Myocardial Cell Signaling During the Transition to Heart Failure: Cellular Signaling and Therapeutic Approaches.

Cardiovascular disease leading to heart failure (HF) remains a leading cause of morbidity and mortality worldwide. Improved pharmacological and interventional coronary procedures have led to improved outcomes following acute myocardial infarction. This success has translated into an unforeseen increased incidence in HF. This review summarizes the signaling pathways implicated in the transition to HF following cardiac injury. In addition, we provide an update on cell death signaling and discuss recent advances in cardiac fibrosis as an independent event leading to HF. Finally, we discuss cell-based therapies and their possible use to avert the deteriorating nature of HF. © 2019 American Physiological Society. Compr Physiol 9:75-125, 2019.

A study of difference in serum 25-hydroxyvitamin D concentrations in patients with angiographically-defined coronary disease and healthy subjects.

BACKGROUND: Cardiovascular disease (CVD) is one of the most important causes of death in developing countries. The current study evaluates the serum 25-hydroxyvitamin D (25OHD), phosphate and calcium levels in patients with angiographically-defined coronary artery disease (CAD) and healthy subjects in a sample population in northeastern Iran. METHODS: There were 566 subjects aged between 20-80 years out of whom283 subjects with CAD were divided into two study groups based on their angiogram results; those with > 50% stenosis of one or more coronary arteries and those with ≤ 50% stenosis. Serum 25OHD levels and anthropometric parameters were measured for all subjects. RESULTS: There were approximately 53% (n = 303) males and 47% (n = 269) females in the population sample. We found that crude serum 25OHD concentrations were significantly higher in both the Angio- (21.6 ±â€¯11.8 ng/ml) and Angio+ (21.3 ±â€¯10.2 ng/ml) groups compared to the control subjects (16.4 ±â€¯9.5 ng/ml) (P < 0.001). CONCLUSION: The findings show that 25OHD state could be a risk factor for CAD, although this would need to be explored further, taking the potential confounding effects of diet into account in future studies.

Simvastatin Treatment Does Not Affect Serum Vitamin D Concentrations in Patients with Dyslipidemia: A Randomized Double-blind Placebo-controlled Cross-over Trial.

BACKGROUND: Hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) are antihyperlipidemic drugs with an established efficacy in stabilizing atherosclerotic plaques and preventing atherogenesis and reducing cardiovascular events. The purpose of this study was to determine the effect of simvastatin on serum Vitamin D status in dyslipidemic patients as Vitamin D status has an impact on monocyte/macrophage function and may also contribute to cardiovascular risk. METHODS: Selected individuals (n = 102) were treated with simvastatin (40 mg/day), or matching placebo in a randomized, double-blind, placebo-controlled, crossover trial. Each treatment period (with simvastatin or placebo) lasted for 30 days and was separated by a 2-week washout phase. Serum Vitamin D concentration was assessed pre- and post-treatment. RESULTS: Seventy-seven completed the trial, noncompliance with the study protocol and drug intolerance or relocation were the causes for drop-out. No significant carry-over effect was observed for the assessed parameters. There was a reduction in the serum levels of low-density lipoprotein cholesterol (P < 0.001), total cholesterol (P < 0.001), and triglycerides (P < 0.05). Nevertheless, simvastatin therapy did not significantly affect serum level of high-density lipoprotein cholesterol and Vitamin D level (P > 0.05). CONCLUSIONS: Short-term treatment with simvastatin (40 mg/day) does not have a significant affect on serum levels of Vitamin D.

Association between serum 25-hydroxyvitamin D concentrations and prevalence of metabolic syndrome.

PURPOSE: There is now good evidence that 25-hydroxyvitamin D (25OHD) status may have an important impact on the development and progression of cardiovascular disease. Because of the potential involvement of vitamin D deficiency in blood pressure control and immune responses, we aimed to investigate whether there was a relationship between 25OHD status and the prevalence of metabolic syndrome in an Iranian population. MATERIAL/METHODS: The study was carried out on a sample of 846 subjects [357(42.19%) males and 489(57.80%) females], derived from MASHAD STUDY. Serum 25OHD levels were measured using a competitive electroluminescence protein binding assay. Anthropometric indices were measured using standard protocols. RESULTS: Serum 25OHD was 12.7 (6.8-18.4) ng/ml in the metabolic syndrome (MetS) group and 14.1 (8.8-19.0) ng/ml in the group without metabolic syndrome (P=0.43). The frequency of vitamin D deficiency was 80.7% and 79.0% in subjects with or without metabolic syndrome in Iranian population. CONCLUSIONS: We found no significant difference in serum 25OHD concentrations between individuals with or without MetS and no significant linear relationship between serum 25OHD and several CVD risk factors.

Efficacy of different protocols of radioiodine therapy for treatment of toxic nodular goiter: systematic review and meta-analysis of the literature.

CONTEXT: To evaluate treatment success and hypothyroidism following main methods of radioiodine therapy of toxic nodular goiter (TNG); calculated versus fixed dose and high versus low dose of radioiodine. EVIDENCE ACQUISITIONS: We searched MEDLINE and SCOPUS databases from inception till July 2013, for clinical trials that compared two different methods of radioiodine administration in TNG. The trials were classified into two groups, those that compared fixed versus calculated dosimetry method and those that assessed high fixed dose versus low fixed dose method. Treatment response was defined as euthyroidism or hypothyroidism, one year after radioiodine administration. We calculated the risk ratio and risk difference of treatment response as well as permanent hypothyroidism as outcome variables. Random effects model was used for data pooling. RESULTS: The literature search yielded 2538 articles. Two randomized and five non-randomized clinical trials with 669 patients met the eligibility criteria for the meta-analysis. Patients with TNG who were treated according to the calculated method had 9.6% higher cure rate (risk ratio=1.17) and only 0.3% more permanent hypothyroidism compared to patients treated with the fixed dose method. There was no significant difference in the amount of administered radio-iodine in the two groups. Patients treated with fixed high dose had 18.1% more cure rate (risk ratio = 1.2) and 23.9% more permanent hypothyroidism (risk ratio = 2.40) compared to patients treated by fixed low dose protocols. CONCLUSIONS: Calculated radioiodine therapy may be preferred to fixed dose method in patients with TNG. High dose methods are associated with more response and more hypothyroidism.

Clinical value and severity of myocardial perfusion defects in asymptomatic diabetic patients with negative or weakly positive exercise treadmill test.

OBJECTIVE: Although coronary artery disease (CAD) is the leading cause of death in type 2 diabetic patients, it is frequently asymptomatic. Myocardial perfusion imaging (MPI) is reported to show ischemia in a significant number of asymptomatic diabetic patients. We studied the prevalence and severity of myocardial perfusion defects in asymptomatic diabetic patients and its clinical impact. METHODS AND PATIENTS: One hundred thirty consecutive asymptomatic patients, aged 35-65 years with type 2 diabetes mellitus and with no history of CAD and no cardiac symptoms were recruited in the study. Echocardiography, electrocardiography (ECG), routine laboratory tests and exercise treadmill test (ETT) were performed and patients with weakly positive or negative ETT underwent Dipyridamole MPI. Patients with positive ETT were referred to coronary angiography. Patients were followed for at least 17 months (mean 21.7 months) and any cardiac event was recorded. RESULTS: We studied 81 female and 49 male patients with mean age of 51.8 years. Negative, weakly positive and positive ETT result was noted in 74.3%, 15% and 10.7% respectively. 75% of patients with positive ETT had coronary artery disease in angiography. Gated myocardial perfusion SPECT was done in 106 patients. MPI showed reversible defect in 26.9% of the patients with a mean summed stress score of 3.3±1.8. Follow up completed in 112 patients and only one patient with abnormal MPI underwent coronary angiography followed by PTCA. No cardiac death, MI, UA or hospital admission occurred among our patients during follow up (17-26 months). Mean stress end diastolic volume (EDV) was significantly higher in patients with reversible defect compared to patients without reversible defect based on MPI findings (62.0±31.6 Vs 48.5±18.4 ml, P=0.04). Blood glucose and HbA1c were significantly higher in patients with ischemia compared to patients without ischemia (P<0.05). Meanwhile the ratio of TG to HDL was 6.06±3.2 in ischemic patients compared to 4.8±2.3 in normal subjects (P=0.03). CONCLUSION: Reversible defects are commonly seen in myocardial perfusion SPECT in asymptomatic diabetic patients and are mild in severity and not associated with adverse cardiac events. Routine approach for detection of CAD beginning with ETT seems to be appropriate in these patients.

Diabetic CVD--focus on vitamin D.

Cardiovascular disease (CVD) is the leading cause of mortality and morbidity among diabetics. Vitamin D deficiency is very common all over the world. Over last few years, vitamin D has been considered as an important regulating factor for cardiovascular health. Metabolic syndrome and obesity are highly prevalent in vitamin D deficient people. In fact all components of metabolic syndrome are affected by vitamin D. Vitamin D regulates insulin secretion and its action. It has also some controlling effect on Renin-Angiotensin system, which influences cardiomyocytes positively. Vitamin D plays a role in vascular system too. This vitamin reduces vascular calcification and inflammatory processes. Given the important role of Vitamin D in cardiovascular health, this review focuses on the impacts of vitamin D on the various CVD risk factors.

Unimaginable loss: contingent suicidal ideation in family members of oncology patients.

BACKGROUND: Family members of patients with cancer may reveal to the medical team that they are considering suicide after their loved one dies. No literature is available indicating how to assess risk and to intervene with these individuals. OBJECTIVE: The authors describe various alerting signs and seek to improve awareness and approaches to suicide prevention. METHOD: The authors present five cases of potential contingent suicide. RESULTS: Family members struggling with anticipatory grief challenge the clinical team at several points of decision-making. CONCLUSION: Close coordination among members of the patient's treatment team and psychiatric consultants is crucial for helping vulnerable family members move safely into adequately supported bereavement.