Cardiovascular Events In People Research Articles

Novel approaches to the treatment of hyperglycaemia in type 2 diabetes mellitus.

Control of hyperglycaemia is a fundamental therapeutic goal in patients with type 2 diabetes. The progressive nature of β-cell dysfunction in type 2 diabetes leads to the need for escalating anti-hyperglycaemic treatment, including insulin, in most patients. Given the prevalence of complications such as weight gain and hypoglycaemia associated with traditional anti-hyperglycaemic agents (AHA), including sulphonylureas and insulin, it is unsurprising that recent years have seen the development of novel agents to treat hyperglycaemia. With increasing evidence supporting the need for a multi-faceted approach to the prevention of adverse cardiovascular events in people with type 2 diabetes, a patient-centred and individualised management strategy addressing lifestyle, cardiovascular risk factor modification and glycaemic control remains critical in improving outcomes in these patients.

Both vascular endothelial growth factor and soluble Flt-1 are increased in type 2 diabetes but not in impaired fasting glucose.

Inadequate vascular remodeling is contributory to increased cardiovascular events in people with type 2 diabetes mellitus (DM) and impaired fasting glucose (IFG). Vascular endothelial growth factor (VEGF) and its regulatory molecule soluble Flt-1(sFlt-1) play important roles in atherogenesis. We measured fasting plasma concentrations of VEGF and sFlt-1 in 11 nondiabetic (ND) (aged 46.1 +/- 2.1 years; body mass index [BMI], 26.1 +/- 0.9 kg/m; glucose, 5.0 +/- 0.1 mM), 15 IFG (aged 52.9 +/- 1.8 years; BMI, 32.7 +/- 1.3 kg/m; glucose, 6.4 +/- 0.1 mM), and 8 DM (aged 55.8 +/- 3.2 years; BMI, 30.0 +/- 1.0 kg/m; glucose, 9.3 +/- 0.5 mM) subjects. Plasma VEGF (42.1 +/- 4.0 vs 24.2 +/- 0.9 vs 29.4 +/- 3.8 pg/mL, respectively) and sFlt-1 (119.4 +/- 4.9 vs 58.9 +/- 3.2 vs 56.7 +/- 1.2 pg/mL, respectively) concentrations were higher (P < 0.04) in DM than IFG and ND subjects. Whereas VEGF concentrations were significantly lower (P < 0.05) in IFG than in ND subjects, sFlt-1 concentrations did not differ between the IFG and ND subjects. Although plasma VEGF concentrations were higher (35%) in DM than in ND subjects, VEGF action on vascular remodeling was likely attenuated by higher sFlt-1 concentrations in DM. In contrast, IFG subjects did not have major perturbations in either VEGF or sFlt-1 levels. Further studies defining the roles of these mediators in DM and IFG are necessary to extend these observations.

Low alanine aminotransferase levels and higher number of cardiovascular events in people with Type 2 diabetes: analysis of the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study.

To determine whether alanine aminotransferase or gamma-glutamyltransferase levels, as markers of liver health and non-alcoholic fatty liver disease, might predict cardiovascular events in people with Type 2 diabetes. Data from the Fenofibrate Intervention and Event Lowering in Diabetes study were analysed to examine the relationship between liver enzymes and incident cardiovascular events (non-fatal myocardial infarction, stroke, coronary and other cardiovascular death, coronary or carotid revascularization) over 5 years. Alanine aminotransferase measure had a linear inverse relationship with the first cardiovascular event occurring in participants during the study period. After adjustment, for every 1 sd higher baseline alanine aminotransferase measure (13.2 U/l), the risk of a cardiovascular event was 7% lower (95% CI 4-13; P = 0.02). Participants with alanine aminotransferase levels below and above the reference range 8-41 U/l for women and 9-59 U/l for men, had hazard ratios for a cardiovascular event of 1.86 (95% CI 1.12-3.09) and 0.65 (95% CI 0.49-0.87), respectively (P = 0.001). No relationship was found for gamma-glutamyltransferase. The data may indicate that in people with Type 2 diabetes, which is associated with higher alanine aminotransferase levels because of prevalent non-alcoholic fatty liver disease, a low alanine aminotransferase level is a marker of hepatic or systemic frailty rather than health.

The influence of inhaled multi-walled carbon nanotubes on the autonomic nervous system.

BackgroundHeart rate and cardiovascular function are regulated by the autonomic nervous system. Heart rate variability (HRV) as a marker reflects the activity of autonomic nervous system. The prognostic significance of HRV in cardiovascular disease has been reported in clinical and epidemiological studies. The present study focused on the influence of inhaled multi-walled carbon nanotubes (MWCNTs) on autonomic nervous system by HRV analysis.MethodsMale Sprague–Dawley rats were pre-implanted with a telemetry device and kept in the individual cages for recovery. At week four after device implantation, rats were exposed to MWCNTs for 5 h at a concentration of 5 mg/m3. The real-time EKGs were recorded by a telemetry system at pre-exposure, during exposure, 1 day and 7 days post-exposure. HRV was measured by root mean square of successive differences (RMSSD); the standard deviation of inter-beat (RR) interval (SDNN); the percentage of successive RR interval differences greater than 5 ms (pNN5) and 10 ms (pNN10); low frequency (LF) and high frequency (HF).ResultsExposure to MWCNTs increased the percentage of differences between adjacent R-R intervals over 10 ms (pNN10) (p < 0.01), RMSSD (p < 0.01), LF (p < 0.05) and HF (p < 0.01).ConclusionsInhalation of MWCNTs significantly alters the balance between sympathetic and parasympathetic nervous system. Whether such transient alterations in autonomic nervous performance would alter cardiovascular function and raise the risk of cardiovascular events in people with pre-existing cardiovascular conditions warrants further study.

Risk of Major Cardiovascular Events in People with Down Syndrome.

BackgroundImproved medical care over more than five decades has markedly increased life expectancy, from 12 years to approximately 60 years, in people with Down syndrome (DS). With increased survival into late adulthood, there is now a greater need for the medical care of people with DS to prevent and treat aging-related disorders. In the wider population, acquired cardiovascular diseases such as stroke and coronary heart disease are common with increasing age, but the risks of these diseases in people with DS are unknown. There are no population-level data on the incidence of acquired major cerebrovascular and coronary diseases in DS, and no data examining how cardiovascular comorbidities or risk factors in DS might impact on cardiovascular event incidence. Such data would be also valuable to inform health care planning for people with DS. Our objective was therefore to conduct a population-level matched cohort study to quantify the risk of incident major cardiovascular events in DS.Methods and FindingsA population-level matched cohort study compared the risk of incident cardiovascular events between hospitalized patients with and without DS, adjusting for sex, and vascular risk factors. The sample was derived from hospitalization data within the Australian state of Victoria from 1993–2010. For each DS admission, 4 exact age-matched non-DS admissions were randomly selected from all hospitalizations within a week of the relevant DS admission to form the comparison cohort. There were 4,081 people with DS and 16,324 without DS, with a total of 212,539 person-years of observation. Compared to the group without DS, there was a higher prevalence in the DS group of congenital heart disease, cardiac arrhythmia, dementia, pulmonary hypertension, diabetes and sleep apnea, and a lower prevalence of ever-smoking. DS was associated with a greater risk of incident cerebrovascular events (Risk Ratio, RR 2.70, 95% CI 2.08, 3.53) especially among females (RR 3.31, 95% CI 2.21, 4.94) and patients aged ≤50 years old. The association of DS with ischemic strokes was substantially attenuated on adjustment for cardioembolic risk (RR 1.93, 95% CI 1.04, 3.20), but unaffected by adjustment for atherosclerotic risk. DS was associated with a 40–70% reduced risk of any coronary event in males (RR 0.58, 95% CI 0.40, 0.84) but not in females (RR 1.14, 95% CI 0.73, 1.77).ConclusionsDS is associated with a high risk of stroke, expressed across all ages. Ischemic stroke risk in DS appears mostly driven by cardioembolic risk. The greater risk of hemorrhagic stroke and lower risk of coronary events (in males) in DS remain unexplained.

The effect of sibutramine prescribing in routine clinical practice on cardiovascular outcomes: a cohort study in the United Kingdom.

Background/Objectives:The marketing authorization for the weight loss drug sibutramine was suspended in 2010 following a major trial that showed increased rates of non-fatal myocardial infarction and cerebrovascular events in patients with pre-existing cardiovascular disease. In routine clinical practice, sibutramine was already contraindicated in patients with cardiovascular disease and so the relevance of these influential clinical trial findings to the ‘real World' population of patients receiving or eligible for the drug is questionable. We assessed rates of myocardial infarction and cerebrovascular events in a cohort of patients prescribed sibutramine or orlistat in the United Kingdom.Subjects/Methods:A cohort of patients prescribed weight loss medication was identified within the Clinical Practice Research Datalink. Rates of myocardial infarction or cerebrovascular event, and all-cause mortality were compared between patients prescribed sibutramine and similar patients prescribed orlistat, using both a multivariable Cox proportional hazard model, and propensity score-adjusted model. Possible effect modification by pre-existing cardiovascular disease and cardiovascular risk factors was assessed.Results:Patients prescribed sibutramine (N=23 927) appeared to have an elevated rate of myocardial infarction or cerebrovascular events compared with those taking orlistat (N=77 047; hazard ratio 1.69, 95% confidence interval 1.12–2.56). However, subgroup analysis showed the elevated rate was larger in those with pre-existing cardiovascular disease (hazard ratio 4.37, 95% confidence interval 2.21–8.64), compared with those with no cardiovascular disease (hazard ratio 1.52, 95% confidence interval 0.92–2.48, P-interaction=0.0076). All-cause mortality was not increased in those prescribed sibutramine (hazard ratio 0.67, 95% confidence interval 0.34–1.32).Conclusions:Sibutramine was associated with increased rates of acute cardiovascular events in people with pre-existing cardiovascular disease, but there was a low absolute risk in those without. Sibutramine's marketing authorization may have, therefore, been inappropriately withdrawn for people without cardiovascular disease.

Change in daily ambulatory activity and cardiovascular events in people with impaired glucose tolerance.

Patients with pre-diabetes have a tenfold higher risk of developing Type 2 DM and a twofold higher risk of developing coronary heart disease compared to non-diabetics. Interventions targeted at those in an early stage of impaired glucose metabolism can delay or prevent diabetes. Effects of these interventions on cardiovascular outcome are unknown. This article aims to review current and available data on lifestyle intervention, specifically physical activity, on cardiovascular outcomes in populations at risk for diabetes. We searched PubMed database from 1990 to present with focus on more recent literature published over the last 2years. Various permutations of keywords used included glucose intolerance, pre-diabetes, diabetes, lifestyle modifications, physical activity, and cardiovascular disease. Intensive glycemic control, specific medications, and lifestyle intervention including increase in physical activity have been evaluated in diabetes and pre-diabetes. Most studies we reviewed showed that these interventions prevented progression of pre-diabetes to diabetes and improved cardiovascular risk surrogate measures. Direct decrease in cardiovascular mortality, non-fatal stroke, and non-fatal myocardial infarctions was shown in one recent trial. Increase in physical activity has a positive effect on decreasing cardiovascular risk by modifying several important risk factors and may decrease risk of events in pre-diabetics. More randomized high power trials are needed to verify and characterize these effects.

Hypoglycemia and risk of cardiovascular disease and all-cause mortality in insulin-treated people with type 1 and type 2 diabetes: a cohort study.

Hypoglycemia has been associated with an increased risk of cardiovascular (CV) events and all-cause mortality. This study assessed whether, in a nationally representative population, there is an association between hypoglycemia, the risk of CV events, and all-cause mortality among insulin-treated people with type 1 diabetes or type 2 diabetes. This retrospective cohort study used data from the Clinical Practice Research Datalink database and included all insulin-treated patients (≥30 years of age) with a diagnosis of diabetes. In patients who experienced hypoglycemia, hazard ratios (HRs) for CV events in people with type 1 diabetes were 1.51 (95% CI 0.83, 2.75; P = ns) and 1.61 (1.17, 2.22), respectively, for those with and without a history of CV disease (CVD) before the index date. In people with type 2 diabetes, the HRs for patients with and without a history of CVD were 1.60 (1.21, 2.12) and 1.49 (1.23, 1.82), respectively. For all-cause mortality, HRs in people with type 1 diabetes were 1.98 (1.25, 3.17), and 2.03 (1.66, 2.47), respectively, for those with and without a history of CVD. Among people with type 2 diabetes, HRs were 1.74 (1.39, 2.18) and 2.48 (2.21, 2.79), respectively, for those with and without a history of CVD. The median time (interquartile range) from first hypoglycemia event to first CV event was 1.5 years (0.5, 3.5 years) and 1.5 years (0.5, 3.0 years), respectively, for people with type 1 and type 2 diabetes. Hypoglycemia is associated with an increased risk of CV events and all-cause mortality in insulin-treated patients with diabetes. The relationship between hypoglycemia and CV outcomes and mortality exists over a long period.

Obesity, Cardiovascular and All-Cause Mortaliy in Chronic Kidney Disease - A Systematic Review and Meta-Analysis.

Background: The role of obesity as a risk factor for premature cardiovascular disease and death in people with chronic kidney disease (CKD) is uncertain due to inconsistent findings across the spectrum of CKD, and among published studies. Aim: Our study aimed to determine the association between obesity measured by body mass index (BMI), waist to hip ratio (WHR) and waist circumference (WC) and risk of death, cardiovascular mortality, and non-fatal cardiovascular events in people with CKD, stratified by stage, and to compare the prognostic strength of the various measures of obesity. Methods: MEDLINE and Embase were searched without language restriction through to May 2013. Hand searches were also conducted. Data were summarised using random effects models where possible. Results: Of the 3413 citations identified, a total of 94 cohorts (n=859,842 participants) assessed the association of one or more measures of obesity and all-cause and cause-specific mortality or cardiovascular outcome in patients with CKD. For every 1 kg/m2 increase in BMI, there was a 3% reduction in all-cause mortality and 4% reduction in cardiovascular mortality in CKD-dialysis (HR 0.97; 95%CI 0.96-0.98 and HR 0.96; 95%CI 0.92-1.00 respectively). In CKD-predialysis, for every 1 kg/m2 increase in BMI there was a 2% reduction in all-cause mortality (HR 0.98; 95%CI 0.0.96-1.00). There were no significant relationship between BMI and mortality in transplanted patients (HR 1.01 95%CI 0.97-1.05). Five cohort studies in total assessed the association between WHR, WC and all-cause mortality but no robust conclusions could be made. Incomplete reporting of prognostic factor and outcome measurement assessment were major limitations of the available studies. Conclusion and Relevance: Pre-dialysis and dialysis patients with a low BMI are at higher risk of mortality and cardiovascular mortality. BMI is not associated with post-transplant mortality. Higher BMI in potential recipients should therefore not preclude this group from consideration for transplantation. Further research is needed to determine if the lack of association between BMI and outcomes in transplanted patients is related to BMI being a poor measure of obesity.

Risk of death following kidney allograft failure: a systematic review and meta-analysis of cohort studies.

People with kidney allograft failure represent an increasing fraction of all those starting dialysis therapy. We sought to summarize prognosis following kidney allograft failure and identify potentially beneficial interventions or modifiable risk factors. We searched MEDLINE and EMBASE (inception to 1 October 2013) and article reference lists without language restriction and selected cohort studies of all-cause mortality and fatal infection-related and cardiovascular events in people starting dialysis following kidney allograft failure. Two reviewers independently extracted data on study design, participant characteristics, dialysis modality, transplant nephrectomy, immunosuppression strategy, transplant-naive comparators and risk of bias. Discrepancies were resolved with a third reviewer. Forty studies comprising 249 716 participants met the inclusion criteria. The first year of dialysis therapy was associated with the highest mortality. By random effects meta-analysis, annual risk of death, from years 1 to 4, was 0.12 [95% confidence interval (95% CI): 0.09-0.15], 0.06 (95% CI: 0.05-0.07), 0.05 (95% CI: 0.04-0.06) and 0.05 (95% CI: 0.04-0.06), respectively. We found high heterogeneity in each meta-analysis, which remained unexplained by prespecified subgroup analyses. We could not find sufficient information to summarize the risk for fatal infection-related and cardiovascular events, or to test the role of transplant nephrectomy or different immunosuppressive strategies. Risk of bias was high, especially participation bias. Mortality is higher during the first year of dialysis treatment following kidney allograft failure than in subsequent years. Insufficient data are available to assess factors or interventions potentially impacting prognosis following kidney allograft failure. In a culture promoting transplantation, clinical research of different models of care in this growing high-risk population should be a research priority.

All-cause mortality and serious cardiovascular events in people with hip and knee osteoarthritis: a population based cohort study

Background Because individuals with osteoarthritis (OA) avoid physical activities that exacerbate symptoms, potentially increasing risk for cardiovascular disease (CVD) and death, we assessed the relationship between OA disability and these outcomes. Methods In a population cohort aged 55+ years with at least moderately severe symptomatic hip and/or knee OA, OA disability (Western Ontario McMaster Universities (WOMAC) OA scores; Health Assessment Questionnaire (HAQ) walking score; use of walking aids) and other covariates were assessed by questionnaire. Survey data were linked to health administrative data to determine the relationship between baseline OA symptom severity to all-cause mortality and occurrence of a composite CVD outcome (acute myocardial infarction, coronary revascularization, heart failure, stroke or transient ischemic attack) over a median follow-up of 13.2 and 9.2 years, respectively. Results Of 2156 participants, 1,236 (57.3%) died and 822 (38.1%) experienced a CVD outcome during follow-up. Higher (worse) baseline WOMAC function scores and walking disability were independently associated with a higher all-cause mortality (adjusted hazard ratio, aHR, per 10-point increase in WOMAC function score 1.04, 95% confidence interval, CI 1.01–1.07, p = 0.004; aHR per unit increase in HAQ walking score 1.30, 95% CI 1.22–1.39, p<0.001; and aHR for those using versus not using a walking aid 1.51, 95% CI 1.34–1.70, p<0.001). In survival analysis, censoring on death, risk of our composite CVD outcome was also significantly and independently associated with greater baseline walking disability ((aHR for use of a walking aid = 1.27, 95% CI 1.10–1.47, p = 0.001; aHR per unit increase in HAQ walking score = 1.17, 95% CI 1.08–1.27, p<0.001). Conclusions Among individuals with hip and/or knee OA, severity of OA disability was associated with a significant increase in all-cause mortality and serious CVD events after controlling for multiple confounders. Research is needed to elucidate modifiable mechanisms.

Characterisation of pain-related behaviours in association with joint pathology in an 8-week antigen-induced arthritis model

s / Osteoarthritis and Cartilage 22 (2014) S7–S56 S37 articular antigen leads to additional pain-related behaviours. This approach should enable us to dissect relationships between specific pain pathways and joint pathology. 54 PAIN SIGNALLING IN RODENT JOINTS BY SERINE PROTEASES J.J. McDougall, A. Reid, F.A. Russell. Dalhousie Univ., Halifax, NS, Canada Purpose: Serine proteases modulate pain by either activating or disarming protease-activated receptors (PARs). The aim of the present study was to assess the effect of two serine proteases (cathepsin G and neutrophil elastase) on knee joint mechanosensitivity and pain in rodents. Methods: Electrophysiological recordings from knee joint primary afferents were carried out in deeply anaesthetised male Wistar rats in response to normal and hyper-rotation of the knee. Animals were treated with either normal or denatured cathepsin G (1ng 10mg; close intra-arterial injection) and nerve recordings repeated. In separate experiments, the effect of intra-articular injection of human neutrophil elastase (1-50mg rat; 1-5mg mouse) on pain behaviour in awake and unrestrained Wistar rats and c57bl/6 mice was determined by measurement of hindlimb incapacitance (weight bearing) and von Frey hair tactile allodynia. Results: Peripheral administration of cathepsin G caused a dosedependent reduction in joint mechanosensitivity compared to boiled enzyme, which had no discernible effect (P 0.8). As expected, KOOS is more strongly correlated with physical subscales of the SF-36 across different conditions, interventions and languages. While KOOS demonstrates large effect sizes post-surgery, future studies should prioritise evaluation of longitudinal validity to adhere with updated recommendations for evaluation of measurement properties. 56 ALL-CAUSE MORTALITY AND SERIOUS CARDIOVASCULAR EVENTS IN PEOPLE WITH HIP AND KNEE OSTEOARTHRITIS: A POPULATION BASED COHORT STUDY G.A. Hawker yz, R. Croxford x, A.S. Bierman y, P.J. Harvey yz, B. Ravi y, I. Stanaitis z, L.L. Lipscombe yz. yUniv. of Toronto, Toronto, ON, Canada; zWomen’s Coll. Hosp., Toronto, ON, Canada; x Inst. for Clinical Evaluative Sci. (ICES), Toronto, ON, Canada Purpose: Osteoarthritis (OA) is under-treated in part due to the high coprevalence of other chronic conditions. Approximately 90% of people aged 65þ years with symptomatic OA have at least one additional chronic condition; OA and cardiovascular disease, CVD, are among the most common dyads seen in clinical practice. CVD, in particular, may be perceived as precluding the use of OA therapies (e.g. NSAIDs). Inadequately treated, people with OA may manage their OA by avoiding activities, like walking, that exacerbate symptoms. Reduced physical activity may further increase these individuals’ CVD risk. We therefore examined the contribution of OA disability to other CVD risk factors, including prior history of a CVD event, on risk for CVD events. Methods: This retrospective cohort study used data from a population cohortwith symptomatic hip and kneeOA that was recruited from 199698 through a screening survey of 100% of the population aged 55þ years in twoOntario regions (n1⁄42225hadOAconfirmedonexamination andxray). The baseline survey assessed: socio-demographics; smoking; selfreportedheight,weight andNSAIDuse; comorbidity (includingphysician diagnosis and treatment in thepast year forhighbloodpressure, diabetes, andheartproblems); andmentalhealth status.OAdisabilitywas assessed using theWOMAC function subscale, useof awalkingaid (yes/no) and the Health Assessment Questionnaire walking disability subscale (0–3; higher scores indicate greater disability). The current study used baseline surveys linked to provincial health administrative databases.

Pain signalling in rodent joints by serine proteases

s / Osteoarthritis and Cartilage 22 (2014) S7–S56 S37 articular antigen leads to additional pain-related behaviours. This approach should enable us to dissect relationships between specific pain pathways and joint pathology. 54 PAIN SIGNALLING IN RODENT JOINTS BY SERINE PROTEASES J.J. McDougall, A. Reid, F.A. Russell. Dalhousie Univ., Halifax, NS, Canada Purpose: Serine proteases modulate pain by either activating or disarming protease-activated receptors (PARs). The aim of the present study was to assess the effect of two serine proteases (cathepsin G and neutrophil elastase) on knee joint mechanosensitivity and pain in rodents. Methods: Electrophysiological recordings from knee joint primary afferents were carried out in deeply anaesthetised male Wistar rats in response to normal and hyper-rotation of the knee. Animals were treated with either normal or denatured cathepsin G (1ng 10mg; close intra-arterial injection) and nerve recordings repeated. In separate experiments, the effect of intra-articular injection of human neutrophil elastase (1-50mg rat; 1-5mg mouse) on pain behaviour in awake and unrestrained Wistar rats and c57bl/6 mice was determined by measurement of hindlimb incapacitance (weight bearing) and von Frey hair tactile allodynia. Results: Peripheral administration of cathepsin G caused a dosedependent reduction in joint mechanosensitivity compared to boiled enzyme, which had no discernible effect (P 0.8). As expected, KOOS is more strongly correlated with physical subscales of the SF-36 across different conditions, interventions and languages. While KOOS demonstrates large effect sizes post-surgery, future studies should prioritise evaluation of longitudinal validity to adhere with updated recommendations for evaluation of measurement properties. 56 ALL-CAUSE MORTALITY AND SERIOUS CARDIOVASCULAR EVENTS IN PEOPLE WITH HIP AND KNEE OSTEOARTHRITIS: A POPULATION BASED COHORT STUDY G.A. Hawker yz, R. Croxford x, A.S. Bierman y, P.J. Harvey yz, B. Ravi y, I. Stanaitis z, L.L. Lipscombe yz. yUniv. of Toronto, Toronto, ON, Canada; zWomen’s Coll. Hosp., Toronto, ON, Canada; x Inst. for Clinical Evaluative Sci. (ICES), Toronto, ON, Canada Purpose: Osteoarthritis (OA) is under-treated in part due to the high coprevalence of other chronic conditions. Approximately 90% of people aged 65þ years with symptomatic OA have at least one additional chronic condition; OA and cardiovascular disease, CVD, are among the most common dyads seen in clinical practice. CVD, in particular, may be perceived as precluding the use of OA therapies (e.g. NSAIDs). Inadequately treated, people with OA may manage their OA by avoiding activities, like walking, that exacerbate symptoms. Reduced physical activity may further increase these individuals’ CVD risk. We therefore examined the contribution of OA disability to other CVD risk factors, including prior history of a CVD event, on risk for CVD events. Methods: This retrospective cohort study used data from a population cohortwith symptomatic hip and kneeOA that was recruited from 199698 through a screening survey of 100% of the population aged 55þ years in twoOntario regions (n1⁄42225hadOAconfirmedonexamination andxray). The baseline survey assessed: socio-demographics; smoking; selfreportedheight,weight andNSAIDuse; comorbidity (includingphysician diagnosis and treatment in thepast year forhighbloodpressure, diabetes, andheartproblems); andmentalhealth status.OAdisabilitywas assessed using theWOMAC function subscale, useof awalkingaid (yes/no) and the Health Assessment Questionnaire walking disability subscale (0–3; higher scores indicate greater disability). The current study used baseline surveys linked to provincial health administrative databases.

All-Cause Mortality and Serious Cardiovascular Events in People with Hip and Knee Osteoarthritis: A Population Based Cohort Study

BackgroundBecause individuals with osteoarthritis (OA) avoid physical activities that exacerbate symptoms, potentially increasing risk for cardiovascular disease (CVD) and death, we assessed the relationship between OA disability and these outcomes.MethodsIn a population cohort aged 55+ years with at least moderately severe symptomatic hip and/or knee OA, OA disability (Western Ontario McMaster Universities (WOMAC) OA scores; Health Assessment Questionnaire (HAQ) walking score; use of walking aids) and other covariates were assessed by questionnaire. Survey data were linked to health administrative data to determine the relationship between baseline OA symptom severity to all-cause mortality and occurrence of a composite CVD outcome (acute myocardial infarction, coronary revascularization, heart failure, stroke or transient ischemic attack) over a median follow-up of 13.2 and 9.2 years, respectively.ResultsOf 2156 participants, 1,236 (57.3%) died and 822 (38.1%) experienced a CVD outcome during follow-up. Higher (worse) baseline WOMAC function scores and walking disability were independently associated with a higher all-cause mortality (adjusted hazard ratio, aHR, per 10-point increase in WOMAC function score 1.04, 95% confidence interval, CI 1.01–1.07, p = 0.004; aHR per unit increase in HAQ walking score 1.30, 95% CI 1.22–1.39, p<0.001; and aHR for those using versus not using a walking aid 1.51, 95% CI 1.34–1.70, p<0.001). In survival analysis, censoring on death, risk of our composite CVD outcome was also significantly and independently associated with greater baseline walking disability ((aHR for use of a walking aid = 1.27, 95% CI 1.10–1.47, p = 0.001; aHR per unit increase in HAQ walking score = 1.17, 95% CI 1.08–1.27, p<0.001).ConclusionsAmong individuals with hip and/or knee OA, severity of OA disability was associated with a significant increase in all-cause mortality and serious CVD events after controlling for multiple confounders. Research is needed to elucidate modifiable mechanisms.

Healthy lifestyle for metabolic health: no more excuse!

Metabolic syndrome (MS) constitutes a growing problem worldwide. Whether or not one accepts this condition as a by-product of our modern lifestyle, the concept of MS continues to gain acceptance. There is a quite general agreement that its rising prevalence is largely due to the increasing incidence of obesity and associated lifestyle factors. The increased risk of type 2 diabetes and cardiovascular events in people with MS is well known [1]; recent epidemiological evidence also suggests a positive association between MS and the risk of some common cancer [2–4]. Studies of the beneficial health effects of physical activity (PA) date back to the 1950s [5] and have been replicated in large cohorts. Overall, PA is associated with many health-related benefits, including a reduced risk of developing several chronic diseases such as obesity, cardiovascular disease, type 2 diabetes, and cancer. Recommendations for PA and health have included 30 min/day (or more) of at least moderate-intensity PA on most days of the week with respect to cardiovascular benefits [6]. Data from the U.S. National Health and Nutrition Examination Survey (NHANES) indicate that the vast majority of daily non-sleeping time is spent in either sedentary behavior (58 %) or light-intensity activity (39 %), and only 3 % in exercise time [7]. Cross-sectional studies found an inverse gradient between amount of PA and MS. Guidelines support that at least 150 min of moderate-intensity PA per week is associated with a lower prevalence of MS and diabetes [8]. The EPIC Norfolk prospective population study investigated the association among PA, MS, and the risk of future coronary heart disease (CHD) and mortality due to CHD in 10,134 middle-aged men and women [9]. The prevalence of MS was 37.6 % in men and 30.2 % in women. There was no longer a significant difference in CHD event rate between men with MS who were active and men without MS who were inactive, indicating that PA lowers the CHD risk associated with MS. He and coworkers [10] did the first meta-analysis of prospective studies, including 64,353 participants and 11,271 incident cases reporting the association between leisure-time physical activity (LTPA) and risk of future MS. Compared to inactive people, a high level of LTPA was associated with a 20 % reduced risk of incident MS independent of sex, definition of MS, and duration of follow-up; on the other hand, the association between moderate level of LTPA and incident MS was modest (5 % reduced risk), except in men (12 % reduced risk) and in studies with a long follow-up ([10 years). The aim to focus upon LTPA was not by chance: PA at work, walking, and bicycling have declined dramatically in industrial and urban societies. This is an important reason why more recent epidemiologic studies in high-income countries have focused on leisure-time activity, with less emphasis on K. Esposito (&) Department of Clinical and Experimental Medicine, and Diabetes Canter, Second University of Naples, Piazza L. Miraglia 2, 80138 Naples, Italy e-mail: katherine.esposito@unina2.it

Association of red cell distribution width, haematocrit and other RBC indices with coronay artery disease: A case control study

Background: Coronary artery disease (CAD) is mainly caused by atherosclerosis and its complications. Red blood cell distribution width (RDW) is a numerical measure of the variability in size of circulating erythrocytes. Several studies reported a strong, independent relation between higher levels of RDW, hematocrit (Hct), and the risk of death and cardiovascular events in people with prior CAD. We tested the hypothesis that RDW, Hct, and other red blood corpuscle (RBC) indices are associated with CAD. Hence, we measured RDW, Hct, and other RBC indices in AMI and stable CAD (SCAD) and compared them with age- and sex-matched controls.Objectives: To study the changes in RDW and RBC indices in acute myocardial infarction (AMI) and SCAD and compare them with age- and sex-matched controls.Materials and Methods: This was a comparative study of 128 subjects (39 patients with AMI, 24 patients with SCAD, and 65 controls). Venous sample were drawn from AMI subjects on admission (within 6 h of chest pain) and collected in standardized ethylenediaminetetraacetic acid (EDTA) sample tubes. RDW and RBC indices were assayed within 30 min of blood collection, using Sysmex KX21-N autoanalyzer. Venous samples were also drawn from stable CAD patients who were admitted for angiography and subject attending routine checkups.Results: There was no significant difference in RDW in patients with CAD (14.12 ± 1.31%) as compared to controls (15.62 ± 6.51%). There was no significant difference in RWD in patients with AMI (14.36 ± 1.4%) as compared to stable CAD (13.7 ± 1.09%) and controls (15.62 ± 6.51%). There was no significant difference in Hct in patients with CAD (43.16 ± 5%) as compared to controls (41.9 ± 6.9%).Conclusions: There was no association between RWD, Hct, and other RBC indices with CAD, AMI, and stable CAD.

Association between change in daily ambulatory activity and cardiovascular events in people with impaired glucose tolerance (NAVIGATOR trial): a cohort analysis

The extent to which change in physical activity can modify the risk of cardiovascular disease in individuals at high cardiovascular risk is uncertain. We investigated whether baseline and change in objectively-assessed ambulatory activity is associated with the risk of a cardiovascular event in individuals at high cardiovascular risk with impaired glucose tolerance. We assessed prospective data from the NAVIGATOR trial involving 9306 individuals with impaired glucose tolerance who were recruited in 40 countries between January, 2002, and January, 2004. Participants also either had existing cardiovascular disease (if age ≥50 years) or at least one additional cardiovascular risk factor (if age ≥55 years). Participants were followed-up for cardiovascular events (defined as cardiovascular mortality, non-fatal stroke, or myocardial infarction) for 6 years on average and had ambulatory activity assessed by pedometer at baseline and 12 months. Adjusted Cox proportional hazard models quantified the association of baseline and change in ambulatory activity (from baseline to 12 months) with the risk of a subsequent cardiovascular event, after adjustment for each other and potential confounding variables. This study is registered with ClinicalTrials.govNCT00097786. During 45,211 person-years follow-up, 531 cardiovascular events occurred. Baseline ambulatory activity (hazard ratio [HR] per 2000 steps per day 0·90, 95% CI 0·84-0·96) and change in ambulatory activity (0·92, 0·86-0·99) were inversely associated with the risk of a cardiovascular event. Results for change in ambulatory activity were unaffected when also adjusted for changes in body-mass index and other potential confounding variables at 12 months. In individuals at high cardiovascular risk with impaired glucose tolerance, both baseline levels of daily ambulatory activity and change in ambulatory activity display a graded inverse association with the subsequent risk of a cardiovascular event. Novartis Pharmaceuticals.

Blood pressure lowering and major cardiovascular events in people with and without chronic kidney disease: meta-analysis of randomised controlled trials

Objective To define the cardiovascular effects of lowering blood pressure in people with chronic kidney disease.Design Collaborative prospective meta-analysis of randomised trials.Data sources and eligibility Participating randomised trials of drugs...

Adherence to psychiatric treatments and the public image of psychiatry

Adherence to psychiatric treatments and the public image of psychiatry

Serum phosphate as a risk factor for cardiovascular events in people with and without chronic kidney disease: a large community based cohort study.

BackgroundSerum phosphate is a known risk factor for cardiovascular events and mortality in people with chronic kidney disease (CKD), however data on the association of these outcomes with serum phosphate in the general population are scarce. We investigate this relationship in people with and without CKD in a large community-based population.MethodsThree groups from an adult cohort of the Quality Improvement in Chronic Kidney Disease (QICKD) cluster randomised trial (ISRCTN56023731) were followed over a period of 2.5 years: people with normal renal function (N = 24,184), people with CKD stages 1–2 (N = 20,356), and people with CKD stages 3–5 (N = 13,292). We used a multilevel logistic regression model to determine the association between serum phosphate, in these groups, and a composite outcome of all-cause mortality, cardiovascular events, and advanced coronary artery disease. We adjusted for known cardiovascular risk factors.FindingsHigher phosphate levels were found to correlate with increased cardiovascular risk. In people with normal renal function and CKD stages 1–2, Phosphate levels between 1.25 and 1.50 mmol/l were associated with increased cardiovascular events; odds ratio (OR) 1.36 (95% CI 1.06–1.74; p = 0.016) in people with normal renal function and OR 1.40 (95% CI 1.09–1.81; p = 0.010) in people with CKD stages 1–2. Hypophosphatemia (<0.75 mmol/l) was associated with fewer cardiovascular events in people with normal renal function; OR 0.59 (95% CI 0.36–0.97; p = 0.049). In people with CKD stages 3–5, hyperphosphatemia (>1.50 mmol/l) was associated with increased cardiovascular risk; OR 2.34 (95% CI 1.64–3.32; p<0.001). Other phosphate ranges were not found to have a significant impact on cardiovascular events in people with CKD stages 3–5.ConclusionsSerum phosphate is associated with cardiovascular events in people with and without CKD. Further research is required to determine the mechanisms underlying these associations.