Endothelium-dependent vasodilation, insulin resistance and the metabolic syndrome in an elderly cohort: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study

BackgroundOnly a few previous studies have investigated endothelium-dependent vasodilation in the metabolic syndrome (MetS). In the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) study, different techniques to assess vasodilation in conduit and resistance arteries were evaluated in relation to the MetS and insulin resistance.MethodsIn this population-based study, 1016 subjects aged 70 were evaluated by the invasive forearm technique with acetylcholine (EDV), brachial artery ultrasound to assess flow-mediated vasodilation (FMD) and pulse wave analysis with a beta-2 receptor agonist challenge, terbutaline.ResultsEDV was lower in subjects with the MetS (NECP/ATP III-criteria, prevalence 23%) compared to those without (p < 0.0001), and declined with increasing number of MetS criteria (p < 0.0001), after adjustment for coronary heart disease, stroke and cardiovascular medication. Also a reduced pulse wave response (p = 0.015), but not FMD (p = 0.64), was seen in those with the MetS. EDV and the pulse wave response, but not FMD, were inversely related to insulin resistance evaluated by the HOMA index. Also endothelium-independent vasodilation (EIDV) induced by intra-brachial infusion of sodium nitroprusside was impaired in subjects with MetS and in insulin resistance.ConclusionsVasodilation evaluated with the invasive forearm technique and pulse wave analysis with a beta-2 agonist, but not FMD, was reduced in elderly subjects with the MetS and was related to insulin resistance. Also EIDV showed the same pattern, suggesting a general deterioration in vasoreactivity mainly in resistance arteries in elderly subjects with the MetS.     

Skeletal muscle magnesium content is correlated with plasma glucose concentration in patients with essential hypertension treated with lisinopril or bendrofluazide

The association between change in glucose metabolism and change in skeletal muscle magnesium (Mg) concentration induced by antihypertensive treatment was evaluated in 37 patients with essential hypertension randomly treated with either lisinopril or bendrofluazide. Before and after 6 months of treatment, skeletal muscle biopsies were performed, glucose tolerance was determined by oral (OGTT) and intravenous glucose tolerance tests (IVGTT), and insulin sensitivity was assessed by the hyperinsulinemic euglycemic clamp technique. An inverse relationship was found between the treatment-induced change in fasting plasma glucose concentration and change in skeletal muscle Mg concentration (r = -0.39, P < .05). However, there was no significant correlation between skeletal muscle Mg content and either insulin sensitivity measured by the hyperinsulinemic euglycemic clamp test or glucose tolerance evaluated by IVGTT and OGTT. In conclusion, an increased circulating glucose concentration was correlated with a decreased Mg concentration in skeletal muscle during antihypertensive treatment. However, the Mg concentration in skeletal muscle did not significantly predict the insulin sensitivity or glucose tolerance.     

Inflammation, as measured by the erythrocyte sedimentation rate, is an independent predictor for the development of heart failure

OBJECTIVES: Our objective was to explore inflammation, measured as erythrocyte sedimentation rate (ESR), as a predictor for the development of heart failure (HF). BACKGROUND: In recent years, evidence of the importance of inflammation in the pathophysiology of HF has emerged, and various inflammatory markers have been found to predict future HF. Erythrocyte sedimentation rate is an inexpensive and easily accessible marker of systemic inflammation, but to this date it is unknown whether ESR predicts subsequent HF. METHODS: In a community-based prospective study of 2,314 middle-aged men free from HF, myocardial infarction, and valvular disease at baseline, ESR was analyzed in multivariable models together with established risk factors for HF (hypertension, diabetes, electrocardiographic left ventricular hypertrophy, smoking, obesity, and serum cholesterol) and hematocrit. RESULTS: A total of 282 men developed HF during a median follow-up time of 30 years. In Cox proportional hazards analyses, ESR was an independent predictor of HF (hazard ratio 1.46 for highest quartile vs. the lowest, 95% confidence interval 1.04 to 2.06). This observation remained significant when also adjusting for interim myocardial infarction during follow-up. CONCLUSIONS: Erythrocyte sedimentation rate was a significant predictor of HF, independent of established risk factors for HF, and interim myocardial infarction after three decades of follow-up in a population-based sample of middle-aged men. Our findings indicate that inflammation occurs early in the process leading to HF and that ESR could be used to evaluate this process.     

What parameters are relevant for the histological diagnosis of gastroesophageal reflux disease without Barrett's mucosa?

BACKGROUND/AIMS: There are still ongoing controversies as to which histological parameters allow the diagnosis of gastroesophageal reflux disease (GERD). The aim of the present analysis was to relate histological changes of the esophageal squamous epithelium to different severities of GERD. METHODS: Data were obtained from patients participating in the ProGERD study, who had either erosive reflux disease (ERD, n = 3,245) or non-erosive reflux disease (NERD, n = 2,970). 1,475 patients fulfilled our requirement of having complete biopsy data from two sites (2 cm above the z-line and at the z-line). Changes in the squamous epithelium were assessed by measuring the thickness of the basal cell layer and elongation of the papillae as a percentage of the whole epithelial thickness and counting interepithelial inflammatory cells. RESULTS: The most useful parameters for histological assessment of GERD (given as means, 2 cm above the z-line and at the z-line, respectively) were elongation of the papillae: NERD 40.7 and 48.9%; ERD 46.1 and 54.9% and basal cell hyperplasia: NERD 12.7 and 17.9%; ERD 15.7 and 23.0%. The occurrence of intraepithelial lymphocytic infiltrates, however, is dependent on the severity of GERD, and they are more common than neutrophilic and eosinophilic granulocytes. CONCLUSION: This study shows that both NERD and ERD can be diagnosed histologically if biopsies are obtained from the distal esophagus or from the z-line. Intraepithelial inflammatory cells are rare and show a high specificity, but very low sensitivity.     

Characteristics and outcomes of recurrent atrial fibrillation after prior failed pulmonary vein isolation

Journal of Interventional Cardiac Electrophysiology - The mechanisms for atrial fibrillation (AF) recurrence after pulmonary vein isolation (PVI) catheter ablation are unclear. Non-PV organized...     

Comparison of once-daily intravenous and oral omeprazole on pentagastrin-stimulated acid secretion in duodenal ulcer patients.

The effect of 5 days of once-daily dosing with 20 mg p.o. and 40 mg i.v. omeprazole on pentagastrin-stimulated acid secretion was studied in 8 patients with duodenal ulcer. In addition they also received a 10-mg i.v. dose on day 6 during the oral treatment period. The antisecretory effect was measured 6-7 h after dose at a time point when maximal inhibition during the dosing interval is anticipated. The median percent inhibition of peak acid output (PAO) markedly increased from 43% on day 1 to 100% on day 5 during treatment with 20 mg p.o. The first 40-mg i.v. dose produced a median inhibition of 98% of PAO already on day 1. After 5 days of dosing, the inhibition had increased to 100%. On the other hand, a 10-mg i.v. dose could essentially maintain the degree of PAO reduction reached after 5 days of oral treatment. Plasma omeprazole concentrations increased during repeated dosing both with 20 mg p.o. and 40 mg i.v.     

24-hour intragastric acidity and plasma gastrin after omeprazole treatment and after proximal gastric vagotomy in duodenal ulcer patients

The relationship between suppressed gastric acidity and the increase in plasma gastrin levels after pharmacological and surgical treatment of peptic ulcer disease were compared in this study. Eight patients with chronic duodenal ulcer and referred for proximal gastric vagotomy were studied. 24-hour intragastric acidity and plasma gastrin levels were investigated in the same patients on three consecutive occasions: preentry without any treatment; after 4 weeks of administration of 20 mg of omeprazole daily, and 4-6 months after proximal gastric vagotomy. Intragastric acidity was slightly more reduced by omeprazole (94%) than after proximal gastric vagotomy (78%), with no difference found during the day or night with either. Plasma gastrin levels increased slightly more after proximal gastric vagotomy [284% (median, 2120 pmol.h/L; range, 733-2831 pmol.h/L)] than after omeprazole administration [186% (median, 1586 pmol.h/L; range, 495-2573 pmol.h/L)]. There is strong evidence that the increased plasma gastrin concentration following omeprazole treatment is caused by the reduced intragastric acidity. The slight increase in plasma gastrin concentration following proximal gastric vagotomy despite a lesser reduction in intragastric acidity may be the result of additional effects on gastrin release by the vagotomy. Both treatments resulted in a modest increase in plasma levels of gastrin that were far below the gastrin levels observed in achlorhydric patients, e.g., patients with pernicious anemia.