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Open access

Hamidreza Mani, Yogini Chudasama, Michelle Hadjiconstantinou, Danielle H Bodicoat, Charlotte Edwardson, Miles J Levy, Laura J Gray, Janette Barnett, Heather Daly, Trevor A Howlett, Kamlesh Khunti, and Melanie J Davies

Objective

To evaluate the effectiveness of a structured education programmes in women with polycystic ovary syndrome (PCOS).

Methods

Single-centre, randomised controlled trial, testing a single exposure to a group-based, face-to-face, structured education programme. Inclusion criteria were women with PCOS, aged 18–49 years inclusive and body mass index ≥23 kg/m2 for black and minority ethnicities or ≥25 kg/m2 for white Europeans. Primary outcome was step-count/day at 12 months. Secondary outcomes included indices of physical activity, cardiovascular risk factors, quality of life (QoL) and illness perception (IP).

Results

161 women were included (78 control, 83 intervention); 69% white; mean age 33.4 (s.d. 7.6) years, of whom 100 (48 intervention; 52 control) attended their 12-month visit (38% attrition). 77% of the intervention arm attended the education programme. No significant change in step-count was observed at 12 months (mean difference: +351 steps/day (95% confidence interval −481, +1183); P = 0.40). No differences were found in biochemical or anthropometric outcomes. The education programme improved participants’ IP in 2 dimensions: understanding their PCOS (P < 0.001) and sense of control (P < 0.01) and improved QoL in 3 dimensions: emotions (P < 0.05), fertility (P < 0.05), weight (P < 0.01) and general mental well-being (P < 0.01).

Discussion

A single exposure to structured education programme did not increase physical activity or improve biochemical markers in overweight and obese women with PCOS. However, providing a structured education in parallel to routine medical treatment can be beneficial for participants’ understanding of their condition, reducing their anxiety and improving their QoL.

Open access

Julia Kubiak, Per Medbøe Thorsby, Elena Kamycheva, and Rolf Jorde

Objective

Low serum 25(OH)D levels are associated with cardiovascular disease (CVD) and some of its risk factors. However, in interventional studies, the effects of vitamin D supplementation have been uncertain, possibly due to inclusion of vitamin D-sufficient subjects. Our aim was therefore to examine effects of vitamin D supplementation on CVD risk factors in vitamin D-insufficient subjects.

Design

Double-blinded randomized controlled trial.

Methods

A 4-month interventional study with high-dose vitamin D (100,000 IU loading dose, followed by 20,000 IU/week) or placebo with measurements of blood pressure, lipids (total-, LDL- and HDL-cholesterol, triglycerides, apolipoproteins A1 and B), and glucose metabolism parameters (blood glucose, HbA1c, serum human receptors for advanced glycation end products (sRAGE), insulin, C-peptide and HOMA-IR).

Results

A total of 422 subjects with mean serum 25(OH)D level 34 nmol/L were included, with 411 subjects completing the study. Serum 25(OH)D levels increased with 56 nmol/L and decreased with 4 nmol/L in the vitamin D and placebo group, respectively. We found no statistically significant differences between the two groups in any of the measured CVD risk factors, except for a minor increase in sRAGE in the vitamin D group. Stratified analyses of subjects with low baseline serum 25(OH)D levels alone, or combined with blood pressure, lipid and HOMA-IR values above the median for the cohort, did not skew the results in favour of vitamin D supplementation.

Conclusion

Supplementation with vitamin D in subjects with baseline vitamin D insufficiency does not improve CVD risk factor profile.

Open access

Stine A Holmboe, Ravi Jasuja, Brian Lawney, Lærke Priskorn, Niels Joergensen, Allan Linneberg, Tina Kold Jensen, Niels Erik Skakkebæk, Anders Juul, and Anna-Maria Andersson

Objective

Calculating the free testosterone level has gained increasing interest and different indirect algorithms have been suggested. The objective was to compare free androgen index (FAI), free testosterone estimated using the linear binding model (Vermeulen: cFTV) and the binding framework accounting for allosterically coupled SHBG monomers (Zakharov: cFTZ) in relation to cardiometabolic conditions.

Design

A prospective cohort study including 5350 men, aged 30–70 years, participating in population-based surveys (MONICA I–III and Inter99) from 1982 to 2001 and followed until December 2012 with baseline and follow-up information on cardiometabolic parameters and vital status.

Results

Using age-standardized hormone levels, FAI was higher among men with baseline cardiometabolic conditions, whereas cFTV and cFTZ levels were lower compared to men without these conditions as also seen for total testosterone. Men in highest quartiles of cFTV or cFTZ had lower risk of developing type 2 diabetes (cFTV: HR = 0.74 (0.49–1.10), cFTZ: HR = 0.59 (0.39–0.91)) than men in lowest quartile. In contrast, men with highest levels of FAI had a 74% (1.17–2.59) increased risk of developing type 2 diabetes compared to men in lowest quartile.

Conclusion

The association of estimated free testosterone and the studied outcomes differ depending on algorithm used. cFTV and cFTZ showed similar associations to baseline and long-term cardiometabolic parameters. In contrast, an empiric ratio, FAI, showed opposite associations to several of the examined parameters and may reflect limited clinical utility.

Open access

T L C Wolters, C D C C van der Heijden, N van Leeuwen, B T P Hijmans-Kersten, M G Netea, J W A Smit, D H J Thijssen, A R M M Hermus, N P Riksen, and R T Netea-Maier

Objective

Acromegaly is characterized by an excess of growth hormone (GH) and insulin-like growth factor 1 (IGF1). Cardiovascular disease (CVD) risk factors are common in acromegaly and often persist after treatment. Both acute and long-lasting pro-inflammatory effects have been attributed to IGF1. Therefore, we hypothesized that inflammation persists in treated acromegaly and may contribute to CVD risk.

Methods

In this cross-sectional study, we assessed cardiovascular structure and function, and inflammatory parameters in treated acromegaly patients. Immune cell populations and inflammatory markers were assessed in peripheral blood from 71 treated acromegaly patients (with controlled or uncontrolled disease) and 41 matched controls. Whole blood (WB) was stimulated with Toll-like receptor ligands. In a subgroup of 21 controls and 33 patients with controlled disease, vascular ultrasound measurements were performed.

Results

Leukocyte counts were lower in patients with controlled acromegaly compared to patients with uncontrolled acromegaly and controls. Circulating IL18 concentrations were lower in patients; concentrations of other inflammatory mediators were comparable with controls. In stimulated WB, cytokine production was skewed toward inflammation in patients, most pronounced in those with uncontrolled disease. Vascular measurements in controlled patients showed endothelial dysfunction as indicated by a lower flow-mediated dilatation/nitroglycerine-mediated dilatation ratio. Surprisingly, pulse wave analysis and pulse wave velocity, both markers of endothelial dysfunction, were lower in patients, whereas intima-media thickness did not differ.

Conclusions

Despite treatment, acromegaly patients display persistent inflammatory changes and endothelial dysfunction, which may contribute to CVD risk and development of CVD.

Open access

Chunliang Yang, Junyi Li, Fei Sun, Haifeng Zhou, Jia Yang, and Chao Yang

Hyperglycemia is the consequence of blood glucose dysregulation and a driving force of diabetic complications including retinopathy, nephropathy and cardiovascular diseases. The serum and glucocorticoid inducible kinase-1 (SGK1) has been suggested in the modulation of various pathophysiological activities. However, the role of SGK1 in blood glucose homeostasis remains less appreciated. In this review, we intend to summarize the function of SGK1 in glucose level regulation and to examine the evidence supporting the therapeutic potential of SGK1 inhibitors in hyperglycemia. Ample evidence points to the controversial roles of SGK1 in pancreatic insulin secretion and peripheral insulin sensitivity, which reflects the complex interplay between SGK1 activation and blood glucose fluctuation. Furthermore, SGK1 is engaged in glucose absorption and excretion in intestine and kidney and participates in the progression of hyperglycemia-induced secondary organ damage. As a net effect, blockage of SGK1 activation via either pharmacological inhibition or genetic manipulation seems to be helpful in glucose control at varying diabetic stages.

Open access

Jian Ding, Yan Kang, Yuqin Fan, and Qi Chen

Objective

Preeclampsia (PE) is a complication affecting pregnant women worldwide, which usually manifests as severe maternal hypertension. Resveratrol (RESV), a naturally existing polyphenol, is known to exhibit beneficial effects in cardiovascular disease including hypertension. We evaluated the outcome of treatment combining oral nifedipine (NIFE) and RESV against PE.

Design and methods

Using a randomized group assignment, 400 PE patients were enrolled and received oral treatments of either NIFE + RESV or NIFE + placebo. Primary endpoints were defined as time to control blood pressure and time before a new hypertensive crisis. Secondary endpoints were defined as the number of doses needed to control blood pressure, maternal and neonatal adverse effects.

Results

Compared with the NIFE + placebo group, the time needed to control blood pressure was significantly reduced in NIFE + RESV group, while time before a new hypertensive crisis was greatly delayed in NIFE + RESV group. The number of treatment doses needed to control blood pressure was also categorically lower in NIFE + RESV group. No differences in maternal or neonatal adverse effects were observed between the two treatment groups.

Conclusion

Our data support the potential of RESV as a safe and effective adjuvant of oral NIFE to attenuate hypertensive symptoms among PE patients.

Open access

Panagiotis Anagnostis, Irene Lambrinoudaki, John C Stevenson, and Dimitrios G Goulis

Cardiovascular disease (CVD) is of major concern in women entering menopause. The changing hormonal milieu predisposes them to increased CVD risk, due to a constellation of risk factors, such as visceral obesity, atherogenic dyslipidemia, dysregulation in glucose homeostasis, non-alcoholic fatty liver disease and arterial hypertension. However, an independent association of menopause per se with increased risk of CVD events has only been proven for early menopause (<45 years). Menopausal hormone therapy (MHT) ameliorates most of the CVD risk factors mentioned above. Transdermal estrogens are the preferable regimen, since they do not increase triglyceride concentrations and they are not associated with increased risk of venous thromboembolic events (VTE). Although administration of MHT should be considered on an individual basis, MHT may reduce CVD morbidity and mortality, if commenced during the early postmenopausal period (<60 years or within ten years since the last menstrual period). In women with premature ovarian insufficiency (POI), MHT should be administered at least until the average age of menopause (50–52 years). MHT is contraindicated in women with a history of VTE and is not currently recommended for the sole purpose of CVD prevention. The risk of breast cancer associated with MHT is generally low and is mainly conferred by the progestogen. Micronized progesterone and dydrogesterone are associated with lower risk compared to other progestogens.

Open access

Jan Calissendorff and Henrik Falhammar

Background

Graves’ disease is a common cause of hyperthyroidism. Three therapies have been used for decades: pharmacologic therapy, surgery and radioiodine. In case of adverse events, especially agranulocytosis or hepatotoxicity, pre-treatment with Lugol’s solution containing iodine/potassium iodide to induce euthyroidism before surgery could be advocated, but this has rarely been reported.

Methods

All patients hospitalised due to uncontrolled hyperthyroidism at the Karolinska University Hospital 2005–2015 and treated with Lugol’s solution were included. All electronic files were carefully reviewed manually, with focus on the cause of treatment and admission, demographic data, and effects of iodine on thyroid hormone levels and pulse frequency.

Results

Twenty-seven patients were included. Lugol’s solution had been chosen due to agranulocytosis in 9 (33%), hepatotoxicity in 2 (7%), other side effects in 11 (41%) and poor adherence to medication in 5 (19%). Levels of free T4, free T3 and heart rate decreased significantly after 5–9 days of iodine therapy (free T4 53–20 pmol/L, P = 0.0002; free T3 20–6.5 pmol/L, P = 0.04; heart rate 87–76 beats/min P = 0.0007), whereas TSH remained unchanged. Side effects were noted in 4 (15%) (rash n = 2, rash and vomiting n = 1, swelling of fingers n = 1). Thyroidectomy was performed in 26 patients (96%) and one was treated with radioiodine; all treatments were without serious complications.

Conclusion

Treatment of uncontrolled hyperthyroidism with Lugol’s solution before definitive treatment is safe and it decreases thyroid hormone levels and heart rate. Side effects were limited. Lugol’s solution could be recommended pre-operatively in Graves’ disease with failed medical treatment, especially if side effects to anti-thyroid drugs have occurred.

Open access

Alexander Tacey, Lewan Parker, Bu B Yeap, John Joseph, Ee M Lim, Andrew Garnham, David L Hare, Tara Brennan-Speranza, and Itamar Levinger

The aim of this study was to investigate the effect of a single dose of prednisolone on (A) high-intensity interval cycling performance and (B) post-exercise metabolic, hormonal and haematological responses. Nine young men participated in this double-blind, randomised, cross-over study. The participants completed exercise sessions (4 × 4 min cycling bouts at 90–95% of peak heart rate), 12 h after ingesting prednisolone (20 mg) or placebo. Work load was adjusted to maintain the same relative heart rate between the sessions. Exercise performance was measured as total work performed. Blood samples were taken at rest, immediately post exercise and up to 3 h post exercise. Prednisolone ingestion decreased total work performed by 5% (P < 0.05). Baseline blood glucose was elevated following prednisolone compared to placebo (P < 0.001). Three hours post exercise, blood glucose in the prednisolone trial was reduced to a level equivalent to the baseline concentration in the placebo trial (P > 0.05). Prednisolone suppressed the increase in blood lactate immediately post exercise (P < 0.05). Total white blood cell count was elevated at all time-points with prednisolone (P < 0.01). Androgens and sex hormone-binding globulin were elevated immediately after exercise, irrespective of prednisolone or placebo. In contrast, prednisolone significantly reduced the ratio of testosterone/luteinizing hormone (P < 0.01). Acute prednisolone treatment impairs high-intensity interval cycling performance and alters metabolic and haematological parameters in healthy young men. Exercise may be an effective tool to minimise the effect of prednisolone on blood glucose levels.

Open access

Richard P Steeds, Vandana Sagar, Shishir Shetty, Tessa Oelofse, Harjot Singh, Raheel Ahmad, Elizabeth Bradley, Rachel Moore, Suzanne Vickrage, Stacey Smith, Ivan Yim, Yasir S Elhassan, Hema Venkataraman, John Ayuk, Stephen Rooney, and Tahir Shah

Carcinoid heart disease (CHD) is a consequence of valvular fibrosis triggered by vasoactive substances released from neuroendocrine tumours, classically in those with metastatic disease and resulting in tricuspid and pulmonary valve failure. CHD affects one in five patients who have carcinoid syndrome (CS). Valve leaflets become thickened, retracted and immobile, resulting most often in regurgitation that causes right ventricular dilatation and ultimately, right heart failure. The development of CHD heralds a significantly worse prognosis than those patients with CS who do not develop valvular disease. Diagnosis requires a low threshold of suspicion in all patients with CS, since symptoms occur late in the disease process and clinical signs are difficult to elicit. As a result, routine screening is recommended using the biomarker, N-terminal pro-natriuretic peptide, and regular echocardiography is then required for diagnosis and follow-up. There is no direct medical therapy for CHD, but the focus of non-surgical care is to control CS symptoms, reduce tumour load and decrease hormone levels. Valve surgery improves long-term outcome for those with severe disease compared to medical management, although peri-operative mortality remains at between 10 and 20% in experienced centres. Therefore, care needs to be multidisciplinary at all stages, with clear discussion with the patient and between teams to ensure optimum outcome for these often-complex patients.