Vitamin D supplementation and major cardiovascular events: D-Health randomised controlled trial
1. In this randomized controlled trial, it was found that vitamin D supplementation may be associated with a decreased risk of major cardiovascular events, though the absolute difference identified was small and the confidence interval was consistent with a null finding.Â
Evidence Rating: 1 (Excellent)Â
Two of the leading causes of death globally include coronary artery disease and stroke, and investigating potential protective factors is relevant to reducing morality. There is evidence that Vitamin D receptor is expressed in cells throughout the vascular system, and that the active form of vitamin D, calcitriol, exerts regulatory effects on inflammation, the renin-angiotensin-aldosterone system, and vascular smooth muscle. Data from the D-Health Trial was analyzed to determine whether monthly vitamin D supplementation impacted the incidence of major cardiovascular events in Australian adults over 60 years of age. A total of 21315 participants were randomized 1:1 to either a placebo group or a Vitamin D group, where the latter group would be receiving large intermittent doses of 60000 IU monthly. At follow up, there were 1336 major cardiovascular events (vitamin D group n=637 (6.0%); placebo n=699 (6.6%). At five years post-randomization, the number needed to treat (NNT) to avoid one major cardiovascular event was 172. While there was evidence that supplementation with 60000 IU of vitamin D3 per month for up to 5 years reduced the incidence of major cardiovascular events, particularly myocardial infarction (HRÂ 0.81; 95% CI [0.67 to 0.98]) and coronary revascularization (HRÂ 0.89; 95% CI [0.78 to 1.01]), the absolute differences were small. For all major cardiovascular events (MACEs), there was some evidence that statin use and other cardiovascular drugs used at baseline could strengthen the effects of vitamin D supplementation in the study.Â
1. In a single-center prospective cohort study, sodium-glucose cotransporter-2 (SGLT2) inhibitor administration was found to reduce the risk of statin-induced abnormal blood glucose levels in patients with heart failure with reduced ejection fraction who had previously underwent percutaneous cardiac intervention.Â
Evidence Rating: 1 (Excellent)
Coronary artery disease is a common cause of heart failure and a major contributor to mortality worldwide, and statins are a cornerstone of treatment and prevention for cardiovascular events. There is evidence that supports an increased risk for new-onset diabetes mellitus (DM) and decreased insulin sensitivity with the long-term use of statin therapies. Thus, the current study sought to investigate whether the administration of a sodium-glucose cotransporter-2 (SGLT2) inhibitor could reduce insulin resistance in the setting of those taking a statin with heart failure with reduced ejection fractions (HFrEF). Of the 333 non-diabetic patients with HFrEF who underwent percutaneous cardiac intervention (PCI), 198 were assigned to a matched group, and 135 were assigned so a SGLT2 inhibitor group. At follow-up (mean follow up of 13 months), those in the SGLT2 inhibitor group were significantly less likely to develop statin-induced abnormal blood glucose levels (6.06% in the matched group versus 0.74% in the SGLT2i group, P < 0.05). While these results are promising, potential differences between participants’ diets were not taken into account, and individual islet cell function was not measured. Family history of Type 2 DM was also not accounted for in these results. Overall, though, these results could point to a protective role of SGLT2 inhibitors in the context of HFrEF being treated with statins.Â
1. In this single-centre prospective cohort study, development of a Swedish Palliative Care Guide to improve integrated geriatric and palliative care medicine was found to significantly improve patient satisfaction with care although no differences were found in other outcomes such as health-related quality or symptom burden.Â
Evidence Rating: 1 (Excellent)Â
The overall proportion of older adults in the world population continues to increase, and with this comes more individuals affected by multimorbidity, cognitive decline, and frailty. The integration of geriatric medicine and palliative medicine (coined as geriatric palliative care) has been proposed as a way to increase patient-centredness of care, decrease symptom burdens, and increase informed decision-making. The Swedish Palliative Care Guide (S-PCG) was designed to provide interprofesional guidance for evidence-based and patient-centred palliative care, independent of diagnosis, healthcare setting, and remaining lifespan. The current study aimed to evaluate the effect of using the S-PCG on patient satisfaction, health-related quality of life, symptom burden, ad next-of-kin satisfaction. This study was divided into three phases. First, the pre-intervntion phase where patient care was assessed without the S-PCG framework. Second, teaching the staff and clinical implementation of S-PCG. Third, the intervention phase, where patients were consecutively included as S-PCG was in clinical use. Adults above the age of 65 without evidence of cognitive impairment or a COVID-19 diagnosis were included if they were in hospital for five or more days during either the pre-intervention or intervention periods. In 9 of 10 questions measuring satisfaction with care, results were significantly better in the intervention group (Ps < 0.001 to 0.023). Next of kin also rates their satisfaction with the hospitalization significantly better after the intervention was implemented (P < 0.01). Discharge quality was largely unchanged. No significant differences were noted for health-related quality or symptom burden pre- and post-intervention. These effects were seen after a short hospital stay and lasted several weeks after discharge. While the study was strong in that it had many participants with a high response rate, one limitation is the fact that hospital stays were relatively short, limiting the potential benefits on symptom burden.Â
1. In a Swedish cohort, lower cardiorespiratory fitness (CRF) as measured by maximal oxygen consumption (Vo2max) was found to be associated with a greater incidence of colon, lung, and prostate cancer in a 9.6 year period.
2. In patients diagnosed with cancer, greater CRF was additionally found to be associated with lower mortality risk, though the strength of this correlation was affected by factors such as underlying cancer diagnosis and demographic factors.
Evidence Rating: 2 (Good)Â
Although cardiorespiratory fitness (CRF) levels is a recognized and important risk factor for cancer incidence and death, the true quantitative effects are often poorly generalized. Using maximal oxygen consumption (Vo2max) as millimeters per minute per kilogram) as a measure for CRF, data retrieved from the health profile assessment database for 177,709 Swedish men (age range, 18-75 years; mean [SD] age, 42 [11] years; mean [SD] body mass index, 26 [3.8]) were analyzed to further address this gap in literature. CRF was stratified as a continuous variable into 4 groups (very low (≤25 mL/min/kg), low (>25-35 mL/min/kg), moderate (>35-45 mL/min/kg), and high CRF (>45 mL/min/kg)). At a mean follow-up of 9.6 years, 2700 cases of either colon, lung, or prostate cancer had occurred, and of those cases, 500 had resulted in death. Patients who had developed cancer in this time period had a lower mean estimated Vo2max than those without cancer (P < .001 for colon cancer, P = .01 for lung cancer, and P < .001 for prostate cancer). Patients who died of cancers also had a lower mean CRF. Higher estimated Vo2max was associated with significantly lower risk of colon and lung cancer incidence, but with increased risk for prostate cancer incidence. There was a significant association between higher Vo2max and decreased risk for colon, lung, and prostate cancer-related deaths. When adjusting for lifestyle habits, colon cancer incidence and prostate cancer mortality remained significantly reduced in those with moderate or high CRF. For lung cancer, there was significantly decreased incidence and mortality for low, medium, and high CRF groups compared to the very low CRF group. Age did modify the associations, with decreased risk with higher CRF for lung cancer incidence and death evident only in men ≥ 60 years. Overall, although this study presents some promising evidence for CRF as a potential protective factor against certain cancers, limitations include a potentially homogenous population (voluntary participation and inclusion of only those who are employed) and lack of generalizability to other types of cancers.Â
1. In this prospective cohort study, it was found that the lateral ventricles, front and temporal lobes, and anterior and inferior white matter regions exhibited the greatest age dependency on volume change, though all structures examined appeared to accelerate in volume loss with age,Â
Evidence Rating: 1 (Excellent)
The literature indicates that many neurodegenerative diseases begin to take place decades prior to symptom onset. Gathering a better understanding of the longitudinal patterns of change in different regions of the brain could provide insights into these early processes. This is the first large-scale longitudinal study that harnesses magnetic resonance imaging (MRI) of the brain in individuals without dementia as a means to quantify aging-related changes in brain volume. A total of 653 participants (mean [SD] age at baseline, 55.1 [9.3] years; median age, 55 years [IQR, 47-62 years]; 447 men [69%]) from a Japanese comprehensive screening program participated in more than 10-year serial visits. Each brain structure showed individual levels of age-dependent volume change, and an annual decrease of 0.4% of whole-brain volume was observed. In particular, a marked volume decrease in the parenchyma and an increase in CSF space (ventricles and sulci) were observed (ventricle regression coefficient, 0.042 [95% CI, 0.037-0.047]; P < .001; sulcus regression coefficient, 0.021 [95% CI, 0.018-0.023]; P < .001). Specifically, the lateral ventricle exhibited the largest changes in growth from year to year. The frontal and temporal lobes showed a larger age dependency than the parietal and occipital lobes, and white matter regions in the anterior and inferior portions of the brain showed greater age dependency than the posterior white matter. Cerebellar volume loss accelerated linearly with age. Cerebral cortex volume loss was gradual, at 0.4% across all decades of life. The hippocampus and temporal lobe both demonstrated rapidly accelerating volume decreases with increasing age, but the hippocampus was more preserved in the earlier stages of life. While this study is the largest of its kind to date and uses longitudinal imaging data to inform its results, there is no way to quantify whether participants were already in the pre-clinical Alzheimer’s disease stages when entering the study. The homogeneity of this population also prevents generalizability. However, overall, characterizing the normal distributions of brain volume and atrophy rates in a cognitively healthy population could potentially allow the medical community to risk-stratify high-risk subgroups and facilitate stratification of high-risk subgroups.
Image: PD
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