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Biomedical subjects

Graeme J Hankey

Publications and source records attributed to Graeme J Hankey.

At least 19 recordsLinked to original sources
PubMed2025

Cardiac Troponins and Cardiovascular Disease Risk Prediction: An Individual-Participant-Data Meta-Analysis.

BACKGROUND: The extent to which high-sensitivity cardiac troponin can predict cardiovascular disease (CVD) is uncertain. OBJECTIVES: We aimed to quantify the potential advantage of adding information on cardiac troponins to conventional risk factors in the prevention of CVD. METHODS: We meta-analyzed individual-participant data from 15 cohorts, comprising 62,150 participants without prior CVD. We calculated HRs, measures of risk discrimination, and reclassification after adding cardiac troponin T (cTnT) or I (cTnI) to conventional risk factors. The primary outcome was first-onset CVD (ie, coronary heart disease or stroke). We then modeled the implications of initiating statin therapy using incidence rates from 2.1 million individuals from the United Kingdom. RESULTS: Among participants with cTnT or cTnI measurements, 8,133 and 3,749 incident CVD events occurred during a median follow-up of 11.8 and 9.8 years, respectively. HRs for CVD per 1-SD higher concentration were 1.31 (95% CI: 1.25-1.37) for cTnT and 1.26 (95% CI: 1.19-1.33) for cTnI. Addition of cTnT or cTnI to conventional risk factors was associated with C-index increases of 0.015 (95% CI: 0.012-0.018) and 0.012 (95% CI: 0.009-0.015) and continuous net reclassification improvements of 6% and 5% in cases and 22% and 17% in noncases. One additional CVD event would be prevented for every 408 and 473 individuals screened based on statin therapy in those whose CVD risk is reclassified from intermediate to high risk after cTnT or cTnI measurement, respectively. CONCLUSIONS: Measurement of cardiac troponin results in a modest improvement in the prediction of first-onset CVD that may translate into population health benefits if used at scale.

Humans↗
PubMed2006

Association of cardiovascular risk factors and disease with depression in later life.

OBJECTIVE: The objective of this study is to determine the association between established cardiovascular risk factors and depression among older men. METHODS: The authors conducted a cross-sectional study of a community-representative sample of 5,439 men aged 71-89 years. Cardiovascular disease and risk factors assessed included history of diabetes, hypertension, angina, myocardial infarction, and stroke; current smoking; total cholesterol and fractions; triglycerides; total plasma homocysteine; and MTHFR677 genotype. Depression was defined by a Geriatric Depression Scale 15 items score of 7 or greater. RESULTS: A complete data set was available for 4,204 men, of whom 212 were depressed (5%). Men who were depressed reported higher frequency of diabetes (23.1% versus 13.2%), angina (30.2% versus 20.4%), myocardial infarction (26.2% versus 16.0%), and stroke (23.6% versus 9.1%) than nondepressed men. Participants with depression were also more likely to have plasma homocysteine above 15 mumol/L (39.1% versus 25.5%) and high triglycerides (32.1% versus 20.9%) than nondepressed subjects. Depressed older men were also more likely to be active smokers (9.9% versus 4.8%). The other factors measured in the study were not significantly associated with depression. Estimation of the population-attributable fraction (PAF) after logistic regression showed that high plasma homocysteine had the highest PAF for depression (PAF:15%, 95% confidence interval [95% CI]: 5%-23%) followed by high triglycerides (PAF: 11%, 95% CI: 2%-18%), angina (PAF: 9%, 95% CI: 2%-15%), stroke (PAF: 8%, 95% CI: 3%-13%), diabetes (PAF: 7%, 95% CI: 1%-13%), myocardial infarction (PAF: 5%, 95% CI: 0%-11%), and smoking (PAF: 5%, 95% CI: 1%-9%). CONCLUSIONS: High plasma homocysteine and triglycerides appear to account for a considerable proportion of cases of depression in older men. The successful management of these risk factors may contribute to decrease the prevalence of depression in later life.

Age of Onset↗
PubMed2006

Potential new risk factors for ischemic stroke: what is their potential?

BACKGROUND AND PURPOSE: About 60% to 80% of all ischemic strokes can be attributed to increasing blood pressure, blood cholesterol, cigarette smoking, carotid stenosis, and diabetes mellitus (atherosclerotic ischemic stroke), and atrial fibrillation and valvular heart disease (cardiogenic ischemic stroke). The aim of this review was to examine the potential role of other risk factors in the etiology of ischemic stroke. SUMMARY OF REVIEW: About 10% to 20% of atherosclerotic ischemic strokes can probably be attributed to recently established, causal risk factors for ischemic heart disease: raised apoB/apoA 1 ratio, obesity, physical inactivity, pyschosocial stress and low fruit and vegetable intake. However, their causal role remains to be proven. The direct genetic contribution of any single gene towards ischemic stroke is likely to be modest and apply in selected patients only and in combination with environmental factors or via other epistatic (gene-gene or gene-environmental) effects. CONCLUSIONS: Research resources should not be allocated disproportionately to emerging novel risk factors that may account for up to only 20% of all strokes at the expense of researching the determinants of the relatively few established causal factors that account for up to 80% of all strokes.

Brain Ischemia↗
PubMed2006

Risk of recurrent venous thromboembolism in patients with common thrombophilia: a systematic review.

The 2 most common genetic polymorphisms that predispose to a first episode of venous thromboembolism (VTE) are factor V Leiden (FVL) and prothrombin G20210A. However, the effect of these polymorphisms on the risk of recurrent VTE is unclear. We performed a meta-analysis to obtain best estimates of the relative risk of recurrent VTE associated with these genetic polymorphisms. Electronic and manual searches were used to identify cohort studies of patients with a first episode of VTE that reported the incidence of objectively confirmed recurrence following discontinuation of anticoagulation among those with or without heterozygous FVL or prothrombin G20210A polymorphism. Thirteen reports fulfilled our criteria for inclusion. Pooled results from 10 studies involving 3104 patients with first-ever VTE revealed that FVL was present in 21.4% of patients (95% confidence interval [CI], 20%-23%) and associated with an increased odds of recurrent VTE of 1.41 (95% CI, 1.14-1.75; P = .08 for heterogeneity). Pooled results from 9 studies involving 2903 patients with first-ever VTE revealed that prothrombin G20210A was present in 9.7% of patients (95% CI, 9%-11%) and associated with an increased odds of recurrent VTE of 1.72 (95% CI, 1.27-2.31; P = .19). The estimated population-attributable risk of recurrence for FVL was 9.0% (95% CI, 4.5%-13.2%) and for prothrombin G20210A was 6.7% (95% CI, 3.4%-9.9%). Heterozygous FVL and prothrombin G20210A are each associated with a significantly increased risk of recurrent VTE after a first event, but the magnitude of the increase in risk is modest and by itself is unlikely to merit extended-duration anticoagulation. These data call into question the cost-effectiveness of routine testing for these common inherited thrombophilic polymorphisms among patients with a first episode of VTE.

Factor V↗
PubMed2006

Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events.

BACKGROUND: Dual antiplatelet therapy with clopidogrel plus low-dose aspirin has not been studied in a broad population of patients at high risk for atherothrombotic events. METHODS: We randomly assigned 15,603 patients with either clinically evident cardiovascular disease or multiple risk factors to receive clopidogrel (75 mg per day) plus low-dose aspirin (75 to 162 mg per day) or placebo plus low-dose aspirin and followed them for a median of 28 months. The primary efficacy end point was a composite of myocardial infarction, stroke, or death from cardiovascular causes. RESULTS: The rate of the primary efficacy end point was 6.8 percent with clopidogrel plus aspirin and 7.3 percent with placebo plus aspirin (relative risk, 0.93; 95 percent confidence interval, 0.83 to 1.05; P=0.22). The respective rate of the principal secondary efficacy end point, which included hospitalizations for ischemic events, was 16.7 percent and 17.9 percent (relative risk, 0.92; 95 percent confidence interval, 0.86 to 0.995; P=0.04), and the rate of severe bleeding was 1.7 percent and 1.3 percent (relative risk, 1.25; 95 percent confidence interval, 0.97 to 1.61 percent; P=0.09). The rate of the primary end point among patients with multiple risk factors was 6.6 percent with clopidogrel and 5.5 percent with placebo (relative risk, 1.2; 95 percent confidence interval, 0.91 to 1.59; P=0.20) and the rate of death from cardiovascular causes also was higher with clopidogrel (3.9 percent vs. 2.2 percent, P=0.01). In the subgroup with clinically evident atherothrombosis, the rate was 6.9 percent with clopidogrel and 7.9 percent with placebo (relative risk, 0.88; 95 percent confidence interval, 0.77 to 0.998; P=0.046). CONCLUSIONS: In this trial, there was a suggestion of benefit with clopidogrel treatment in patients with symptomatic atherothrombosis and a suggestion of harm in patients with multiple risk factors. Overall, clopidogrel plus aspirin was not significantly more effective than aspirin alone in reducing the rate of myocardial infarction, stroke, or death from cardiovascular causes. (ClinicalTrials.gov number, NCT00050817.).

Adult↗
PubMed2006

Aspirin resistance.

Aspirin resistance is the inability of aspirin to reduce platelet production of thromboxane A2 and thereby platelet activation and aggregation. Increasing degrees of aspirin resistance may correlate independently with increasing risk of cardiovascular events. Aspirin resistance can be detected by laboratory tests of platelet thromboxane A2 production or platelet function that depend on platelet thromboxane production. Potential causes of aspirin resistance include inadequate dose, drug interactions, genetic polymorphisms of COX-1 and other genes involved in thromboxane biosynthesis, upregulation of non-platelet sources of thromboxane biosynthesis, and increased platelet turnover. Aspirin resistance can be overcome by treating the cause or causes, and reduced by minimising thromboxane production and activity, and blocking other pathways of platelet activation. Future research is aimed at defining aspirin resistance, developing reliable tests for it, and establishing the risk of associated cardiovascular events. Potential mechanisms of aspirin resistance can then be explored and treatments assessed.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2006

Medical treatment of peripheral arterial disease.

CONTEXT: Peripheral arterial disease (PAD) affects approximately 20% of adults older than 55 years and is a powerful predictor of myocardial infarction, stroke, and death due to vascular causes. The goals of treatment are to prevent future major coronary and cerebrovascular events and improve leg symptoms. OBJECTIVE: To review the best evidence for medical treatment of PAD. EVIDENCE ACQUISITION: MEDLINE and the Cochrane database were searched from 1990 to November 2005 for randomized trials and meta-analyses of medical treatments for PAD. References from these articles were also searched. Search terms included, singly and in combination: peripheral arterial disease, peripheral artery disease, PAD, randomized controlled trial, controlled trial, randomized, and meta-analysis. Particular attention was directed toward randomized controlled trials and meta-analyses of clinically relevant medical treatments for PAD. Outcome measures included leg symptoms (intermittent claudication and walking distance), death, and major coronary and cerebrovascular events. EVIDENCE SYNTHESIS: Symptoms of leg claudication, walking distance, and quality of life can be improved by smoking cessation (physician advice, nicotine replacement therapy, and bupropion), a structured exercise program, statin drugs, cilostazol, and angiotensin-converting enzyme inhibitors. The risk of major coronary and cerebrovascular events can be reduced through lowering blood pressure with angiotensin-converting enzyme inhibitors and other antihypertensive drugs, use of statin drugs, antiplatelet therapy with aspirin or clopidogrel, and probably by stopping smoking. CONCLUSION: The substantial and increasing burden of PAD, and its local and systemic complications, can be reduced by lifestyle modification (smoking cessation, exercise) and medical therapies (nicotine replacement therapy, bupropion, antihypertensive drugs, statins, and antiplatelet drugs).

Antihypertensive Agents↗
PubMed2006

Methylenetetrahydrofolate reductase polymorphisms and homocysteine-lowering effect of vitamin therapy in Singaporean stroke patients.

BACKGROUND AND PURPOSE: Increased plasma total homocysteine (tHcy) levels are a risk factor for stroke and can be reduced with vitamin therapy. However, data on the tHcy-lowering effects of vitamins are limited largely to white populations. Thus, we aimed to determine in Singaporean patients with recent stroke: (1) the efficacy of vitamin therapy (folic acid, vitamin B12, and B6) on lowering tHcy, and (2) whether efficacy is modified by Methylenetetrahydrofolate reductase (MTHFR) gene polymorphism(s). METHODS: A total of 443 eligible patients were recruited after presenting with ischemic stroke within the past 7 months. Patients were randomized to receive either placebo or vitamins. Fasting blood samples collected at baseline and at 1 year were assayed for levels of plasma tHcy. Patients were genotyped for MTHFR C677T and A1298C polymorphisms. RESULTS: Mean baseline tHcy was similar in the 2 groups (placebo 13.7 micromol/L; vitamins 14.0 micromol/L; P=0.70). At 1 year, mean tHcy was 14.5 micromol/L in the placebo group compared with 10.7 micromol/L in the vitamin group (difference 3.8 micromol/L; 95% CI, 2.8 to 4.8 micromol/L; P<0.0001). MTHFR C677T genotype was an independent determinant of tHcy levels at baseline (P=0.005), but A1298C was not (P=0.08). Neither polymorphism significantly influenced the effect of vitamin therapy on tHcy at 1 year. The magnitude of the reduction in tHcy levels at 1 year with vitamin therapy was similar, irrespective of MTHFR genotypes. CONCLUSIONS: Vitamin therapy reduces mean tHcy levels by 3.8 micromol/L in the Singaporean stroke population studied. MTHFR C677T but not A1298C is independently associated with tHcy levels at baseline, and neither impacts the tHcy-lowering effect of vitamins used in this study.

Aged↗
PubMed2006

National Stroke Association guidelines for the management of transient ischemic attacks.

OBJECTIVE: Transient ischemic attacks are common and important harbingers of subsequent stroke. Management varies widely, and most published guidelines have not been updated in several years. We sought to create comprehensive, unbiased, evidence-based guidelines for the management of patients with transient ischemic attacks. METHODS: Fifteen expert panelists were selected based on objective criteria, using publication metrics that predicted nomination by practitioners in the field. Prior published guidelines were identified through systematic review, and recommendations derived from them were rated independently for quality by the experts. Highest quality recommendations were selected and subsequently edited by the panelists using a modified Delphi approach with multiple iterations of questionnaires to reach consensus on new changes. Experts were provided systematic reviews of recent clinical studies and were asked to justify wording changes based on new evidence and to rate the final recommendations based on level of evidence and quality. No expert was allowed to contribute to recommendations on a topic for which there could be any perception of a conflict of interest. RESULTS: Of 257 guidelines documents identified by systematic review, 13 documents containing 137 recommendations met all entry criteria. Six iterations of questionnaires were required to reach consensus on wording of 53 final recommendations. Final recommendations covered initial management, evaluation, medical treatment, surgical treatment, and risk factor management. INTERPRETATION: The final recommendations on the care of patients with transient ischemic attacks emphasize the importance of urgent evaluation and treatment. The novel approach used to develop these guidelines is feasible, allows for rapid updating, and may reduce bias.

Health Planning Guidelines↗
PubMed2006

Behavioural intervention for dysphagia in acute stroke: a randomised controlled trial.

BACKGROUND: Swallowing dysfunction after stroke is common, but there is little reliable evidence for how the disorder should be managed. This study compared standard low-intensity and high-intensity behavioural interventions with usual care for dysphagia. METHODS: 306 patients with clinical dysphagia admitted to hospital with acute stroke were randomly assigned to receive usual care (n=102), prescribed by the attending physician; standard low-intensity intervention (n=102), comprising swallowing compensation strategies and diet prescription three times weekly for up to a month; or standard high-intensity intervention and dietary prescription (n=102), at least daily for up to a month. The primary outcome measure was survival free of an abnormal diet at 6 months. Analysis was done by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00257764. FINDINGS: 60 patients died and three patients were lost to follow up before the 6-month analysis. Of patients randomly allocated usual care, 56% (57/102) survived at 6 months free of an abnormal diet compared with 67% (136/204) allocated standard swallowing therapy (relative risk 1.19, 95% CI 0.98-1.45). Standard swallowing therapy was associated with a non-significant trend toward a reduction in death (0.80, 0.5-1.3), institutionalisation (0.69, 0.4-1.1), and dependency (1.05, 0.8-1.3); a significant reduction in swallowing-related medical complications (0.73, 0.6-0.9), chest infection (0.56, 0.4-0.8), and death or institutionalisation (0.73, 0.55-0.97); and a significant rise in the proportion of patients regaining swallowing function (1.41, 1.03-1.94) by 6 months. Compared with usual care and low-intensity therapy, high-intensity therapy was associated with an increased proportion of patients who returned to a normal diet (p=0.04) and recovered swallowing (p=0.02) by 6 months. INTERPRETATION: These data show a consistent trend towards more favourable outcomes in dysphagic stroke patients who are assigned a standard programme of early behavioural swallowing intervention, including active therapeutic approaches and dietary modification.

Aged↗
PubMed2006

Is plasma homocysteine a modifiable risk factor for stroke?

Increased levels of plasma total homocysteine (tHcy) can be caused by genetic mutations, vitamin deficiencies, renal and other diseases, and numerous drugs. Raised tHcy also correlate with increasing age, and are associated with laboratory evidence of atherogenesis (e.g. endothelial dysfunction) and thrombosis, and with epidemiological evidence of an increased risk of atherothrombotic vascular disease, including ischemic stroke. The association between raised tHcy and increased risk of ischemic stroke is independent of other known vascular risk factors and is biologically plausible; however, randomized controlled trials have not revealed a causal relationship. The recently published Vitamins In Stroke Prevention (VISP) trial identified no significant reduction in the relative risk of stroke by lowering tHcy with B-vitamin therapy among 3,680 patients with recent ischemic stroke. It did not, however, reliably exclude a modest but important reduction of up to 20% in relative risk of stroke. Currently, there is insufficient evidence to confirm that homocysteine is a modifiable causal risk factor for stroke, or to recommend routine screening for, or treatment of, raised tHcy concentrations with folic acid and other vitamins, to prevent ischemic stroke.

Clinical Trials as Topic↗
PubMed2006

The tissue factor pathway in ischemic stroke.

To explore the role of the the tissue factor (TF) pathway in ischemic stroke. We measured blood concentrations of markers of the TF pathway [TF antigen, free tissue factor pathway inhibitor antigen (TFPIf) and activity (TFPIac), and activated factor VII (FVIIa)] within 7 days (acute phase) and after 3-6 months (convalescence) in 150 patients with first-ever ischemic stroke and 150 community controls. During the acute phase, TF antigen and TFPIf were not significantly altered but TFPIac was increased (mean 1.27 versus 1.13 U/ml, P = 0.04) and FVIIa was decreased in cases compared with controls (mean 43.3 versus 57.9 mU/ml, P = 0.0004). After adjusting for baseline differences between cases and controls, increasing quartiles of TFPIf were independently associated with reduced odds of stroke, and reducing quartiles of FVIIa and increasing quartiles of TFPIac with increased odds of stroke. During the convalescent phase, FVIIa and TFPIac returned to normal but TF antigen and TFPIf were significantly decreased compared with controls [median TF antigen, 110 (follow-up) versus 155 pg/ml (controls), P = 0.0008; median TFPIf, 15.5 (follow-up) versus 23.3 ng/ml (controls), P = 0.002]. Alterations of blood concentrations of TF pathway markers are common in patients with acute ischemic stroke. The mechanisms are unclear but may relate to enhanced formation of TF-FVIIa complexes and upregulation and release of TFPI during the acute phase, and ongoing consumption of TF antigen and TFPIf during the chronic phase as the atherosclerotic plaque heals.

Aged↗
PubMed2006

Preventing depression after stroke: Results from a randomized placebo-controlled trial.

OBJECTIVE: We designed this study to determine whether the daily treatment of nondepressed acute stroke patients with sertraline reduced the incidence of depression at follow-up. METHOD: 111 patients with recent stroke (< 2 weeks; International Classification of Diseases, Tenth Revision criteria) were randomly assigned to treatment with placebo (N = 56) and sertraline (N = 55, 50 mg once daily) in this double-blind, placebo-controlled 24-week clinical trial. Subjects were recruited from the 2 largest teaching hospitals of Western Australia between June 2002 and June 2004. The primary endpoint of interest was development of clinically significant depressive symptoms as assessed by a Hospital Anxiety and Depression Scale-depression subscale score of 8 or above, or as diagnosed by the treating physician during 24 weeks. RESULTS: There was no significant difference in the incidence of depressive symptoms during 24 weeks of treatment (16.7% [8/48] sertraline vs. 21.6% [11/51] placebo, rate ratio = 0.8, 95% CI = 0.3 to 2.1, p = .590). The trial medication was discontinued by 51.8% (29/56) of patients assigned placebo and 47.3% (26/55) assigned sertraline (p = .634), most often because of perceived side effects or because the treating physician introduced an antidepressant medication. CONCLUSIONS: Twenty-four-week treatment with 50 mg of sertraline once daily initiated within 2 weeks of onset of acute stroke is not a significantly more effective strategy to prevent 6-month depression than usual care plus placebo among nondepressed stroke patients. New pharmacologic and nonpharmacologic strategies need to be developed to reduce the health and financial burden associated with depression after stroke.

Adult↗
PubMed2005

Efficacy of B vitamins in lowering homocysteine in older men: maximal effects for those with B12 deficiency and hyperhomocysteinemia.

BACKGROUND AND PURPOSE: A higher plasma concentration of total homocysteine (tHcy) is associated with a greater risk of cardiovascular events. Previous studies, largely in younger individuals, have shown that B vitamins lowered tHcy by substantial amounts and that this effect is greater in people with higher tHcy and lower folate levels. METHODS: We undertook a 2-year, double-blind, placebo-controlled, randomized trial in 299 men aged > or =75 years, comparing treatment with a daily tablet containing 2 mg of folate, 25 mg of B6, and 400 microg of B12 or placebo. The study groups were balanced regarding age (mean+/-SD, 78.9+/-2.8 years), B vitamins, and tHcy at baseline. RESULTS: Among the 13% with B12 deficiency, the difference in mean changes in treatment and control groups for tHcy was 6.74 micromol/L (95% CI, 3.94 to 9.55 micromol/L) compared with 2.88 micromol/L (95% CI, 0.07 to 5.69 micromol/L) for all others. Among the 20% with hyperhomocysteinaemia, the difference between mean changes in treatment and control groups for men with high plasma tHcy compared with the rest of the group was 2.8 micromol/L (95% CI, 0.6 to 4.9 micromol/L). Baseline vitamin B12, serum folate, and tHcy were significantly associated with changes in plasma tHcy at follow-up (r=0.252, r=0.522, and r=-0.903, respectively; P=0.003, <0.001, and <0.001, respectively) in the vitamin group. CONCLUSIONS: The tHcy-lowering effect of B vitamins was maximal in those who had low B12 or high tHcy levels. Community-dwelling older men, who are likely to be deficient in B12 or have hyperhomocysteinemia, may be most likely to benefit from treatment with B vitamins.

Aged↗