Risk of cerebrovascular accident after a first diagnosis of atrial fibrillation

BACKGROUND: Atrial fibrillation is the most common cardiac arrhythmia and a major risk factor for cerebrovascular accident, including ischemic stroke and transient ischemic attack. HYPOTHESIS: Ischemic cerebrovascular accident is associated with increasing age and cardiovascular and cerebrovascular disease in primary care patients with atrial fibrillation. METHODS: Using the U.K. General Practice Research Database, we identified patients with chronic atrial fibrillation who were alive 1 month after initial diagnosis (n = 906). Potential cases of cerebrovascular accident were identified and confirmed by the primary care physician. The incidence of cerebrovascular accident was calculated. A nested case-control analysis was performed to identify factors associated with cerebrovascular accident among patients with chronic atrial fibrillation. RESULTS: During a mean follow-up period of 1.8 years (range: 0-3.9 years), 60 patients with atrial fibrillation were diagnosed with a new cerebrovascular accident (22 cases with transient ischemic attack and 38 with ischemic stroke). The incidence of new cerebrovascular accident was 3.6 per 100 patient-years (95% confidence interval [CI]: 2.8-4.6). Increased age (odds ratios [OR] compared with age 40-69 years: 3.5 [95% CI: 1.2-10.5] for age 70-79 years and 4.9 [95% CI: 1.6-15.0] for age > or = 80 years), prior cerebrovascular event (OR: 3.4; 95% CI: 1.9-6.1) and diabetes (OR: 2.2; 95% CI: 1.0-4.9) were identified as risk factors for a new cerebrovascular accident. CONCLUSIONS: Among patients with atrial fibrillation, risk factors for a new ischemic cerebrovascular accident include previous ischemic stroke or transient ischemic attack, comorbid diabetes, and increasing age.     

Lower contribution of factor V Leiden or G202104 mutations to ischemic stroke in patients with clinical risk factors: pair-matched case-control study.

It was suggested that factor V Leiden and prothrombin G20210A mutations increase the risk of ischemic stroke only in combination with clinical risk factors of arterial ischemic disease. In these studies the controls were derived from the general population, with fewer clinical risk factors, which might have produced biased results. The factor V Leiden and prothrombin G20210A mutations were examined by polymerase chain reaction technique in 120 ischemic stroke patients and 120 controls younger than 65 years of age. Each patient had his own control, tightly matched in clinical risk factors. The prevalences of factor V Leiden and prothrombin G20210A mutations in patients were 8.3% (P = 0.02) and 7.5% (P = 0.04), respectively, and 2.5% for controls for both mutations. All carriers were single heterozygotes. In patients, but not in controls, the carriers of either mutation were mostly women and with fewer clinical risk factors for arterial ischemic events. In particular, considering both mutations as a single coagulation deficit, their presence increased the likelihood of ischemic stroke (odds ratio [OR] = 3.6; 95% confidence interval [CI] 1.4-9.3), especially among women (OR = 4.6; 95% CI: 1.2-17.8), normotensive persons (OR = 9.2; 95% CI: 1.1-17.8) and those having normal cholesterol (OR = 5.9; 95% CI: 1.6-21.2) and triglyceride serum concentrations (OR = 4.3; 95% CI: 1.5-12.8). In the studied sample of adult North Mediterranean population younger than 65 years the prevalences of factor V Leiden and prothrombin G20210A mutations were greater in patients with ischemic stroke than in matched controls. Unlike in studies with unmatched controls, we observed an apparently negative interaction of these mutations with clinical risk factors.     

Tenecteplase versus alteplase for management of acute ischemic stroke: a pairwise and network meta-analysis of randomized clinical trials

Tenecteplase is a genetically mutated variant of alteplase with superior pharmacodynamic and pharmacokinetic properties. However, its efficacy and safety in acute ischemic strokes are limited. Hence, we conducted a study to evaluate the efficacy and safety of tenecteplase compared with alteplase in acute ischemic stroke. Electronic databases were searched for randomized clinical trials (RCTs) comparing tenecteplase with alteplase in acute ischemic stroke patients eligible for thrombolysis. We evaluated various efficacy and safety outcomes using random-effects models for both pairwise and Bayesian network meta-analyses along with meta-regression analyses. We included 5 RCTs with a total of 1585 patients. Compared with alteplase, tenecteplase treatment was associated with significantly greater complete recanalization (odd ratio [OR] 2.01; 95% confidence interval [CI] 1.04–3.87; p?=?0.04) and early neurological improvement (OR 1.43; 95% CI 1.01–2.03; p?=?0.05). There were no differences between the two thrombolytics in terms of excellent recovery (modified Rankin Scale [mRS] 0–1; OR 1.17; 95% CI 0.95–1.44; p?=?0.13), functional independence (mRS 0–2; OR 1.24; 95% CI 0.78–1.98), poor recovery (mRS 4–6; OR 0.78; 95% CI 0.49–1.25; p?=?0.31), complete/partial recanalization (OR 1.51; 95% CI 0.70–3.26; p?=?0.30), any intracerebral hemorrhage (OR 0.81; 95% CI 0.56–1.17; p?=?0.26), symptomatic intracerebral hemorrhage (OR 0.98; 95% CI 0.52–1.83; p?=?0.94), or mortality (OR 0.83; 95% CI 0.54–1.26; p?=?0.38). In network meta-analysis, there were better efficacy and imaging-based outcomes with tenecteplase 0.25 mg/kg without increased risk of safety outcomes. Our results demonstrate that in acute ischemic stroke, thrombolysis with tenecteplase is at least as effective and safe as alteplase.     

Lipoprotein-associated phospholipase A2, hormone use, and the risk of ischemic stroke in postmenopausal women

Few studies have investigated the role of elevated lipoprotein-associated phospholipase A2 (Lp-PLA(2)) with stroke risk, and those that have are based on small numbers of strokes. No study has evaluated the effect of hormone therapy use on the association of Lp-PLA(2) and stroke. We assessed the relationship between Lp-PLA(2) and the risk of incident ischemic stroke in 929 stroke patients and 935 control subjects in the Hormones and Biomarkers Predicting Stroke Study, a nested case-control study from the Women's Health Initiative Observational Study. Mean (SD) levels of Lp-PLA(2) were significantly higher among case subjects (309.0 [97.1]) than control subjects (296.3 [87.3]; P<0.01). Odds ratio for ischemic stroke for the highest quartile of Lp-PLA(2), compared with lowest, controlling for multiple covariates, was 1.08 (95% CI: 0.75 to 1.55). However, among 1137 nonusers of hormone therapy at baseline, the corresponding odds ratio was 1.55 (95% CI: 1.05 to 2.28),whereas there was no significant association among 737 hormone users (odds ratio: 0.70; 95% CI: 0.42 to 1.17; P for interaction=0.055). Moreover, among nonhormone users, women with high C-reactive protein and high Lp-PLA2 had more than twice the risk of stroke (odds ratio: 2.26; 95% CI: 1.55 to 3.35) compared with women low levels in both biomarkers. Furthermore, different stroke cases were identified as high risk by Lp-PLA(2) rather than by C-reactive protein. Lp-PLA(2) was associated with incident ischemic stroke independently of C-reactive protein and traditional cardiovascular risk factors among nonusers of hormone therapy with highest risk in those who had both high C-reactive protein and high Lp-PLA(2).     

Inflammatory predictors of mortality in the Scandinavian Simvastatin Survival Study

BACKGROUND AND HYPOTHESIS: The predictive value of specific markers of infection and autoimmunity for coronary events, such as the effects of statins on inflammation, is still controversial. METHODS: A case-control design was used to compare C-reactive protein (CRP) levels, seropositivity for Chlamydia pneumoniae and Helicobacter pylori, and anti-oxidized low-density lipoprotein (oxLDL) antibody levels in prerandomization blood samples from 129 participants in the Scandinavian Simvastatin Survival Study who died (cases), and from 129 matched participants who were alive during 5-year follow-up (controls). RESULTS: Patients with CRP levels in the highest quartile had an increased risk of death compared with those in the first through third quartile (odds ratio [OR] = 2.51, 95% confidence interval [CI] 1.3-4.8). Seropositivity for Chlamydia pneumoniae or Helicobacter pylori and anti-oxLDL antibody levels were similar in cases and controls (p = NS). At a 4-month control, simvastatin reduced CRP levels (p = 0.009) while placebo did not (p = NS). However, the risk of death associated with high baseline CRP levels was similar in patients randomized to placebo (OR = 2.36, 95% CI 1.06-5.26) or simvastatin (OR = 3.13, 95% CI 1.06-9.21). CONCLUSIONS: Elevated CRP levels, but not seropositivity for Chlamydia pneumoniae or Helicobacter pylori, nor levels of anti-oxLDL antibodies, predict the risk of death in patients with stable ischemic heart disease. Simvastatin treatment reduces CRP levels, but without affecting the increased risk conferred by higher CRP levels at baseline.     

Serum myeloperoxidase levels are associated with the future risk of coronary artery disease in apparently healthy individuals: the EPIC-Norfolk Prospective Population Study.

OBJECTIVES: We evaluated whether serum myeloperoxidase (MPO) levels are associated with the risk of future development of coronary artery disease (CAD) in apparently healthy individuals. BACKGROUND: An enzyme of the innate immune system, MPO exhibits a wide array of proatherogenic effects. These include induction of oxidative damage to low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol and promotion of plaque vulnerability. Recent studies revealed that MPO independently predicts adverse outcomes in patients with chest pain or suspected acute coronary syndrome. METHODS: Myeloperoxidase was measured in baseline samples of a case-control study nested in the prospective EPIC (European Prospective Investigation into Cancer and Nutrition)-Norfolk population study. Case subjects (n = 1,138) were apparently healthy men and women who developed CAD during 8-year follow-up. Control subjects (n = 2,237), matched for age, gender, and enrollment time, remained free of CAD. RESULTS: The MPO levels were significantly higher in case subjects than in control subjects and correlated with C-reactive protein (CRP) (rho = 0.25; p < 0.001) and white blood cell count (rho = 0.33; p < 0.001). Risk of future CAD increased in consecutive quartiles of MPO concentration, with an odds ratio (OR) of 1.49 in the top versus bottom quartile (95% confidence interval [CI] 1.20 to 1.84; p < 0.001). After adjustment for traditional risk factors, the OR in the top quartile remained significant at 1.36 (95% CI 1.07 to 1.73). Elevated MPO levels (>728 pmol/l) similarly predicted increased risk of future CAD among participants with either LDL-cholesterol <130 mg/dl, HDL-cholesterol >50 mg/dl, or CRP <2.0 mg/l (OR 1.52 [95% CI 1.21 to 1.91], 1.59 [95% CI 1.24 to 2.05], and 1.42 [95% CI 1.14 to 1.77)], respectively). CONCLUSION: Elevated MPO levels predict future risk of CAD in apparently healthy individuals. This study suggests that inflammatory activation precedes the onset of overt CAD by many years.     

Cardiovascular, rheumatologic, and pharmacologic predictors of stroke in patients with rheumatoid arthritis: a nested, case-control study

OBJECTIVE: To determine the risk of stroke in patients with rheumatoid arthritis (RA) and risk factors associated with stroke. METHODS: We performed nested case-control analyses within a longitudinal databank, matching up to 20 controls for age, sex, and time of cohort entry to each patient with stroke. Conditional logistic regression was performed as an estimate of the relative risk of stroke in RA patients compared with those with noninflammatory rheumatic disorders, and to examine severity and anti-tumor necrosis factor (anti-TNF) treatment effects in RA. RESULTS: We identified 269 patients with first-ever all-category strokes and 67 with ischemic stroke, including 41 in RA patients. The odds ratio (OR) for the risk of all-category stroke in RA was 1.64 (95% confidence interval [95% CI] 1.16-2.30, P = 0.005), and for ischemic stroke was 2.66 (95% CI 1.24-5.70, P = 0.012). Ischemic stroke was predicted by hypertension, myocardial infarction, low-dose aspirin, comorbidity score, Health Assessment Questionnaire score, and presence of total joint replacement, but not by diabetes, smoking, exercise, or body mass index. Adjusted for cardiovascular and RA risk factors, ischemic stroke was associated with rofecoxib (P = 0.060, OR 2.27 [95% CI 0.97-5.28]), and possibly with corticosteroid use. Anti-TNF therapy was not associated with ischemic stroke (P = 0.584, OR 0.80 [95% CI 0.34-1.82]). CONCLUSION: RA is associated with increased risk of stroke, particularly ischemic stroke. Stroke is predicted by RA severity, certain cardiovascular risk factors, and comorbidity. Except for rofecoxib, RA treatment does not appear to be associated with stroke, although the effect of corticosteroids remains uncertain.     

Relation of increased leptin concentrations to history of myocardial infarction and stroke in the United States population

Leptin, an adipose tissue-derived hormone, has been linked to cardiovascular outcomes; however, data are limited in the United States population, especially women. To assess the association between leptin concentrations and history of myocardial infarction (MI) and stroke independently of traditional cardiovascular risk factors, we analyzed data from 6,239 subjects (mean age 47 years; 3,336 women) with measurements of serum leptin and full assessment of cardiovascular risk factors from the National Health and Nutrition Examination Survey (NHANES) III. Logistic regression was used to estimate the cross-sectional association of leptin concentrations (highest quartile versus lowest quartile) and history of MI, stroke, and the composite end point of MI or stroke (MI/stroke). Gender-specific models of leptin were adjusted for age, race, dyslipidemia, hypertension, diabetes, smoking, and obesity status. There were 212 men with MI/stroke (5.4%), 154 with MI (4.1%), and 82 with stroke (1.7%). There were 135 women with MI/stroke (2.6%), 74 with MI (1.5%), and 78 with stroke (1.4%). In multivariate analysis, high leptin level was significantly and independently associated with MI/stroke in men (odds ratio [OR] 2.41, 95% confidence interval [CI] 1.20 to 4.93) and women (OR 4.26, 95% CI 1.75 to 10.73); with MI in men (OR 3.16, 95% CI 1.40 to 7.37) and women (OR 3.96, 95% CI 1.29 to 12.72), and with stroke in women (OR 3.20, 95% CI 1.04 to 10.54) but not in men (OR 1.37, 95% CI 0.38 to 3.88). In conclusion, in the United States population, increased leptin concentrations are significantly associated with MI/stroke in men and women independently of traditional cardiovascular risk factors and obesity status.     

Monitored atrial fibrillation duration predicts arterial embolic events in patients suffering from bradycardia and atrial fibrillation implanted with antitachycardia pacemakers.

OBJECTIVES: The aim of our study was to evaluate arterial embolism (AE) occurrence rates and predictors in patients suffering from bradycardia and wearing a pacemaker with antitachycardia pacing therapies. BACKGROUND: Atrial fibrillation (AF) is associated with a high incidence of AE. METHODS: A total of 725 patients (360 men, age 71 +/- 11 years) were implanted with a DDDRP pacemaker (Medtronic AT500, Medtronic Inc., Minneapolis, Minnesota). At baseline 225 (31.0%) patients received antiplatelet therapy and 264 (36.4%) patients received anticoagulation agents. RESULTS: Over a median 22-month follow-up (25th to 75th interquartile range 16 to 30 months), AE occurred in 14 (1.9%) patients: 7 patients suffered a nonfatal ischemic stroke (0.6% per year), 4 patients had transient ischemic attack (0.34% per year), and 3 patients had embolic complications. Among baseline patients' characteristics, multivariate logistic analysis showed that embolic events are independently associated to ischemic heart disease (7.0 odds ratio [OR], 95% confidence interval [CI] 2.3 to 21.3, p = 0.001), prior embolic event (7.3 OR, 95% CI 1.2 to 43.9, p = 0.029), diabetes (5.0 OR, 95% CI 1.2 to 15.7, p = 0.032), and hypertension (4.1 OR, 95% CI 1.1 to 15.6, p = 0.036). The risk of embolism, adjusted for known risk factors, was 3.1 times increased (95% CI 1.1 to 10.5, p = 0.044) in patients with device-detected atrial fibrillation episodes longer than one day during follow-up. CONCLUSIONS: In a cohort of patients with bradycardia and AF, arterial embolism was common in patients with ischemic cardiopathy, hypertension, diabetes mellitus, and in patients with known stroke risk factors. Atrial fibrillation occurrences longer than one day were independently associated with embolic events.     

Hyperglycemia correlates with outcomes in patients receiving total parenteral nutrition

BACKGROUND: Hyperglycemia is associated with higher mortality rates after myocardial infarction, stroke, and in critically ill patients. This study was made to determine the associations between hyperglycemia and adverse outcomes in patients receiving total parenteral nutrition (TPN). METHODS: A retrospective cohort study included total 457 patients (age, 66.4 +/- 16.3 years) receiving TPN in 2004. The patients were divided by mean glucose level into quartiles: quartile 1 (<114 mg/dL, Q1), quartile 2 (114 to 137 mg/dL, Q2), quartile 3 (137 to 180 mg/dL, Q3), and quartile 4 (>180 mg/dL, Q4). A logistic regression analysis was performed to determine whether the degree of hyperglycemia was associated with the adverse outcomes. RESULTS: The odds ratio of death was significantly increased in quartile 2 (OR, 2.1 [95% CI: 1.1 to 4.0]) (P = 0.02), quartile 3 (OR, 2.3 [95% CI: 1.2 to 4.5]) (P = 0.01), and quartile 4 (OR, 5.0 [95% CI: 2.4 to 10.6]) (P < 0.01) as compared with quartile 1. Each 10-mg/dL increase in mean blood glucose level was associated with an increased risk factor of infection (OR, 1.09 [95% CI: 1.05 to 1.13]) (P < 0.01), cardiac complications (OR, 1.10 [95% CI: 1.03 to 1.17]) (P < 0.01), acute renal failure (OR, 1.07 [95% CI: 1.03 to 1.11]) (P < 0.01), and respiratory failure (OR, 1.08 [95% CI: 1.02 to 1.14]) (P < 0.01). The risk of adverse outcomes increased with hyperglycemia, independent of age, sex, body weight, prior diagnosis of diabetes, ICU stay, insulin therapy, blood sugar readings before TPN treatment, and frequency of blood sugar measurements. CONCLUSIONS: Hyperglycemia in patients receiving TPN correlates with morbidities and mortality. A prospective, randomized, controlled study instituting aggressive hyperglycemic control is required to determine whether the control of blood glucose can improve outcomes in patients receiving TPN.     

Significance of elevated blood pressure and its management on the short-term outcome of patients with acute ischemic stroke

BACKGROUND: The objectives of this study were to characterize blood pressure (BP) in acute ischemic stroke and to determine its relationship with short-term functional outcome. METHODS: We examined 24-h BP recordings in 434 patients with ischemic stroke (lacunar stroke [LS], n = 205; non-lacunar stroke [NLS], n = 229) and in 178 normotensive subjects. Stroke severity was evaluated by the National Institutes of Health Stroke Scale (NIHSS). Patients found to be hypertensive on BP recordings on day 1 were given captopril or amlodipine. The primary outcome was both moderate-to-severe disability (Rankin scale scores 4 to 6) on day 7 or death during hospital stay. RESULTS: Patients with LS and NLS had significantly higher systolic BP (SBP) and diastolic BP levels than control subjects. On day 1, patients with NLS showed significantly higher NIHSS scores, SBP, and heart rate (HR) levels than LS patients. In the multivariate analysis, combined death or dependency was associated with NIHSS score (odds ratio [OR] = 1.08 per 1-point increase, 95% confidence interval [CI] = 1.04 to 1.13), 24-h SBP >160 mm Hg (OR = 2.35, 95% CI = 1.10 to 5.52), and plasma glucose levels >125 mg/dL on admission (OR = 1.88, 95% CI =1.03 to 3.57), whereas a decrease in SBP on day 7 (OR = 0.46, 95% CI = 0.24 to 0.88) was associated with better short-term outcome. CONCLUSIONS: At presentation, NLS patients showed higher BP levels than LS patients. Moderate reductions in BP during the first week after admission were associated with short-term functional improvement in patients with acute ischemic stroke.     

Insulin-like growth factor (IGF) I, -II, and IGF binding protein-3 and risk of ischemic stroke

BACKGROUND: Low IGF-I levels may be associated with the development of stroke; however, prospective data appear to be unavailable. METHODS: This was a nested case-control study within a Danish follow-up study, including 57,053 men and women. Baseline data included circulating IGF-I, IGF-II, and IGF binding protein (IGFBP)-3 concentrations as well as lifestyle factors and medical history. We identified 254 cases with incident ischemic stroke and 254 gender- and age-matched controls. RESULTS: Participants in the bottom quartiles of IGF-I and IGFBP-3 levels (median concentrations, 72 and 2937 ng/ml, respectively) were at increased risk of ischemic stroke, e.g. adjusted odds ratios (ORs) of 2.06 [95% confidence interval (CI), 1.05-4.03] and 2.29 (95% CI, 1.17-4.49), respectively, when compared with participants in the top quartiles (median concentrations, 125 and 4835 ng/ml, respectively). A negative, although weaker, association was also found for IGF-II (adjusted OR 1.44, 95% CI 0.79-2.64) when comparing the bottom quartile with the top quartile. No substantial associations were seen for IGF-I and IGF-II when also adjusting for IGFBP-3; adjusting IGFBP-3 for IGF-I and -II had only a minor impact on the risk estimates. CONCLUSION: These findings give some support to the hypothesis that the IGF axis is involved in the pathogenesis of ischemic stroke.     

How do anticoagulated atrial fibrillation patients who suffer ischemic stroke or spontaneous intracerebral hemorrhage differ?

Background

Atrial fibrillation (AF) increases risk of ischemic stroke, and oral anticoagulation (OAC) increases risk of intracerebral hemorrhage (ICH). This study aimed to compare OAC‐treated AF patients with an ischemic stroke/transient ischemic attack (TIA) or spontaneous ICH as their first lifetime cerebrovascular event, especially focusing on patients with therapeutic international normalized ratio (INR).

Hypothesis

We assumed that in AF patients suffering ischemic stroke/TIA or ICH, patient characteristics could be different in patients with therapeutic INR than in patients with warfarin.

Methods

FibStroke is a multicenter, retrospective registry collating details of AF patients with ischemic stroke/TIA or intracranial hemorrhage in 2003–2012. This substudy included AF patients on OAC with first lifetime ischemic stroke/TIA or spontaneous ICH.

Results

A total of 1457 patients with 1290 ischemic strokes/TIAs and 167 ICHs were identified. Of these, 553 (42.9%) strokes/TIAs and 96 (57.5%) ICHs occurred in patients with INR within therapeutic range. During OAC with therapeutic INR, congestive heart failure (odds ratio [OR]: 2.33, 95% confidence interval [CI]: 1.18–4.58) and hypercholesterolemia (OR: 2.52, 95% CI: 1.51–4.19) were more common in patients with ischemic stroke/TIA, whereas a history of bleeding (OR: 0.30, 95% CI: 0.11–0.82) was less common when compared with patients with ICH. In the whole cohort, renal impairment (OR: 1.86, 95% CI: 1.23–2.80) and mechanical valve prosthesis (OR: 4.41, 95% CI: 1.32–14.7) were overrepresented in patients with stroke/TIA, whereas aspirin use (OR: 0.52, 95% CI: 0.30–0.91) and high INR (OR: 0.40, 95% CI: 0.33–0.48) were overrepresented in patients with ICH.

Conclusions

In anticoagulated AF patients with therapeutic INR and first lifetime cerebrovascular event, congestive heart failure and hypercholesterolemia were associated with ischemic stroke/TIA and history of bleeding with ICH.     

亚甲基四氢叶酸还原酶基因rs4846049 G/T多态性与中国汉族人群缺血性卒中的相关性

目的：探讨亚甲基四氢叶酸还原酶(methylenetetrahydrofolatereductase, MTHFR)基因3'-非翻译区rs4846049 G/T多态性与中国汉族人群缺血性卒中发病风险的相关性。方法采用病例对照研究设计,选取396例缺血性卒中患者和378名健康体检者(对照组),病例组大动脉粥样硬化和小动脉闭塞型分别为268例和128例。采用聚合酶链反应-限制性片段长度多态性和直接测序法检测MTHFR 基因rs4846049 G/T多态性。结果以GG基因型为参照,TT基因型使缺血性卒中发病风险显著增高[优势比(odds ratio, OR)2．87,95%可信区间(confidence interval, CI)1．43~5．76;P=0．003];与G 等位基因比较,T 等位基因使发病风险显著增高( OR 1．62,95% CI 1．28~2．06;P<0．001)。亚组分析显示, rs4846049 G/T 多态性可显著增高 LAA 和 SAO 亚型卒中的发病风险(P均<0．05)。结论 MTHFR基因rs4846049 G/T多态性可能与中国汉族人群缺血性卒中易感性增高有关,T等位基因可能是中国汉族人群缺血性卒中的遗传危险因素。     

Body mass index, waist circumference, and waist-hip ratio on the risk of total and type-specific stroke

BACKGROUND: Adiposity is an established risk factor for cardiovascular disease, but the relationship of adiposity with the risk of cerebrovascular disease is still to some extent unclear. METHODS: We prospectively investigated the association of different indicators of adiposity (body mass index [BMI] [calculated as weight in kilograms divided by height in meters squared], waist circumference, and waist-hip ratio) with total and type-specific stroke incidence among 49 996 Finnish participants who were aged 25 to 74 years and free of coronary heart disease and stroke at baseline. RESULTS: During a 19.5-year follow-up, 3228 people developed an incident stroke event (674 hemorrhagic and 2554 ischemic). Compared with normal-weight men (BMI, 18.5-24.9), the multivariate-adjusted (age, study year, smoking, physical activity, educational level, family history of stroke, and alcohol drinking) hazard ratios among lean (BMI, < 18.5), overweight (BMI, 25.0-29.9), and obese (BMI, > or = 30.0) men were 0.74 (95% confidence interval [CI], 0.18-2.96), 1.23 (95% CI, 1.10-1.37), and 1.59 (95% CI, 1.37-1.83) for total stroke, and 0.49 (95% CI, 0.07-3.50), 1.27 (95% CI, 1.12-1.44), and 1.70 (95% CI, 1.45-2.00) for ischemic stroke, respectively. Among women, the corresponding hazard ratios were 1.87 (95% CI, 1.12-3.14), 1.08 (95% CI, 0.95-1.22), and 1.30 (95% CI, 1.14-1.50) for total stroke, and 1.81 (95% CI, 0.97-3.41), 1.11 (95% CI, 0.96-1.28), and 1.41 (95% CI, 1.21-1.64) for ischemic stroke. Abdominal adiposity, defined as the highest quartile of waist circumference or waist-hip ratio, was associated with a greater risk of total and ischemic stroke in men but not in women. CONCLUSIONS: Body mass index was a risk factor for total and ischemic stroke in men and women. Abdominal adiposity was a risk factor for total and ischemic stroke only in men.     

血清脂蛋白(a)与缺血性卒中及其病因学亚型的相关性

目的 探讨血清脂蛋白(a)[lipoprotein(a),Lp(a)]水平与急性缺血性卒中及其病因学亚型的相关性.方法 回顾性纳入连续的急性缺血性卒中住院患者(病例组)以及年龄和性别相匹配的同期健康体检者(对照组).收集病例组和对照组人口统计学和基线临床资料以及空腹血糖、纤维蛋白原、高半胱氨酸、总胆固醇、三酰甘油、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、Lp(a)浓度.病例组根据TOAST病因学分型标准分为大动脉粥样硬化(large artery atherosclerosis,LAA)、小动脉闭塞(small artery occlusion,SAO)、心源性栓塞(cardioembolism,CE),并排除其他明确病因和病因不明的患者.对病例组和对照组人口统计学和基线临床资料进行比较,并采用多变量logistic回归分析明确血清Lp(a)与急性缺血性卒中及其病因学分型的相关性.结果 共纳入214例缺血性卒中组患者,其中LAA 97例(45.33%),SAO 64例(29.91%),CE 53例(24.77%);对照组118例.病例组高血压、糖尿病、高脂血症、心房颤动和饮酒的比例以及收缩压、舒张压、空腹血糖、总胆固醇、低密度脂蛋白胆固醇、Lp(a)、纤维蛋白原、高半胱氨酸水平与对照组存在统计学差异(P均<0.001).多变量logistic回归分析显示,校正年龄和性别后,Lp(a)是缺血性卒中的独立危险因素[优势比(odds ratio,OR)2.014,95%可信区间(confidence interval,CI)1.273~3.092;P=0.036];LAA的独立危险因素包括高血压(OR 3.353,95%CI 1.714~6.558;P<0.001)、收缩压(OR 2.786,95%CI 1.136~5.538;P=0.016)、高半胱氨酸(OR 1.108,95%CI 1.031~2.191;P=0.005)、总胆固醇(OR 2.169,95%CI 1.599~4.943;P<0.001)、低密度脂蛋白胆固醇(OR 2.782,95%CI 1.093~5.238;P=0.024)和Lp(a)(OR 3.072,95%CI 1.907~8.064;P=0.001),SAO的独立危险因素包括高血压(OR 7.042,95%CI 3.189~25.55;P<0.001)、糖尿病(OR 5.162,95%CI 2.372~11.23;P<0.001)、纤维蛋白原(OR 1.667,95%CI 1.434~2.025;P=0.045)和高半胱氨酸(OR 1.967,95%CI 1.859~1.995;P=0.036),CE的独立危险因素包括心房颤动(OR 13.340,95%CI 4.637~39.20;P<0.001)、纤维蛋白原(OR 2.365,95%CI 1.147~4.904;P=0.029)和Lp(a)(OR 1.656,95%CI 1.996~3.001;P=0.035).结论 Lp(a)是缺血性卒中的独立危险因素,可作为预测缺血性卒中发病风险的血清生物学标记物.不同卒中病因学亚型之间的独立危险因素存在差异,Lp(a)与LAA和CE独立相关,但与SAO无独立性相关性.     

胚胎型大脑后动脉与急性缺血性卒中患者梗死分布和卒中严重程度的相关性

目的 探讨胚胎型大脑后动脉(Fetal-type posterior cerebral artery, FTP)与急性缺血性卒中患者梗死分布和卒中严重程度的相关性.方法 回顾性纳入急性缺血性卒中患者.根据磁共振血管造影结果分为FTP组和非FTP组,前者进一步分为完全型FTP(complete FTP, cFTP)和部分型FTP(partial FTP, pFTP).根据弥散加权成像结果将梗死部位分为大脑前动脉(anterior cerebral artery, ACA)供血区、大脑中动脉(middle cerebral artery, MCA)供血区、大脑后动脉(posterior cerebral artery, PCA)供血区及椎基底动脉(vertebrobasilar artery, VBA)供血区.根据美国国立卫生研究院卒中量表(National Institutes of Health Stroke Scale, NIHSS)评价卒中严重程度,<8分定义为轻度卒中,≥8分定义为中重度卒中.多变量logistic回归分析确定FTP与梗死分布和卒中严重程度的相关性.结果 共纳入647例急性缺血性卒中患者,201例(31.1%)存在FTP,其中cFTP 162例(25.0%),pFTP 39例(6.0%).多变量logistic回归分析显示,cFTP和pFTP是MCA供血区梗死的独立危险因素[cFTP:优势比(odds ratio, OR)24.714,95%可信区间(confidence interval, CI)10.952~45.766,P<0.001;pFTP:OR 14.526,95% CI 6.832~25.931,P<0.001]和PCA供血区梗死的独立保护因素(cFTP:OR 0.214,95% CI 0.022~0.531,P<0.001;pFTP:OR 0.326,95% CI 0.018~0.739,P<0.001),同时也是急性缺血性卒中严重程度的独立危险因素(cFTP:OR 22.138,95% CI 12.492~64.067,P<0.001;cFTP:OR 19.510,95% CI 8.956~23.514,P<0.001).结论:cFTP和pFTP是MCA供血区梗死的独立危险因素和PCA供血区梗死的独立保护因素,同时也是中重度卒中的独立危险因素.FTP与急性缺血性卒中患者的梗死分布和卒中严重程度相关.     

血清可溶性CD40配体水平与缺血性卒中发病风险、严重程度和梗死体积的相关性

目的探讨血清可溶性CD40配体(soluble CD40 ligand,sCD40L)水平与缺血性卒中发病风险、严重程度和梗死体积的相关性.方法纳入连续住院的急性缺血性卒中患者作为病例组,健康体检者作为对照组.收集病例组和对照组人口统计学、血管危险因素和临床资料.采用酶联免疫吸附法测定血清sCD40L水平.缺血性卒中患者根据基线美国国立卫生研究院卒中量表(National Institutes of Health Stroke scale,NIHSS)评分分为轻度卒中组(＜8分)和中重度卒中组(≥8分),根据梗死体积中位数分为大梗死组和小梗死组.结果 共纳入106例急性缺血性卒中患者,其中男性59例(55.7％),女性47例(44.3％),平均年龄(71.31±11.27)岁;对照组86例,其中男性45例(52.3％),女性41例(47.7％),平均年龄(73.56 ±9.32)岁;大梗死组(≥1.8 cm3)41例(38.7％),小梗死组(＜1.8 cm3)65例(61.3％);轻度卒中69例(65.1％),中重度卒中37例(34.9％).缺血性卒中组基线血清sCD40L水平显著高于对照组[(5.61±1.68) mg/L对(3.56±1.32)mg/L;扣9.236,P＜0.01],缺血性卒中组入院14 d时血清sCD40L水平[(4.19±1.45)mg/L]较基线水平显著降低(P＜0.01),但仍然显著高于对照组(P＜0.01).多变量logistic回归分析显示,低密度脂蛋白胆固醇[优势比(odds ratio,OR)3.358,95％可信区间(confidence interval,CI)2.681 ～4.056;P ＜0.001]和血清sCD40L(OR5.103,95％ CI2.317 ～8.903;P ＜0.001)水平较高是缺血性卒中的独立危险因素;血清sCD40L水平较高(第4四分位数对第1四分位数,OR4.017,95％ CI1.608 ～ 10.037;P=0.003)、大动脉粥样硬化性卒中(OR2.321,95％ CI1.014 ～ 5.314;P=0.046)、皮质-皮质下梗死(OR 2.679,95％ CI1.111 ～6.460;P=0.028)和梗死灶体积较大(OR 3.216,95％ CI1.398～7.395;P=0.006)为中重度卒中的独立危险因素;血清sCD40L水平较高(第4四分位数对第1四分位数,OR 3.142,95％ CI1.274 ～7.745;P =0.013)、大动脉粥样硬化性卒中(OR 2.965,95％CI1.299 ～6.767;P=0.010)、皮质-皮质下梗死(OR4.750,95％ CI 1.909～11.818;P＜0.001)和基线NIHSS评分≥8分(OR 8.509,95％ CI3.432 ～21.094;P ＜0.001)为大梗死的独立危险因素.结论血清sCD40L 水平与缺血性卒中发病、梗死体积和严重程度密切相关.     

Association of Gut Microbiota-Dependent Metabolite Trimethylamine N-Oxide with First Ischemic Stroke

Aim: We aimed to investigate the relationship of trimethylamine N-oxide (TMAO) concentrations with ischemic stroke in a large-scale case-control study conducted among the hospital-based general population.Methods: We recruited 953 case-control sex- and age-matched pairs, and cases were confined to first acute ischemic stroke in this study. Fasting plasma TMAO was measured using high-performance liquid chromatography–tandem mass spectroscopy. Conditional logistic regression analysis was conducted to calculate odds ratios (OR) for the association of plasma TMAO with ischemic stroke.Results: We found that plasma TMAO concentrations in patients with ischemic stroke were significantly higher than that in the control group (median: 2.85 µmol/L vs. 2.33 µmol/L, P < 0.001). In multivariable conditional logistic regression models, higher plasma TMAO concentrations were associated with increased odds of ischemic stroke [fully adjusted OR for highest vs. lowest TMAO quartile: 1.81; 95% confidence interval (CI): 1.27, 2.59; P for trend < 0.001]. The multivariable-adjusted OR for ischemic stroke per 1 µmol/L increment of plasma TMAO was 1.05 (95% CI: 1.02, 1.08). Additionally, the positive association also persisted in subgroups stratified by age, sex, body mass index, smoking status, alcohol habits, history of diabetes, and history of hypertension.Conclusions: This study suggested a positive association between plasma TMAO and ischemic stroke. Further studies are required to explore the role of plasma TMAO concentrations in predicting stroke risk.     

Plasma N-terminal pro-B-type natriuretic peptide for prediction of death or nonfatal myocardial infarction following percutaneous coronary intervention

B-type natriuretic peptide (BNP) and the N-terminus of pro-BNP (NT-pro-BNP) have prognostic value in patients with heart failure and patients with acute coronary syndromes. Little is known about the prognostic value of baseline NT-pro-BNP alone or in combination with C-reactive protein (CRP) for clinical outcome after percutaneous coronary intervention (PCI). Within a single center registry of contemporaneous PCI, we investigated the prognostic value of baseline plasma NT-pro-BNP and CRP concentrations for the prediction of death or nonfatal myocardial infarction (MI) during 12 to 14 months of follow-up. Among 1,172 consecutive patients, the occurrence of death or MI increased significantly with baseline NT-pro-BNP before PCI (first quartile 0 of 294, second quartile 6 of 291 [2.1%], third quartile 4 of 294 [1.4%], fourth quartile 22 of 293 [7.5%)]; p <0.0001). NT-pro-BNP in the top quartile significantly predicted death (odds ratio [OR] 13.37, 95% confidence interval [CI] 4.50 to 40.38, p <0.0001) and was associated with nonfatal MI (OR 2.53, 95% CI 0.77 to 8.34, p = 0.22) An abnormal CRP was significantly associated with death (OR 3.47, 95% CI 1.26 to 9.54, p = 0.019). Stepwise multivariate logistic regression analysis identified age >65 years and NT-pro-BNP as independent significant predictors of death/MI (age OR 3.18, 95% CI 1.32 to 7.67, p = 0.01; NT-pro-BNP OR 4.57, 95% CI 2.07 to 10.10, p = 0.0001). Baseline NT-pro-BNP before PCI provides important, independent prognostic information for the occurrence of death or nonfatal MI during long-term follow-up.