Prognostic impact of prolonged ventricular repolarization in hypertension

BACKGROUND: QT interval prolongation on the surface electrocardiogram (ECG) predicts cardiovascular complications in high-risk subjects, but its prognostic role in uncomplicated hypertension has been understudied. METHODS: For up to 13 years (average, 5.3 years), we followed up 2110 white patients with initially untreated essential hypertension (mean +/- SD age, 49 +/- 12 years; 55% men) without prevalent cardiovascular or renal disease who underwent 12-lead ECG before therapy. We excluded patients with ECG abnormalities including ischemia, necrosis, complete bundle branch block, atrial fibrillation, arrhythmias, and ventricular preexcitation. RESULTS: Heart rate-corrected QT interval (QTc) showed a weak but significant direct association with systolic blood pressure (r = 0.07; P<.001), diastolic blood pressure (r = 0.11; P<.001), and Cornell voltage (r = 0.06; P = .006). During follow-up, 84 patients developed new-onset ischemic heart disease (0.75 event per 100 patient-years). After adjustment (Cox model) for the effects of age, sex, diabetes mellitus, serum cholesterol level, serum creatinine level, smoking, left ventricular hypertrophy, and 24-hour systolic blood pressure, patients with a prolonged QTc (>or=450 milliseconds in women and >or=440 milliseconds in men) had a nearly 2-fold increase in risks of coronary events (hazard ratio, 1.95; 95% confidence interval, 1.12-3.42; P = .02) and cardiovascular death (hazard ratio, 2.05; 95% confidence interval, 1.03-4.37; P = .04). Coronary heart disease risk was independently higher by 33% (95% confidence interval, +7% to +66%; P = .01) for each 32-millisecond increase in QTc. CONCLUSIONS: Prolonged ventricular repolarization is a risk factor for ischemic heart disease and cardiovascular mortality in subjects with uncomplicated hypertension. Its prognostic significance adds to that of several traditional cardiovascular risk factors, including left ventricular hypertrophy.     

Medicinal and ethnoveterinary remedies of hunters in Trinidad

Background  

Ethnomedicines are used by hunters for themselves and their hunting dogs in Trinidad. Plants are used for snakebites, scorpion stings, for injuries and mange of dogs and to facilitate hunting success.     

Preclinical vascular damage in white postmenopausal women: the relevance of osteoprotegerin

Osteoprotegerin (OPG) has recently been implicated in human atherogenesis. Abdominal obesity represents an established risk factor for the onset and development of atherosclerotic damage. The aim of the present study was to investigate the link between OPG and abdominal fat and the relationship to precocious features of atherosclerotic disease such as brachial flow-mediated vasodilation (FMV) and the intima-media thickening (IMT) in 195 white postmenopausal women (age range, 43-75 years). The study population was divided into 2 groups: group 1-waist circumference <80 cm and group 2-waist circumference > or = 80 cm. Group 2 had higher menopausal years, body mass index, low-density lipoprotein cholesterol, triglycerides, C-reactive protein, and carotid IMT. High-density lipoprotein cholesterol was higher in group 1. Afterward, these groups were divided on the basis of a cutoff value of OPG (6.85 pmol/L) that was the median of its distribution: patients with OPG < or = 6.85 pmol/L were OPG(-), and those with OPG >6.85 pmol/L were OPG(+). The OPG(+) subjects in both had lower brachial FMV and higher carotid IMT in comparison with OPG(-) subjects. At the multivariate regression analysis, waist circumference, high-density lipoprotein cholesterol, C-reactive protein, and OPG were predictors of carotid mean IMT (beta = 0.55, P = .001; beta = -0.14, P = .001; beta = 0.16, P = .001; and beta = 0.14, P = .05, respectively) and age, OPG, low-density lipoprotein cholesterol, and brachial diameter of brachial FMV (beta = -0.13, P = .05; beta = -0.25, P = .001; beta = -0.14, P = .024; and beta = 0.48, P = .001, respectively). The conclusions are as follows: first, OPG levels did not appear to be conditioned by a risk factor such as abdominal obesity; and second, OPG levels are mainly linked to the evidence of vascular damage. On this basis, we could speculate that OPG levels may be considered not a cardiovascular risk condition but a defense against atherosclerotic progression.     

Combined chemo-radiotherapy for locally advanced non-small cell lung cancer: current status and future development

Currently, combinations of chemotherapy and radiotherapy are the standard treatment approach for locally advanced NSCLC patients. Concomitant chemo-radiotherapy, although associated with increased acute toxicity, has demonstrated to be the better strategy over sequential chemoradiotherapy, and it is to be considered a standard approach in patients with good performance status (0-1). However, the approach to locally advanced NSCLC and to chemo-radiotherapy regimens remains heterogeneous among oncologists, and clinical outcomes are yet disappointing. Thus, the search of new strategies is mandatory. The main fields of research aiming at improving the survival of locally advanced NSCLC patients are: the addition of further combination chemotherapy as induction or consolidation to concurrent chemo-radiotherapy, and the integration of molecularly targeted therapies into conventional chemo-radiotherapy regimens.     

A serum 25-hydroxyvitamin D concentration-associated genetic variant in DHCR7 interacts with type 2 diabetes status to influence subclinical atherosclerosis (measured by carotid intima–media thickness)

Aims/hypothesis

The findings of studies investigating whether or not low serum 25-hydroxyvitamin D [25(OH)D] concentration promotes development of atherosclerosis have been contradictory. The present study employed a Mendelian randomisation approach and carotid artery intima–media thickness (cIMT), a surrogate marker of coronary artery disease, to address this question.

Methods

The multicentre, longitudinal Carotid Intima–Media Thickness and IMT-Progression as Predictors of Vascular Events in a High-Risk European Population (IMPROVE) cohort study, which enrolled individuals with at least three cardiovascular risk factors and no history or symptoms of cardiovascular disease, was used for the present investigation. Participants underwent carotid ultrasound examination at baseline and at months 15 and 30. Six single nucleotide polymorphisms (SNPs) associated with serum 25(OH)D concentration in genome-wide association studies were identified and genotyped in 3,418 individuals, of whom 929 had type 2 diabetes.

Results

SNPs in the genes encoding vitamin D binding protein (GC; rs2282679 and rs7041) and 7-dehydrocholesterol reductase/NAD synthetase-1 (DHCR7; rs12785878 and rs3829251) were negatively associated with 25(OH)D levels. Effect sizes and significance of associations between SNPs and 25(OH)D levels differed between individuals with and without type 2 diabetes, although no significant interactions were observed. A SNP in DHCR7 interacted with type 2 diabetes to significantly influence progression of cIMT measures independent of 25(OH)D levels and established risk factors. Expression analysis demonstrated that this SNP modulates DHCR7 mRNA levels in aortic adventitia.

Conclusions/interpretation

SNPs in GC and DHCR7 were associated with serum levels of 25(OH)D, but only rs3829251 (DHCR7) influenced progression of subclinical atherosclerosis, as measured by cIMT, in a manner dependent on type 2 diabetes status but independent of 25(OH)D levels.     

Final analysis of the pilot trial of diaphragm pacing in amyotrophic lateral sclerosis with long-term follow-up: diaphragm pacing positively affects diaphragm respiration

Background

Respiratory insufficiency is the major cause of mortality in patients with amyotrophic lateral sclerosis or Lou Gehrig’s disease. This is the final report of the diaphragm pacing (DP) pilot trial.

Methods

Patients underwent laparoscopic diaphragm electrode implantations and subsequent conditioning of diaphragms. Serial respiratory function tests were performed in the initial year and followed until death.

Results

Sixteen patients were implanted with no perioperative or unanticipated device-related adverse events. There were 452 implant-months of follow-up. DP allowed greater movement of the diaphragm under fluoroscopy, increased muscle thickness, and decreased the decline in forced vital capacity. Median survival from implant was 19.7 months with the cause of death respiratory in only 31%.

Conclusions

Long-term analysis of DP in amyotrophic lateral sclerosis showed no safety issues and can positively influence diaphragm physiology and survival. This formed the initial basis for subsequent US Food and Drug Administration approval.     

Carotid intima-media thickness and bone turnover: the role of C-terminal telopeptide of type I collagen

Osteoporosis and vascular disease are commonly found together in elderly people. Several common mechanisms and risk factors have been suggested to contribute to the development of osteoporosis and atherosclerosis. The present cross-sectional study was performed to determine whether the degree of bone turnover is correlated to carotid intima-media thickness (CCA-IMT), as a marker of subclinical atherosclerosis. We selected 50 outpatients (mean age 71.7 ± 12.3), underwent to eco-Doppler evaluation of extracranial carotid tract, without history of calcium and/or vitamin D supplementation, or antireabsorptive therapy. CCA-IMT was measured by high-resolution B-mode ultrasonography. Bone turnover was evaluated by analysing serum levels of C-terminal telopeptide of type I collagen (sCTX), and bone-specific alkaline phosphatase. We also evaluated the vitamin D status by determination of the serum concentration of 25-hydroxyvitamin D [25(OH)D]. We found a prevalence of hypovitaminosis D [serum 25(OH)D levels <30 ng/mL, mean value 10.7 ± 5.8] of 91.8%, and an increased bone resorption, with mean sCTX levels higher than reference values (mean 1.18 ± 0.57 ng/mL). A significant positive correlation was found between CCA-IMT and age (r = 0.480, P = 0.001), erythrocyte sedimentation rate (ESR: r = 0.438, P = 0.001), high-sensitivity C-Reactive Protein (HsCRP: r = 0.482, P = 0.011), serum creatinine (r = 0.305, P = 0.031), and sCTX (r = 0.389, P = 0.006). In a multivariate linear regression, CCA-IMT was independently predicted by age (β = 0.34, P = 0.001), ESR (β = 0.37, P = 0.005), and sCTX (β = 0.32, P = 0.006). The preliminary results of our study seem to indicate that after adjustment for established cardiovascular risk factors, sCTX independently predict an increased CCA-IMT in the elderly population.     

Breast cancer as analyzed by the human tumor stem cell assay

Patients with primary and recurrent carcinomas of the breast were studied by the human tumor stem cell assay to determine if (1) colonies would form from breast cancer specimens, (2) growth in the culture would equate with aggressiveness of disease, (3) the assay would yield specific information on drug responsiveness, and (4) the assay would yield nonspecific information on drug responsiveness. Colony counts ranged from 0 to 363. There was no significant difference in median colony counts by pathologic stage of disease or site. Among stage IV patients presenting for treatment with primary disease, those with colony counts greater than 10 had a mortality rate of 4.7/1000 person-days; there were no deaths among those with colony counts less than or equal to 10 (P = 0.042). Stage IV patients presenting with recurrent disease showed no association between colony counts and survival (P = 0.53). No significant relationship between colony counts and disease-free intervals was observed among stages I, II, and III patients (P = 0.10). Drug sensitivity in vitro was found in 14% of the cultures with colony counts greater than or equal to 30. The only complete clinical responses in stage IV patients occurred in two patients with 0 colony counts. These data demonstrate that colonies grow from breast cancer specimens, that colony formation in vitro may be related to aggressiveness of growth in vivo in patients presenting with stage IV disease, that drug sensitivity is demonstrated in few cultures, and that patients with metastatic disease who have complete response to systemic therapy may be identified by lack of growth in the culture.