Effect of intermittent vitamin D3 on vascular function and symptoms in chronic fatigue syndrome--a randomised controlled trial.

BACKGROUND AND AIMS: Low 25-hydroxyvitamin D levels are common in patients with chronic fatigue syndrome; such patients also manifest impaired vascular health. We tested whether high-dose intermittent oral vitamin D therapy improved markers of vascular health and fatigue in patients with chronic fatigue syndrome. METHODS AND RESULTS: Parallel-group, double-blind, randomised placebo-controlled trial. Patients with chronic fatigue syndrome according to the Fukuda (1994) and Canadian (2003) criteria were randomised to receive 100,000 units oral vitamin D3 or matching placebo every 2 months for 6 months. The primary outcome was arterial stiffness measured using carotid-femoral pulse wave velocity at 6 months. Secondary outcomes included flow-mediated dilatation of the brachial artery, blood pressure, cholesterol, insulin resistance, markers of inflammation and oxidative stress, and the Piper Fatigue scale. As many as 50 participants were randomised; mean age 49 (SD 13) years, mean baseline pulse wave velocity 7.8 m/s (SD 2.3), mean baseline office blood pressure 128/78 (18/12) mmHg and mean baseline 25-hydroxyvitamin D level 46 (18) nmol/L. 25-hydroxyvitamin D levels increased by 22 nmol/L at 6 months in the treatment group relative to placebo. There was no effect of treatment on pulse wave velocity at 6 months (adjusted treatment effect 0.0 m/s; 95% CI -0.6 to 0.6; p = 0.93). No improvement was seen in other vascular and metabolic outcomes, or in the Piper Fatigue scale at 6 months (adjusted treatment effect 0.2 points; 95% CI -0.8 to 1.2; p = 0.73). CONCLUSION: High-dose oral vitamin D3 did not improve markers of vascular health or fatigue in patients with chronic fatigue syndrome. TRIAL REGISTRATION: www.controlled-trials.com, ISRCTN59927814.

Myocardial fibrosis and QTc are reduced following treatment with spironolactone or amiloride in stroke survivors: a randomised placebo-controlled cross-over trial.

INTRODUCTION: Myocardial fibrosis is dysrhythmogenic and may contribute to the high incidence of cardiac death in stroke survivors, especially if they have long QTc. We tested the hypothesis that procollagen-1-carboxy terminal peptide (P1CP), a biomarker of myocardial fibrosis, might be improved following treatment with spironolactone or amiloride in stroke survivors. We also tested the hypothesis that both drugs would shorten QTc. STUDY DESIGN: randomised, double-blinded, placebo-controlled, cross-over trial (spironolactone vs. amiloride vs. placebo). Duration of Study: 3 months (1 month per drug). Primary endpoints: P1CP, QTc RESULTS: 11 stroke survivors (5 female), aged 71 ± 4, BP 139/81 mmHg ± 20/11 mmHg, completed the study. Both spironolactone and amiloride significantly reduced P1CP [Spironolactone-Placebo = -24 ug/L, 95% CI = -40 to -6.9; Amiloride-Placebo = -28 ug/L, 95% CI = -44 to -11]. Spironolactone and amiloride both shortened QTc [Spironolactone vs. Placebo=-18 ms(1/2), 95% CI = -36 to -0.55; Amiloride vs Placebo = -25 ms(1/2), 95% CI = -42 to -7.5]. CONCLUSIONS: Procollagen-1-carboxy terminal peptide was reduced following treatment with spironolactone within a month. Further, this is the first study demonstrating amiloride could also improve myocardial fibrosis. The beneficial effects of both drugs on myocardial fibrosis, coupled with their effects on raising potassium translated to a shortening of QTc. Future studies should test the hypothesis that these drugs might reduce the risk of sudden cardiac death in stroke survivors.

A novel approach to measuring skin elasticity in systemic sclerosis: results from a pilot study.

OBJECTIVES: Systemic sclerosis (SSc) is characterized by progressive fibrosis of various organs, and causes hard, tethered, and inelastic skin. The modified Rodnan score is used to quantify skin involvement, but this method is subjective and user dependent. The aim of this study was to test the ability of a new skin torsion device to measure skin elasticity in patients with SSc. METHODS: The study included 16 female SSc patients and 58 healthy controls. Skin elasticity was assessed on the forearms and backs of the hands using a new hand-held device that gently rotates the skin for 15 s to a maximum of 40 deg, and measures the speed of rotation and the angle of rotation at 15 s. Total and localized modified Rodnan scores were also documented. RESULTS: Measurements produced by the skin torsion device had good intra-subject reproducibility, particularly in the control group. The SSc patients had significantly lower skin elasticity than an age-matched subgroup of control subjects, as determined by the median speed of rotation of the device in the hands (1.91 vs. 2.60 deg/s, p < 0.0001) and forearms (1.84 vs. 2.46 deg/s, p < 0.0001), and the rotation at 15 s in the hands (28.6 vs. 39.0 deg, p < 0.0001) and forearms (27.6 vs. 36.9 deg, p < 0.0001). The presence of SSc disease was the only independent predictor of skin elasticity. CONCLUSIONS: This pilot study has shown the potential value of a new skin torsion device to assess skin involvement in patients with SSc.

Macrovascular disease in systemic sclerosis: the tip of an iceberg?

This mini review evaluates mortality in SSc and provides a literature review concluding that premature death does occur in this population. However, there has been a changing spectrum of cause of death over the past three decades, with interstitial lung disease now being the commonest cause of SSc-related mortality. Cardiovascular (CV) mortality and events also contribute to the premature mortality seen in these patients, and this contention is supported by epidemiological studies, and further underpinned by a plethora of increased biomarkers for CV disease and events. Thus, macrovascular disease does occur in these patients, and is likely to contribute to mortality. It remains to be seen whether addressing conventional risk factors will attenuate CV disease in this population.

B-type natriuretic peptide identifies silent myocardial ischaemia in stroke survivors.

OBJECTIVE: To test the hypothesis that B-type natriuretic peptide (BNP) predicts reversible myocardial ischaemia in stroke survivors who do not have chest pain or previous myocardial infarction. METHODS: 56 stroke survivors (mean (SE) age 68 (8) years) underwent tetrofosmin myocardial perfusion scanning with dipyridamole as the stressor. The degree of ischaemia was assessed by a scoring system (out of 64) by an experienced observer blinded to the results of BNP. RESULTS: In the whole cohort, BNP was significantly correlated with the degree of myocardial ischaemia on stress scanning (Spearman's r = -0.475, p < 0.001). BNP also correlated with the degree of reversible ischaemia (stress score - rest score; Spearman's r = 0.28, two tailed p = 0.049). In the cohort who did not have left ventricular systolic dysfunction (n = 44), BNP remained higher in patients with relevant myocardial ischaemia (mean (SE) BNP 20.9 pg/ml, 95% confidence interval (CI) 15.2 to 26.5 v 12.2 pg/ml, 95% CI 5.95 to 18.5; p = 0.046); 33 of the 44 patients had no chest pain or history of myocardial infarction. The relation between resting BNP and both inducible ischaemia and dipyridamole stress score remained significant (Spearman's r = 0.37 and -0.38, respectively). CONCLUSIONS: BNP correlates with the degree of reversible myocardial ischaemia in patients who do not have chest pain or a history of myocardial infarction or evidence of left ventricular systolic dysfunction. Stroke survivors with a high BNP deserve further investigations to rule out significant reversible myocardial ischaemia, in order to reduce their risk of cardiac death.

Spectrum of cardiac abnormalities associated with long QT in stroke survivors.

OBJECTIVES: To find out what spectrum of cardiac abnormalities are found in those stroke survivors who can be deemed to be at high cardiac risk by their having long QT. METHODS: 202 patients with good recovery from a cerebrovascular event occurring at least one month previously were recruited into a prospective epidemiological study. These stroke survivors underwent a battery of cardiac investigations including 12 lead ECG, echocardiography, myocardial perfusion scanning, and heart rate variability assessment. The ECGs were digitised by a single observer blinded to the blood pressure and other investigations of the patients. The maximum heart rate corrected QT interval (QTc max) in the 12 lead ECG was derived by Bazett's formula. RESULTS: Prolonged QTc max significantly correlated with increasing blood pressure, left ventricular mass index, and depressed heart rate variability. As the number of cardiac abnormalities increased, QTc max became more prolonged. CONCLUSIONS: Long QT is significantly associated with left ventricular mass index even after adjustment for both systolic and diastolic blood pressures. Long QT was also associated with the total cardiac disease burden. These two observations may explain why stroke survivors with long QTc max were at greater risk of cardiac death.