cholecalciferol and Myocardial-Infarction

Cohort studies have reported increased incidence of cardiovascular disease (CVD) among individuals with low vitamin D status. To date, randomized clinical trials of vitamin D supplementation have not found an effect, possibly because of using too low a dose of vitamin D.. To examine whether monthly high-dose vitamin D supplementation prevents CVD in the general population.. The Vitamin D Assessment Study is a randomized, double-blind, placebo-controlled trial that recruited participants mostly from family practices in Auckland, New Zealand, from April 5, 2011, through November 6, 2012, with follow-up until July 2015. Participants were community-resident adults aged 50 to 84 years. Of 47 905 adults invited from family practices and 163 from community groups, 5110 participants were randomized to receive vitamin D3 (n = 2558) or placebo (n = 2552). Two participants retracted consent, and all others (n = 5108) were included in the primary analysis.. Oral vitamin D3 in an initial dose of 200 000 IU, followed a month later by monthly doses of 100 000 IU, or placebo for a median of 3.3 years (range, 2.5-4.2 years).. The primary outcome was the number of participants with incident CVD and death, including a prespecified subgroup analysis in participants with vitamin D deficiency (baseline deseasonalized 25-hydroxyvitamin D [25(OH)D] levels <20 ng/mL). Secondary outcomes were myocardial infarction, angina, heart failure, hypertension, arrhythmias, arteriosclerosis, stroke, and venous thrombosis.. Of the 5108 participants included in the analysis, the mean (SD) age was 65.9 (8.3) years, 2969 (58.1%) were male, and 4253 (83.3%) were of European or other ethnicity, with the remainder being Polynesian or South Asian. Mean (SD) baseline deseasonalized 25(OH)D concentration was 26.5 (9.0) ng/mL, with 1270 participants (24.9%) being vitamin D deficient. In a random sample of 438 participants, the mean follow-up 25(OH)D level was greater than 20 ng/mL higher in the vitamin D group than in the placebo group. The primary outcome of CVD occurred in 303 participants (11.8%) in the vitamin D group and 293 participants (11.5%) in the placebo group, yielding an adjusted hazard ratio of 1.02 (95% CI, 0.87-1.20). Similar results were seen for participants with baseline vitamin D deficiency and for secondary outcomes.. Monthly high-dose vitamin D supplementation does not prevent CVD. This result does not support the use of monthly vitamin D supplementation for this purpose. The effects of daily or weekly dosing require further study.. clinicaltrials.gov Identifier: ACTRN12611000402943.

Topics: Aged; Aged, 80 and over; Angina Pectoris; Arrhythmias, Cardiac; Arteriosclerosis; Cardiovascular Diseases; Cholecalciferol; Dietary Supplements; Double-Blind Method; Female; Heart Failure; Humans; Hypertension; Male; Middle Aged; Myocardial Infarction; New Zealand; Proportional Hazards Models; Stroke; Venous Thrombosis; Vitamin D Deficiency; Vitamins

Vitamin D deficiency is associated with acute myocardial infarction (AMI); thus we aimed to explore improvement effects of 1,25-dihydroxyvitamin D3 (VD3) on the AMI and its potential mechanism. AMI models were constructed using male C57/BL6J mice and randomly treated with normal saline or VD3, using sham rats as control. Heart functions, myocardial damage, apoptosis, and inflammation were evaluated. Cardiomyocytes isolated from 3-day-old suckling mice were used for in vitro verification. After VD3 treatment, AMI-induced cardiac dysfunction was reversed with better cardiac function parameters. VD3 treatment reduced inflammatory cell infiltration and myocardial infarction area accompanied by the reduction of inflammatory factors and myocardial infarction markers compared with the AMI group. VD3 treatment obviously alleviated AMI-induced myocardial apoptosis, along with Bcl-2 upregulation and downregulation of caspase-3, caspase-9, and Bax. Both in vivo and in vitro experiments revealed that VD3 enhanced the expression of LC3II and Beclin-1 and decreased soluble p62. Furthermore, VD3 enhanced the AMI-caused inhibition of PI3K, p-AKT, and p-mTOR expression, which was conversely reversed by the addition of 3-methyladenine in vitro. The study highlights the improvement effects of VD3 on cardiac functions. We proposed a potential mechanism that VD3 protects against myocardial damage, inflammation, and apoptosis by promoting autophagy through PI3K/AKT/mTOR pathway.

Topics: Animals; Autophagy; Cells, Cultured; Cholecalciferol; Male; Mice; Mice, Inbred C57BL; Myocardial Infarction; Myocytes, Cardiac; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Rats; TOR Serine-Threonine Kinases; Vitamin D Deficiency

The vitamin D(3) and nicotine (VDN) model is a model of isolated systolic hypertension (ISH) due to arterial calcification raising arterial stiffness and vascular impedance similar to an aged and stiffened arterial tree. We therefore analyzed the impact of this aging model on normal and diseased hearts with myocardial infarction (MI). Wistar rats were treated with VDN (n = 9), subjected to MI by coronary ligation (n = 10), or subjected to a combination of both MI and VDN treatment (VDN/MI, n = 14). A sham-treated group served as control (Ctrl, n = 10). Transthoracic echocardiography was performed every 2 wk, whereas invasive indexes were obtained at week 8 before death. Calcium, collagen, and protein contents were measured in the heart and the aorta. Systolic blood pressure, pulse pressure, thoracic aortic calcium, and end-systolic elastance as an index of myocardial contractility were highest in the aging model group compared with MI and Ctrl groups (P(VDN) < 0.05, 2-way ANOVA). Left ventricular wall stress and brain natriuretic peptide (P(VDNxMI) = not significant) were highest, while ejection fraction, stroke volume, and cardiac output were lowest in the combined group versus all other groups (P(VDNxMI) < 0.05). The combination of ISH due to this aging model and MI demonstrates significant alterations in cardiac function. This model mimics several clinical phenomena of cardiovascular aging and may thus serve to further study novel therapies.

Topics: Aging; Animals; Cardiomyopathies; Cardiovascular System; Cholecalciferol; Disease Models, Animal; Hypertension; Male; Myocardial Contraction; Myocardial Infarction; Nicotine; Rats; Rats, Wistar; Stroke Volume; Ventricular Dysfunction, Left

We previously found that a pulse dose of vitamin D3 increased [99mTc]PPi uptake by rat myocardial necrosis. Vitamin D3 raised serum and lesion [Ca] but not, we now report, lesion [Fe]. We now also report that D3 increased [99Tc]PPi uptake by myocardial infarcts (L) in dogs from 0.345 +/- 0.007% administered (kg) dose/g in controls to 0.703 +/- 0.089 in treated (p less than 0.025). Vitamin D3 decreased uptake by dog bone (B) as measured in rib and sternum, increasing L/B from 1.10 +/- 0.23 to 2.30 +/- 0.52 (p = 0.06) X (L) was positively, (p less than 0.005) and uptake by sternum was negatively (p less than 0.05) correlated with serum [Ca] and [P], respectively. Scintigrams graded by a "blinded" observer, showed 4+, 4+, and 3+ infarcts, respectively, in three D3-treated dogs, and 2+, 2+, and 1+, respectively, in three untreated. One untreated and one treated dog were negative; the latter showed the least response to D3 in serum [Ca] and [99mTc] in tissue samples. Vitamin D3 can increase L/B in dogs, enhancing scintigraphic images.

Topics: Animals; Bone and Bones; Calcium; Cholecalciferol; Diphosphates; Dogs; Iron; Myocardial Infarction; Phosphorus; Radionuclide Imaging; Rats; Rats, Inbred Strains; Technetium; Technetium Tc 99m Pyrophosphate