Long-term follow-up of cognitive function and activities of daily living in older people: a feasibility study in the PROSPER cohort

<p>Background: The Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) considered the benefits of pravastatin therapy and provided insights into cognitive decline/disability in older people but follow-up was short.</p> <p>Methods: We performed a feasibility study of 300 PROSPER recruits, 7 years after the trial finished. The subject’s general practitioner provided basic follow-up data. Telephone contact with participants established cognition/functional level. Relatives of those unsuitable for contact were asked to complete postal questionnaires.</p> <p>Results: Of 300 participants we established 132 were alive, 135 dead and 33 lost to follow-up. Of 132 survivors data were obtained for 78 participants by telephone, 10 participants with GP diagnosis of dementia, and 3 participants whose relative provided information. Therefore cognitive function was determined in 69% of survivors and functional ability in 61%.</p> <p>Conclusions: It was feasible to perform long-term follow-up of cognition/functional ability in the majority of survivors from a large randomised controlled trial.</p&gt

Efficacy and safety of Cannabidiol and Tetrahydrocannabivarin on glycemic and lipid parameters in patients with Type 2 diabetes: a randomized, double-blind, placebo-controlled, parallel group pilot study

OBJECTIVE Cannabidiol (CBD) and Δ9-tetrahydrocannabivarin (THCV) are nonpsychoactive phytocannabinoids affecting lipid and glucose metabolism in animal models. This study set out to examine the effects of these compounds in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS In this randomized, double-blind, placebo-controlled study, 62 subjects with noninsulin-treated type 2 diabetes were randomized to five treatment arms: CBD (100 mg twice daily), THCV (5 mg twice daily), 1:1 ratio of CBD and THCV (5 mg/5 mg, twice daily), 20:1 ratio of CBD and THCV (100 mg/5 mg, twice daily), or matched placebo for 13 weeks. The primary end point was a change in HDL-cholesterol concentrations from baseline. Secondary/tertiary end points included changes in glycemic control, lipid profile, insulin sensitivity, body weight, liver triglyceride content, adipose tissue distribution, appetite, markers of inflammation, markers of vascular function, gut hormones, circulating endocannabinoids, and adipokine concentrations. Safety and tolerability end points were also evaluated. RESULTS Compared with placebo, THCV significantly decreased fasting plasma glucose (estimated treatment difference [ETD] = −1.2 mmol/L; P < 0.05) and improved pancreatic β-cell function (HOMA2 β-cell function [ETD = −44.51 points; P < 0.01]), adiponectin (ETD = −5.9 × 106 pg/mL; P < 0.01), and apolipoprotein A (ETD = −6.02 μmol/L; P < 0.05), although plasma HDL was unaffected. Compared with baseline (but not placebo), CBD decreased resistin (−898 pg/ml; P < 0.05) and increased glucose-dependent insulinotropic peptide (21.9 pg/ml; P < 0.05). None of the combination treatments had a significant impact on end points. CBD and THCV were well tolerated. CONCLUSIONS THCV could represent a new therapeutic agent in glycemic control in subjects with type 2 diabetes

Are markers of inflammation more strongly associated with risk for fatal than for nonfatal vascular events?

&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; Circulating inflammatory markers may more strongly relate to risk of fatal versus nonfatal cardiovascular disease (CVD) events, but robust prospective evidence is lacking. We tested whether interleukin (IL)-6, C-reactive protein (CRP), and fibrinogen more strongly associate with fatal compared to nonfatal myocardial infarction (MI) and stroke.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods and Findings:&lt;/b&gt; In the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER), baseline inflammatory markers in up to 5,680 men and women aged 70-82 y were related to risk for endpoints; nonfatal CVD (i.e., nonfatal MI and nonfatal stroke [n = 672]), fatal CVD (n = 190), death from other CV causes (n = 38), and non-CVD mortality (n = 300), over 3.2-y follow-up. Elevations in baseline IL-6 levels were significantly (p = 0.0009; competing risks model analysis) more strongly associated with fatal CVD (hazard ratio [HR] for 1 log unit increase in IL-6 1.75, 95% confidence interval [CI] 1.44-2.12) than with risk of nonfatal CVD (1.17, 95% CI 1.04-1.31), in analyses adjusted for treatment allocation. The findings were consistent in a fully adjusted model. These broad trends were similar for CRP and, to a lesser extent, for fibrinogen. The results were also similar in placebo and statin recipients (i.e., no interaction). The C-statistic for fatal CVD using traditional risk factors was significantly (+0.017; p&lt;0.0001) improved by inclusion of IL-6 but not so for nonfatal CVD events (p = 0.20).&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; In PROSPER, inflammatory markers, in particular IL-6 and CRP, are more strongly associated with risk of fatal vascular events than nonfatal vascular events. These novel observations may have important implications for better understanding aetiology of CVD mortality, and have potential clinical relevance.&lt;/p&gt

Do vascular risk factors explain the association between socioeconomic status and stroke incidence: a meta-analysis

&lt;p&gt;Background: Reduced socioeconomic status (SES) is associated with an increased risk of stroke, although the mechanism is not clear. It may be that those with lower SES have a greater burden of classic vascular risk factors.&lt;/p&gt; &lt;p&gt;Methods: Our aim was to quantify the extent to which classic vascular risk factors explain the association between SES and stroke incidence. We conducted a systematic review and meta-analysis of studies examining the association of SES and stroke incidence, where classic vascular risk factors were considered. Searching MEDLINE, EMBASE and the Cochrane Library from 1980 onwards we identified 17 studies, 12 of these studies provided sufficient information to allow a meta-analysis. From each study the increased risk of stroke incidence, where the lowest socioeconomic category was compared with the highest, was recorded and pooled. The stroke incidence risks, adjusted for grouped classic risk factors, were also pooled. Review Manager 5 software was used for all analyses and results were analysed using hazard ratios (HR, 95% confidence interval, 95% CI) with a random effects model.&lt;/p&gt; &lt;p&gt;Results: Those with a lower SES were more likely to have a stroke (HR 1.67; 95% CI 1.46-1.91). Additional risk was reduced, but not eliminated, when classic vascular risk factors were adjusted for (HR 1.31; 95% CI 1.16-1.48).&lt;/p&gt; &lt;p&gt;Conclusion: Low SES is associated with an increased risk of stroke that is partly explained by known classic vascular risk factors.&lt;/p&gt

Socioeconomic status and transient ischaemic attack / stroke: a prospective observational study

&lt;p&gt;Background: Lower socioeconomic status (SES) is associated with an increased risk of stroke but the mechanisms are unclear. We aimed to determine whether low-SES stroke/transient ischaemic attack (TIA) patients have a greater burden of vascular risk factors/co-morbidity and reduced health care access.&lt;/p&gt; &lt;p&gt;Methods: We prospectively studied 467 consecutive stroke and TIA patients from 3 Scottish hospitals (outpatients and inpatients) during 2007/2008. We recorded vascular risk factors, stroke severity, co-morbidity measures, investigations and health service utilisation. SES was derived from postcodes using Scottish Neighbourhood Statistics and analysed in quartiles.&lt;/p&gt; &lt;p&gt;Results: TIA/stroke patients in the lowest SES quartile were younger (64 years, SD 14.1) than those in the highest quartile (72 years, SD 12.9; p &#60; 0.0001). They were more likely to be current smokers (42 vs. 22%; p = 0.001) but there was no association with other vascular risk factors/co-morbidity. There was a trend for those with lower SES to have a more severe stroke [modified National Institutes of Health Stroke Scale score and interquartile range: 4 (2–6) vs. 3 (1–5); multivariate p = 0.05]. Lower SES groups were less likely to have neuro-imaging (82 vs. 90%; p = 0.036) or an electrocardiogram (72 vs. 87%; p = 0.003), but differences were no longer significant on multivariate analysis. However, there was equal access to stroke unit care.&lt;/p&gt; &lt;p&gt;Conclusions: Low-SES TIA and stroke patients are younger and have a more severe deficit; an increased prevalence of smoking is likely to be a major contributor. We found equal access to stroke unit care for low-SES patients.&lt;/p&gt

Adipocytokines and risk of stroke in older people: a nested case-control study

Background Inflammation may play an important role in atherothrombosis and in promoting cerebral damage after stroke. We hypothesized that plasma adipocytokine concentrations would be associated with risk of stroke in older people. Methods Nested case-control study from the Prospective Study of Pravastatin in the Elderly ( PROSPER). Subjects were aged 70-82 years and followed up for a mean of 3.2 years: 266 incident stroke cases ( 179 confirmed as ischaemic) were compared with 532 controls matched for age, gender and treatment allocation ( pravastatin or placebo). Adipocytokines [ adiponectin, interleukin- (IL-)18 and tumour necrosis factor (TNF)alpha] were measured on stored baseline plasma samples. Results Elevated plasma adiponectin was associated with lower risk of ischaemic stroke on univariate analysis: odds ratio ( OR) 0.78 per 1 SD increase (95% CI 0.62-0.97). There were no associations of IL- 18 or TNF alpha with risk for ischaemic or total strokes. In multivariate models the independent predictors of ischaemic stroke were prior cerebrovascular accident ( OR 2.68, 95% CI 1.60-4.50), any alcohol use (1.98, 1.33-2.94), triglycerides (1.40, 1.11-1.77), Barthel score (0.75, 0.58-0.96) and known diabetes (1.72, 1.04-2.83); adiponectin, IL- 18 and TNFa did not contribute. A similar pattern of risk was seen for total stroke. Conclusions Reduced adiponectin may have a modest role in the aetiology of ischaemic stroke in older people, however IL- 18 and TNFa are unlikely to play any important part. These adipocytokines do not have clinical predictive utility; history of prior cerebrovascular accident, known diabetes mellitus, prior disability and higher alcohol intake explain much of the stroke risk

Associations Between Thrombin Generation and the Risk of Cardiovascular Disease in Elderly Patients: Results From the PROSPER Study

Cardiolog