Association between VO2 peak estimated by a 1-km treadmill walk and mortality. A 10-year follow-up study in patients with cardiovascular disease

Purpose

The aim of this study is to assess the association between peak oxygen uptake (VO₂ peak), determined using a perceptually regulated 1-km walking test (1 k-TWT), and all-cause mortality in cardiac patients.

Methods

1255 male patients, aged 25–85 years, completed a moderate 1 k-TWT to estimate VO₂ peak. Subjects were followed for all-cause mortality for up to 10 years. Cox proportional hazard models were employed to determine variables associated with mortality. Based on the estimated VO₂ peak, the sample was subdivided into quartiles and mortality risks were calculated. To assess the discriminatory accuracy of the estimated VO₂ peak for estimating survival, receiver-operating-characteristics curves were constructed.

Results

During a median 8.2 year follow-up, a total of 141 deaths from any cause occurred, yielding an average annual mortality of 1.4%. The strongest predictor of all-cause mortality was the estimated VO₂ peak (c-statistic 0.71, 95% confidence intervals: 0.69–0.74, P < 0.0001). Survival decreased in a graded fashion from the highest estimated VO₂ peak quartile to the lowest quartile. Compared to the lowest quartile, the hazard ratios (95% confidence intervals) for the second, third, and fourth quartiles were 0.77 (0.35–1.33), 0.43 (0.20–0.91), and 0.16 (0.05–0.54) respectively (P for trend < 0.0001). An 89% reduction in mortality risk was observed among a subset of subjects in the fittest quartile who improved their estimated VO₂ peak over the follow-up period relative to subjects in the least fit quartile who did not improve.

Conclusion

VO₂ peak estimated by a novel 1 k-TWT predicts survival in subjects with stable cardiovascular disease.     

Synthetic cathinones: an evolving class of new psychoactive substances

Abstract

Synthetic cathinones (SCat) are amphetamine-like psychostimulants that emerged onto drug markets as “legal” alternatives to illicit drugs such as ecstasy, cocaine, and amphetamines. Usually they are sold as “bath salts,” “plant food,” or “research chemicals,” and rapidly gained popularity amongst drugs users due to their potency, low cost, and availability. In addition, internet drug sales have been replacing the old way of supplying drugs of abuse, contributing to their rapid spread. Despite the legislative efforts to control SCat, new derivatives continue to emerge on the recreational drugs market and their abuse still represents a serious public health issue. To date, about 150 SCat have been identified on the clandestine drugs market, which are one of the largest groups of new psychoactive substances (NPS) monitored by the United Nations Office on Drugs and Crime and the European Monitoring Center for Drugs and Drug Addiction. Similar to the classical stimulants, SCat affect the levels of catecholamines in the central nervous system, which results in their psychological, behavioral and toxic effects. Generally, the effects of SCat greatly differ from drug to drug and relatively little information is available about their pharmacology. The present work provides a review on the development of SCat as substances of abuse, current patterns of abuse and their legal status, chemical classification, known mechanisms of action, and their toxicological effects.     

Vitamin D in “early” primary Sjögren’s syndrome: does it play a role in influencing disease phenotypes?

Beyond its well-established role in the maintenance of mineral homeostasis, 25-OH-vitamin D deficiency seems to be involved in the development and severity of several autoimmune diseases. To date, contrasting data have been reported regarding the presence of hypovitaminosis D in primary Sjögren’s syndrome (pSS). To assess the prevalence of hypovitaminosis D in pSS at an early stage of the disease and to evaluate its impact on pSS clinical manifestations and disease activity, unselected consecutive subjects with recent onset dry mouth and/or dry eyes who underwent a comprehensive diagnostic algorithm for pSS (AECG criteria) were prospectively included in the study. The levels of 25[OH]-D3 were measured by monoclonal antibody immunoradiometric assay. Conditions of 25[OH]-D3 severe deficiency, deficiency, and insufficiency were defined as levels <10, <20, and 20–30 ng/ml, respectively, and their frequencies were investigated in pSS patients and controls. The levels of 25[OH]-D3 were also correlated with patients’ demographic, clinical, and serologic features. Seventy-six consecutive females were included: 30/76 patients fulfilled the AECG criteria for pSS. The remaining 46/76 patients represented the control group. No statistical differences were found in the serum levels of 25[OH]-D3 between pSS patients [median levels = 20 ng/ml (IQR 9.3–26)] and controls [median levels = 22.5 ng/ml (IQR 15.6–33)]. In particular, the frequency of 25[OH]-D3 severe deficiency was not significantly different in patients with pSS when compared to controls (23 vs. 17.4 %, p value = 0.24). We found a significant correlation between serum 25[OH]-D3 levels and white blood cells count (r = 0.29, p = 0.01). More specifically, leukocytopenia was significantly associated with 25[OH]-D3 severe deficiency, being documented in 40 % of the subjects with a 25[OH]-D3 severe deficiency and in 11 % of the subjects without a severe vitamin D deficiency (p = 0.02). We did not observe any further association or correlation between hypovitaminosis D and pSS glandular and extra-glandular features. Although the role of hypovitaminosis D in pSS pathogenesis remains controversial, the results of this study encourage the assessment of vitamin D in specific pSS subsets that could mostly benefit from a supplementation.     

Endoscopic Bilio-Duodenal Bypass: Outcomes of Primary and Revision Efficacy of Combined Metallic Stents in Malignant Duodenal and Biliary Obstructions

Background

Self-expandable metal stents (SEMSs) can be used for palliation of combined malignant biliary and duodenal obstructions. However, the results of the concomitant stent placement for the duration of the patients’ lives, as well as the need for and efficacy of endoscopic revision, are unclear.

Aim

This study evaluated the clinical effectiveness of SEMS placement for combined biliary and duodenal obstructions throughout the patients’ lives and the need for endoscopic revision.

Methods

This study is a retrospective multicenter study of 50 consecutive patients who underwent simultaneous or sequential SEMS placement for malignant biliary and duodenal obstructions. The data were collected to analyze the sustained relief of obstructive symptoms until the patients’ death and the efficacy of endoscopic revision, as well as stent patency, adverse events, survival and prognostic factors for stent patency.

Results

Technical and immediate clinical success was achieved in all of the patients. Duodenal stricture occurred before the papilla in 35 patients (70 %), involved the papilla in 11 patients (22 %) and was observed distal to the papilla in four patients (8 %). Initial biliary stenting was performed endoscopically in 42 patients (84 %) and percutaneously in eight patients. After combined stenting, 30 patients (60 %) required no additional intervention until the time of their death. The remaining 20 patients were successfully treated using endoscopic stent reinsertion: nine patients needed biliary revision, three patients needed duodenal restenting and eight patients needed both biliary and duodenal reinsertion. The median duodenal stent patency and median biliary stent patency were 34 and 27 weeks, respectively. The median survival after combined stent placement was 18 weeks. A Cox multivariate analysis showed that duodenal stent obstruction after combined stenting was a risk factor for biliary stent obstruction (hazard ratio 6.85; 95 % confidence interval 1.43–198.98; P = 0.025).

Conclusions

Endoscopic bilio-duodenal bypass is clinically effective, and the majority of the patients need no additional intervention until their death. Endoscopic revision is feasible and has a high success rate.     

Modulation of cardiac mitochondrial permeability transition and apoptotic signaling by endurance training and intermittent hypobaric hypoxia

Background

Modulation of the mitochondrial permeability transition pore (MPTP) and inhibition of the apoptotic signaling are critically associated with the cardioprotective phenotypes afforded by both intermittent hypobaric-hypoxia (IHH) and endurance-training (ET). We recently proposed that IHH and ET improve cardiac function and basic mitochondrial capacity, although without showing addictive effects. Here we investigate whether a combination of IHH and ET alters cardiac mitochondrial vulnerability to MPTP and related apoptotic signaling.

Methods

Male Wistar rats were divided into normoxic-sedentary (NS), normoxic-exercised (NE, 1 h/day/5 week treadmill-running), hypoxic-sedentary (HS, 6000 m, 5 h/day/5 weeks) and hypoxic-exercised (HE) to study susceptibility to calcium-induced cardiac MPTP opening. Mitochondrial cyclophilin D (CypD), adenine nucleotide translocator (ANT), Bax and Bcl-2 protein contents were semi-quantified by Western blotting. Cardiac caspase 3-, 8- and 9-like activities were measured. Mitochondrial aconitase and superoxide dismutase (MnSOD) activity and malondialdehyde (MDA) and sulphydryl group (–SH) content were determined.

Results

Susceptibility to MPTP decreased in NE and HS vs. NS and even further in HE. The ANT content increased in HE vs. NS. Bcl-2/Bax ratio increased in NE and HS compared to NS. Decreased activities in tissue caspase 3-like (HE vs. NS) and caspase 9-like (HS and HE vs. NS) were observed. Mitochondrial aconitase increased in NE and HS vs. NS. No alterations between groups were observed for caspase 8-like activity, MnSOD, CypD, MDA and –SH.

Conclusions

Data confirm that IHH and ET modulate cardiac mitochondria to a protective phenotype characterized by decreased MPTP induction and apoptotic signaling, although without visible addictive effects as initially hypothesized.     

Importancia de la carga vascular previa en la mortalidad intrahospitalaria y a largo plazo de pacientes con infarto de miocardio y segmento ST elevado

Introduction and objectives

Patients with a current acute coronary syndrome and previous ischemic heart disease, peripheral arterial disease, or cerebrovascular disease are reported to have a poorer outcome than those without these previous conditions. It is uncertain whether this association with outcome is observed at long-term follow-up.

Methods

Prospective observational study, including 4247 patients with ST-segment elevation myocardial infarction. Detailed clinical data and information on previous ischemic heart disease, peripheral arterial disease, and cerebrovascular disease («vascular burden») were recorded. Multivariate models were performed for in-hospital and long-term (median, 7.2 years) all-cause mortality.

Results

One vascular territory was affected in 1131 (26.6%) patients and ≥ 2 territories in 221 (5.2%). The total in-hospital mortality rate was 12.3% and the long-term incidence density was 3.5 deaths per 100 patient-years. A background of previous ischemic heart disease (odds ratio = 0.83; P = .35), peripheral arterial disease (odds ratio = 1.30; P=.34), or cerebrovascular disease (stroke) (odds ratio = 1.15; P = .59) was not independently predictive of in-hospital death. In an adjusted model, previous cerebrovascular disease and previous peripheral arterial disease were both predictors of mortality at long-term follow-up (hazard ratio = 1.57; P < .001; and hazard ratio = 1.34; P = .001; respectively). Patients with ≥ 2 diseased vascular territories showed higher long-term mortality (hazard ratio = 2.35; P < .001), but not higher in-hospital mortality (odds ratio = 1.07; P = .844).

Conclusions

In patients with a diagnosis of ST-segment elevation acute myocardial infarction, the previous vascular burden determines greater long-term mortality. Considered individually, previous cerebrovascular disease and peripheral arterial disease were predictors of mortality at long-term after hospital discharge.Full English text available from: www.revespcardiol.org/en