG, glucose <100mg/dl), impaired fasting glucose (IFG, glucose 100-125mg/dl), and type 2 diabetes (T2D, glucose ≥126mg/dl, self-report, or use of diabetes drugs). CIMT was assessed by B-mode ultrasound. Incident HF was defined using ICD-9 or 10 codes from hospitalizations and death certificates. Cox regression was used to estimate hazard ratios (HR) for incident HF, adjusting for age, sex, race, education, hypertension medication, blood pressure, BMI, waist circumference, HDL, LDL, triglycerides, lipid-lowering medication, smoking, alcohol, serum creatinine, and interim CHD. RESULTS: T2D participants had higher mean CIMT (0.79±0.20mm), compared to IFG (0.75±0.19mm) and NFG (0.70±0.17mm) (p<0.0001). Over 20.6years of median follow-up, 15% developed HF. Rates of HF (per 1000 person-years) were substantially higher for those with T2D (24.7), compared to IFG (7.7) and NFG (5.8). In adjusted analyses, the CIMT-HF association was significantly modified by diabetes status (Pinteraction=0.015): for NFG (HR per SD increase in CIMT: 1.27; 95%CI: 1.20-1.34), IFG (HR 1.18; 95%CI: 1.11-1.25) and T2D (HR 1.12; 95%CI: 1.05-1.21). CONCLUSIONS: CIMT is associated with increased risk of HF, particularly among persons without diabetes. Due to a high absolute risk of HF among adults with T2D, CIMT may be a less reliable predictor.

"2 for 1 Phenomenon" on Implantable Cardioverter Defibrillator Intracardiac Tracing.

"2 for 1 phenomenon" is simultaneous anterograde conduction over the fast and slow pathways of the atrioventricular (AV) nodal pathway, leading to a double ventricular response from each atrial beat. This phenomenon can initiate AV nodal reentrant tachycardia (AVNRT). The unique induction of AVNRT was observed in a patient with an implantable cardioverter defibrillator in our case. Minimal to no retrograde invasion of the slow pathway from the anterogradely conducted fast pathway depolarization is the most accepted explanation.

Synthesis and Investigation of Novel Spiro-isoxazolines as Anti-Cancer Agents.

A series of structurally diverse 4-bromo spiro-isoxazolines possessing a variety of aromatic and aliphatic substituents at the 3 position, were synthesized through a 1,3-dipolar cycloaddition followed by intramolecular cyclization of a pendant hydroxyl or carboxylic acid group. The biochemical antiproliferative activity was evaluated in vitro by using two breast cancer cell lines (MCF-7 and MDA-MB-231) and two prostate cancer cell lines (PC-3 and DU-145) using the MTT viability assay, and the IC50 values were obtained. Spiro-isoxazoline derivatives bearing a p-chloro or an o-dichloro aromatic substituent at the 3-position of the isoxazoline showed considerable antitumor activities in all four cell lines with IC50 value ranging from 43µM to 56µM.

Clinical correlates and prognostic significance of change in standardized left ventricular mass in a community-based cohort of African Americans.

BACKGROUND: Though left ventricular mass (LVM) predicts cardiovascular events (CVD) and mortality in African Americans, limited data exists on factors contributing to change in LVM and its prognostic significance. We hypothesized that baseline blood pressure (BP) and body mass index (BMI) and change in these variables over time are associated with longitudinal increases in LVM and that such increase is associated with greater incidence of CVD. METHODS AND RESULTS: We investigated the clinical correlates of change in standardized logarithmically transformed-LVM indexed to height2.7 (log-LVMI) and its association with incident CVD in 606 African Americans (mean age 58±6 years, 66% women) who attended serial examinations 8 years apart. Log-LVMI and clinical covariates were standardized within sex to obtain z scores for both visits. Standardized log-LVMI was modeled using linear regression (correlates of change in standardized log-LVMI) and Cox proportional hazards regression (incidence of CVD [defined as coronary heart disease, stroke, heart failure and intermittent claudication]). Baseline clinical correlates (standardized log-LVM, BMI, systolic BP) and change in systolic BP over time were significantly associated with 8-year change in standardized log-LVMI. In prospective analysis, change in standardized LVM was significantly (P=0.0011) associated with incident CVD (hazards ratio per unit standard deviation change log-LVMI 1.51, 95% CI 1.18 to 1.93). CONCLUSIONS: In our community-based sample of African Americans, baseline BMI and BP, and change in BP on follow-up were key determinants of increase in standardized log-LVMI, which in turn carried an adverse prognosis, underscoring the need for greater control of BP and weight in this group.

Oxonium Ion Mediated Synthesis of 4-Substituted Spiro-Isoxazolines.

The stereoselective synthesis of 4-bromo-spiro-isoxazolines was achieved in one step through the bromination of various isoxazoles that contain a pendant alcohol or carboxylic acid functional group. Isoxazole bromination leads to a bromonium ion intermediate which opens either by neighboring oxygen lone pair electrons or by intramolecular nucleophilic attack. Single X-ray crystal data provides evidence that the two contiguous stereocenters of the spiro-isoxazoline are formed by the anti intramolecular attack of the nucleophile relative to bromine since there is an anti stereochemical relationship between the spirocyclic ring oxygen and the bromine atom.