Non-linear associations of 25-hydroxyvitamin D concentrations with risk of cardiovascular disease and all-cause mortality: Results from The Health Improvement Network (THIN) database.

BACKGROUND: There is increasing evidence that vitamin D supplementation may only be beneficial in people with vitamin D deficiency, and the lack of sufficient people with very low vitamin D levels could explain the lack of protection against cardiovascular disease (CVD) reported in recent clinical trials of vitamin D supplementation. The aim of this study was to assess associations of low to moderate circulating concentrations of 25-hydroxyvitamin D (25(OH)D with risk of incident CVD and all-cause mortality, as well as the risk of ischaemic heart disease (IHD), cerebrovascular disease, and heart failure separately. METHODS AND RESULTS: Longitudinal analysis of electronic health records in The Health Improvement Network (THIN), a UK primary care database. The analysis included 180,263 patients age 18 years and older without a history of CVD and with circulating concentrations of 25(OH)D. After a mean follow-up of 2.2 (SD 1.7) years, there were 3747 patients diagnosed with CVD and 3912 patients died. Compared to patients in the highest quintile of 25(OHD) (≥ 67.5 nmol/L), those in the lowest 25(OH)D quintile (<23.1 nmol/L) had a hazard ratio (HR) of 1.24 (95% CI 1.12-1.38, P <  0.001) for CVD and 1.71 (1.55-1.88, P <  0.001) for mortality. The HR for both outcomes associated with 25(OH)D concentration was non-linear, being significantly increased in patients with 25(OH)D <35 nmol/L, and highest in those with 25(OH)D <25 nmol/L, although increased for mortality at 25(OH)D ≥100 nmol/L. The increased CVD HR in the lowest 25(OH)D quintile was more from IHD (1.35, 95% CI 1.13-1.60) and heart failure (1.38, 95% CI 1.08-1.77), than from cerebrovascular disease (1.13, 95% CI 0.97-1.31). CONCLUSION: Low 25(OH)D are associated with highest risk of CVD and mortality, and are consistent with accumulating evidence that increased risk of these diseases occurs primarily in people with vitamin D deficiency.

The effects of dietary intervention on HIV dyslipidaemia: a systematic review and meta-analysis.

BACKGROUND: Efficacy of dietary intervention for treatment and prevention of HIV-related lipid disturbances has not been well established. METHODS: We conducted a systematic search of electronic databases supplemented with manual searches and conference abstracts, without language restriction. All randomised controlled trials (RCTs) with blood lipid outcomes, involving dietary intervention or supplementation for the treatment or prevention of adult HIV dyslipidaemia, versus no or other intervention were included. Two authors using predefined data fields, including study quality indicators, extracted data independently. RESULTS: Eighteen studies (n = 873) met our inclusion criteria. Seven RCTs for omega-3 supplementation (n = 372), and four RCTs for dietary intervention (n = 201) were meta-analysed using random-effects models. Mild statistical heterogeneity was observed. Dietary intervention reduced triglyceride levels by -0·46 mmol/l (95%CI: -0·85 to -0·07 mmol/l) compared to control. Omega-3 supplementation reduced triglyceride levels by -1.12 mmol/l, (95%CI: -1·57 to -0·67 mmol/l) and total cholesterol, -0·36 mmol/l (95%CI: -0·67 to -0·05 mmol/l) compared to placebo/control. CONCLUSIONS: Both omega-3 supplementation and dietary intervention reduced triglyceride level, with the latter possibly to a smaller extent. While dietary interventions are beneficial, more stringent dietary approaches may be necessary to fully address lipid disturbances in HIV patients. TRIAL REGISTRATION: PROSPERO 2011:CRD42011001329.

Vitamin D levels predict all-cause and cardiovascular disease mortality in subjects with the metabolic syndrome: the Ludwigshafen Risk and Cardiovascular Health (LURIC) Study.

OBJECTIVE: Optimal vitamin D levels are associated with reduced cardiovascular and all-cause mortality. We investigated whether optimal 25-hydroxyvitamin D (25[OH]D) is protective in individuals with the metabolic syndrome. RESEARCH DESIGN AND METHODS: The Ludwigshafen Risk and Cardiovascular Health (LURIC) study is a cohort study of subjects referred for coronary angiography between 1997 and 2000, from which 1,801 with the metabolic syndrome were investigated. Mortality was tracked for a median of 7.7 years. Multivariable survival analysis was used to estimate the association between 25(OH)D levels and mortality. RESULTS: Most subjects (92%) had suboptimal levels of 25(OH)D (<75 nmol/L), with 22.2% being severely deficient (<25 nmol/L). During follow-up, 462 deaths were recorded, 267 (57.8%) of which were cardiovascular in origin. After full adjustment, including the metabolic syndrome components, those with optimal 25(OH)D levels showed a substantial reduction in all-cause (hazard ratio [HR] 0.25 [95% CI 0.13-0.46]) and cardiovascular disease mortality (0.33 [0.16-0.66]) compared with those with severe vitamin D deficiency. For specific cardiovascular disease mortality, there was a strong reduction for sudden death (0.15 [0.04-0.63]) and congestive heart failure (0.24 [0.06-1.04]), but not for myocardial infarction. The reduction in mortality was dose-dependent for each of these causes. CONCLUSIONS: Optimal 25(OH)D levels substantially lowered all-cause and cardiovascular disease mortality in subjects with the metabolic syndrome. These observations call for interventional studies that test whether vitamin D supplementation provides a useful adjunct in reducing mortality in these subjects.

Hyperglycaemia and vitamin D: a systematic overview.

Vitamin D plays a role in a range of functions that may impact on glycaemic control. In this study we systematically report on clinical studies evaluating the impact of vitamin D on aspects of hyperglycaemia in non-pregnant adults. A total of 1,294 articles, of which 417 were reviews, were identified. No well-designed randomised, controlled trials were identified that specifically investigated the effects of vitamin D supplementation on glucose and insulin concentrations. The majority of the studies that are available were poorly designed, having limited numbers, short study duration, or were conducted in volunteers with normal baseline, as measured by 25-hydroxyvitamin D (25(OH)D), concentrations or used inadequate doses of the supplements to normalise vitamin D concentrations, or used inappropriate analyses. Most studies did not observe improvements in glycaemia, with few exceptions. The results were more equivocal for aspects of insulin resistance. Most found no benefit on measures of insulin resistance, although some did. However, more studies described improved insulin release, although data from the studies to date are really inadequate to provide any reliable conclusions. Well-conducted randomised, controlled trials with adequate vitamin D doses are required to effectively assess whether this vitamin can reduce the incidence of diabetes.

Fish consumption and mortality in Hong Kong Chinese--the LIMOR study.

PURPOSE: To investigate the association between fish consumption and mortality in 36,003 Chinese. METHODS: A case-control study collected 81% of all deaths of those aged 30+ from all four Hong Kong death registries in 1998. Relatives registering the deaths provided demographic, dietary and other lifestyle data for the deceased (case) and a similarly aged living person (control). Causes of death were provided by the Department of Health. Logistic regression was used to calculate the mortality odds ratios (ORs) for fish consumption adjusting for potential confounders in the 23,608 cases and 12,395 controls. RESULTS: Compared with the lowest fish consumption of less than or equal to three times a month, higher consumption of one to three times a week was associated with lower mortality ORs (95% confidence interval [CI]) of 0.75 (0.62-0.89) for all-cause, 0.66 (0.48-0.92) for ischemic heart disease (IHD), 0.70 (0.50-0.98) for stroke, 0.66 (0.53-0.82) for cancer, but not for injury and poisoning. The highest level of fish consumption of greater than or equal to four times a week also reduced mortality with ORs (95% CI) of 0.80 (0.68-0.94) for all-cause and 0.63 (0.47-0.85) for IHD. CONCLUSIONS: Fish consumption significantly reduced mortality from several causes in this sample. Further longitudinal studies to confirm the association are needed.

Rimonabant for the treatment of obesity.

Obesity is a growing public health problem that is already reaching epidemic proportions and is increasingly encompassing young children and adolescents. Despite the increasing prevalence and the health risks associated with obesity, the pharmacotherapeutic options for treating obesity are limited. The endogenous cannabinoid or endocan-nabinoid system (ECS) was discovered in the early 1990s in relation to work on the action of components of marijuana. Central activation of the ECS promotes food ingestion. The endogenous cannabinoids exert their pharmacologic action through interaction with the specific receptors, CB(1) and CB(2). CB(1) receptors are located predominantly in the brain and peripherally in adipose tissue, liver, skeletal muscle and the gastrointestinal tract. In July 2006, European regulatory authorities approved the use of rimonabant, SR141716, a selective CB1 receptor antagonist, in obese patients (BMI > or =30kg/m(2), or >27kg/m(2) with complications). However, in June 2007, despite extensive clinical trial data, the FDA's Endocrine and Metabolic Drugs Advisory Committee (EMDAC) concluded that the safety of rimonabant had not been adequately demonstrated by the manufacturer Sanofi-Aventis; the full application was subsequently withdrawn. This review article provides evidence and outlines some patents for the use of rimonabant and potential safety concerns which still prevent its use in the single largest market for drugs of its kind.

Diet synergies and mortality--a population-based case-control study of 32,462 Hong Kong Chinese older adults.

BACKGROUND: Food and drink are not consumed in isolation and can have complimentary effects enhancing or blocking the overall uptake of nutrients. We investigated how combinations of foods, drinks, and smoking affected mortality. Method Adjusted logistic regression was used to assess the joint effect of healthy foods, less healthy foods, smoking, and alcohol use on mortality in a case-control study of all Chinese adults aged 60 or over who died in 1998; 21,494 dead cases (81% of all registered deaths) and 10,968 live controls were included. RESULTS: There was a significant trend of increasing all-cause mortality risk with decreasing healthy food consumption (P < 0.001), and the increase in risk was significantly steeper for people with high intakes of less healthy food (P for interaction <0.001). There was a steeper risk from increasing less healthy food intake in ever-smokers and people not drinking tea regularly (P < 0.001), while the J-shaped relationship between alcohol and mortality differed in shape with level of less healthy food intake. CONCLUSION: Intake of some dietary items may modify the effect of others. An analysis framework explicitly recognizing complementary and potentially synergistic effects of food, drinks, and smoking could enhance our understanding of dietary epidemiology.

Effects of Tai Chi and resistance training on cardiovascular risk factors in elderly Chinese subjects: a 12-month longitudinal, randomized, controlled intervention study.

BACKGROUND: Tai Chi is rapidly gaining in popularity, worldwide. This study was performed to assess its impact on cardiovascular risk factors in comparison with resistance training exercises in elderly Chinese subjects. METHODS: A total of 207 healthy elderly participants (65-74 years, 113/207 (55%) men) were randomly assigned to one of three intervention groups: (1) Tai Chi, three times/week for 1 h/session (n = 64); (2) resistance training exercise, three times/week for 1 h/session (n = 65); (3) usual level of physical activity control group (n = 78). Anthropometric measures, dual X-ray densitometry body composition, blood pressure, lipids, glycaemic and insulin sensitivity indices were measured at baseline and 12 months. Repeated-measures analysis of variance (anova) was used to assess the between-group changes using a last-observation-carried-forward intention-to-treat approach. RESULTS: A total of 180 (87.0%) subjects completed the study. No significant changes were identified in the Tai Chi group compared to the resistance training or control group. Of the primary outcomes, only the improvement in the insulin sensitivity index differed, being significantly greater in the resistance training than in the control group [mean difference 0.018 (95% confidence interval ( CI) 0.000-0.037) mmol glucose/min, P = 0.02), and tending to be greater than in the Tai Chi group (mean difference 0.019 (95% CI 0.000-0.038) mmol glucose/min, P < 0.06). CONCLUSION: Tai Chi had no significant effect on any measure compared to the controls, whereas resistance training improved the insulin sensitivity index in this 12-month study.

Effects of vitamins C and E on oxidative stress markers and endothelial function in patients with systemic lupus erythematosus: a double blind, placebo controlled pilot study.

OBJECTIVE: Patients with systemic lupus erythematosus (SLE) experience excess morbidity and mortality due to coronary artery disease (CAD) that cannot be fully explained by the classical CAD risk factors. Among emerging CAD risk factors, oxidative stress is currently being emphasized. We evaluated the effects of longterm antioxidant vitamins on markers of oxidative stress and antioxidant defense and endothelial function in 39 patients with SLE. METHODS: Patients were randomized to receive either placebo or vitamins (500 mg vitamin C and 800 IU vitamin E daily) for 12 weeks. Markers of oxidative stress included malondialdehyde (MDA) and allantoin. Antioxidants measured included erythrocyte superoxide dismutase and glutathione peroxidase, plasma total antioxidant power (as FRAP value), and ascorbic acid and vitamin E concentrations. Endothelial function was assessed by flow-mediated dilatation (FMD) of the brachial artery and plasma concentration of von Willebrand factor (vWF) and plasminogen activator inhibitor type 1 (PAI-1). Primary outcome of the study included the change in lipid peroxidation as revealed by MDA levels. Secondary outcomes included changes in allantoin and antioxidant levels and change in endothelial function. RESULTS: After treatment, plasma ascorbic acid and alpha-tocopherol concentrations were significantly (p < 0.05) increased only in the vitamin-treated group, associated with a significant decrease (p < 0.05) in plasma MDA. Other oxidative stress markers and antioxidant levels remained unchanged in both groups. FMD and vWF and PAI-1 levels remained unchanged in both groups. CONCLUSION: Combined administration of vitamins C and E was associated with decreased lipid peroxidation, but did not affect endothelial function in patients with SLE after 3 months of therapy.

Antihypertensive effects of tannins isolated from traditional Chinese herbs as non-specific inhibitors of angiontensin converting enzyme.

The tannins are natural polyphenols, able to precipitate water-soluble alkaloids and possess an inhibitory action on the angiotensin converting enzyme (ACE). We identified 18 polyphenolic compounds (tannins) from Chinese herbs and examined the in vitro effects of these tannins on ACE activity, including determination of the 50% inhibitory concentrations (IC50), specificity and mode of inhibition. We also assessed the in vivo inhibitory effect of the tannins on angiotensin I-induced blood pressure elevation in spontaneously hypertensive rats (SHR). Nine tannins with an IC50 <200 microM for ACE inhibitors were identified belonging to three tannin classes: caffeoylquinates, flavan-3-ols and gallotannins. In vitro, we found caffeoylquinates chelate the ACE zinc cofactor. Two of the flavan-3-ols: epigallocatechin-3-O-gallate and epigallocatechin-3-O-methylgallate, and one of gallotannin: 1, 2, 3, 4, 6-penta-O-galloyl-beta-D-glucose were non-specific inhibitors because also reduced the activity of trypsin and chymotrypsin. The ACE inhibition of 1, 2, 3, 4, 6-penta-O-galloyl-beta-D-glucose was also reduced after addition of bovine serum albumin, suggesting a non-specific mode of action. In vivo, 1,2,3,6-tetra-O-galloyl-beta-D-glucose and epigallocatechin-3-O-methylgallate had a strong dose-dependent hypotensive effect reducing the blood pressure significantly in the SHR with infusion of the angiotensin I. These findings indicate that some of the tannins isolated from herbs inhibit ACE activity non-specifically. The ACE inhibitory effect of these tannins may explain the hypotensive effects of some traditional Chinese herbs.

Protective effects of trilinolein extracted from panax notoginseng against cardiovascular disease.

Trilinolein is a triacylglycerol purified from a commonly used traditional Chinese medicine Panax notoginseng. Trilinolein has been reported to provide a number of beneficial effects including reducing thrombogenicity and arrhythmias and increasing erythrocyte deformability. Additionally, trilinolein has been reported to be an antioxidant, which can counteract free radical damage associated with atherogenesis, and myocardial damage seen with ischaemia and reperfusion. These pharmacologic effects may explain the perceived benefits derived from treating circulatory disorders with the herb over the centuries.