Serum lipoprotein(a) levels and apolipoprotein(a) isoform size and risk for first-ever acute ischaemic nonembolic stroke in elderly individuals

In a population-based case-control study, we investigated the association of acute ischaemic stroke with lipoprotein(a) (Lp(a)) levels and apolipoprotein (Apo) (a) isoform size in subjects aged older than 70 years. A total of 163 patients with a first-ever-in-a-lifetime acute ischaemic/nonembolic stroke and 166 controls were included. Compared to controls, stroke patients exhibited higher Lp(a) concentrations (median value, 12.2 mg/dl versus 6.4 mg/dl, p < 0.001) and a higher frequency of small Apo(a) isoforms (44.2% versus 29.5%, p < 0.01). Multivariate logistic regression analysis showed a significant association of acute ischaemic stroke with Lp(a) levels [adjusted odds ratio (OR), 1.37, 95% CI (1.12-1.67); p = 0.002], and small Apo(a) isoform size [OR, 1.74 (1.10-3.03); p = 0.04]. Compared to subjects with Lp(a) levels in the lowest quintile, those within the highest quintile had a 3.2-times adjusted risk to suffer an acute ischaemic/nonembolic stroke (1.60-6.62, 95% CI; p < 0.001). Furthermore, analysis of interaction between lipid variables revealed that in the presence of elevated Lp(a) levels the inverse relationship between HDL-cholesterol levels and ischaemic stroke was negated [OR, 1.01 (1.00-1.03); p = 0.015]. Our study suggests that determination of Lp(a) levels and Apo(a) isoform size may be important in identifying elderly individuals at risk of ischaemic stroke independently of other risk factors and concurrent metabolic derangements.     

Association of serum uric acid with cardiovascular disease in rheumatoid arthritis

OBJECTIVES: Elevated serum uric acid (SUA) levels have been associated with cardiovascular disease (CVD) in the general population. Rheumatoid arthritis (RA) is not thought to associate with high SUA but is characterized by increased CVD morbidity and mortality. We aimed to explore a potential association of SUA with CVD in RA patients and to evaluate whether such an association is present when the traditional CVD risk factors are taken into account. METHODS:. 400 consecutive RA patients were recruited in this cross-sectional study and had all traditional CVD risk factors and SUA assessed. The association of SUA levels with other variables was assessed using bivariate correlations. Subsequent binary logistic models with appropriate adjustments were used to test the independence of the association between SUA and CVD. RESULTS: SUA levels were significantly higher in RA patients with CVD (RA + CVD) compared with RA patients without CVD (RA - CVD) (5.68 +/- 1.81 mg dl(-1) vs 5.06 +/- 1.41 mg dl(-1), P = 0.001). After adjusting for CVD risk factors, physical function (health assessment questionnaire, HAQ) and use of diuretics and/or statins the association between SUA and CVD in RA patients remained significant [Odds ratio (OR) = 1.36, 95% confidence interval (CI) 1.04-1.79, P = 0.025]. Compared with subjects with SUA levels in the lowest quintile (<3.86 mg dl(-1)), those within the highest quintile (>/=6.38 mg dl(-1)) had a 6-fold increase in the odds of having CVD (adjusted OR 6.46, 95% CI 1.66-25.05, P = 0.007). CONCLUSIONS: This cross-sectional study suggests that SUA may be independently associated with CVD in RA patients. This needs to be confirmed in prospective studies.     

Serum uric acid is independently associated with hypertension in patients with rheumatoid arthritis

Hypertension (HT) is highly prevalent in rheumatoid arthritis (RA). Serum uric acid (SUA) has been associated with HT in the general population. The mutual exclusion of gout and RA, and the systemic inflammatory component of RA may alter this association in this patient population. We explored a potential association between SUA levels and HT in RA and evaluated whether this association is independent of HT risk factors, RA characteristics and relevant drugs. A total of 400 consecutive RA patients were assessed. SUA and complete biochemical profile were measured. Demographic, HT-related factors, RA characteristics and drugs were assessed as potential covariates. Results were analysed using binary logistic models to test the independence of the association between SUA and HT. SUA levels were higher in hypertensive compared to normotensive RA patients (5.44+/-1.6 mg dl(-1) (323.57+/-95.17 micromol l(-1)) vs 4.56+/-1.1 mg dl(-1) (271.23+/-65.43 micromol l(-1)), P<0.001). When adjusted for HT risk factors, renal function, RA characteristics, non-steroidal anti-inflammatory drugs, oral prednisolone, cyclosporine, leflunomide and low-dose aspirin, the odds of being a hypertensive RA patient per 1 mg dl(-1)(59.48 micromol l(-1)) SUA increase were significantly increased: OR=1.59 (95% CI: 1.21-2.1, P=0.001). This was also significant for the subgroup of patients who were not on diuretics (OR=1.5, 95% CI: 1.1-2.05; P=0.011). This cross-sectional study suggests that SUA levels are independently associated with HT in RA patients. Prospective longitudinal studies are needed to confirm and further explore the causes and implications of this association.     

Risk factors for first-ever acute ischemic non-embolic stroke in elderly individuals

BACKGROUND: Stroke is a leading cause of mortality and subsequent serious long-term physical and mental disability among survivors. In the elderly, ischemic stroke accounts for more than 80% of all strokes. OBJECTIVES: To identify major risk factors for a first-ever acute ischemic/non-embolic stroke in individuals older than 70 years. METHODS: A population-based case-control study of patients admitted to the University Hospital of Ioannina, Epirus, Greece, due to first-ever ischemic/non-embolic stroke from March 1997 to January 2002. All patients were subjected to brain CT and had their serum lipids and biochemical metabolic parameters determined within 24 h from the onset of symptoms. RESULTS: A total of 163 (aged>70 years) consecutive stroke patients and 166 apparently healthy volunteers were studied. An atherogenic lipid profile and metabolic disturbances were more prevalent in the patient group than in stroke-free controls. Multivariate logistic regression analysis identified diabetes mellitus (odds ratio (OR), 1.92; 95% CI, 1.02-3.63), triglycerides (TG) (OR, 1.16; 95% CI, 1.09-1.22), HDL-cholesterol (OR, 0.57; 95% CI, 0.43-0.76), apo A-I (OR, 0.80; 95% CI, 0.70-0.92), lipoprotein(a) [LP(a)] (OR, 1.51; 95% CI, 1.25-1.79), uric acid (OR, 1.30; 95% CI, 1.06-1.59) albumin (OR, 0.38; 95% CI, 0.20-0.70) fibrinogen (OR, 1.10; 95% CI, 1.05-1.13) and the metabolic syndrome (OR 2.48, 95% CI, 1.16-5.29) as significantly associated with ischemic/non-embolic stroke. CONCLUSION: Ischemic non-embolic stroke in the elderly is associated with dyslipidemia and several predictor metabolic factors, which could be substantially modified by lifestyle changes and therapeutic intervention.     

Serum uric acid and long-term mortality from stroke, coronary heart disease and all causes.

BACKGROUND: Increased serum uric acid (SUA) levels are linked to obesity, dyslipidemia, diabetes and hypertension. Whether SUA carries a risk for coronary heart disease (CHD) and stroke remains uncertain. DESIGN: A prospective cohort study. METHODS: Of an original cohort of middle-aged workers who were examined in 1963 and followed-up for 23 years, 9125 men, free of CHD at entry, are included in this study. Subjects were divided into quintiles according to baseline SUA levels. Hazard ratios (HR) for all-cause, CHD, and stroke mortality were estimated in SUA quintiles, with the third serving as a referent. RESULTS: During follow-up, 2893 deaths were recorded, including 830 ascribed to CHD and 292 to stroke. The HR for all death [1.22, 95% confidence interval (CI) 1.09-1.37] and CHD (1.29, 95% CI 1.05-1.58) were increased in the upper SUA quintile. Fatal stroke showed a U-shaped relationship as both the upper (HR 1.48, 95% CI 1.02-2.17) and bottom (HR 1.43, 95% CI 0.99-2.08) quintiles were associated with a higher risk. Adjustment for confounders reduced the HR of the upper quintile for all outcomes, but did not attenuate the association of the bottom quintile with stroke (HR 1.52, 95% CI 1.04-2.23). When analysed separately by stroke type, the latter association seemed to be stronger for hemorrhagic (HR 3.27, 95% CI 1.14-9.33) than for ischemic stroke (HR 1.34, 95% CI 0.87-2.05). CONCLUSION: In addition to findings supporting increased mortality among hyperuricemic subjects, we identified an association between low SUA levels and fatal stroke, which deserves further investigation.     

Elevated uric acid increases the risk for acute kidney injury

BackgroundUric acid has been proposed to play a role in acute kidney injury. We therefore investigated the potential influence of preoperative serum uric acid (SUA) on acute kidney injury in patients undergoing cardiovascular (CV) surgery. The primary aims were to investigate the incidence of acute kidney injury, peak serum creatinine (SCr) concentrations, hospital length of stay, and days on mechanical ventilation.MethodsRetrospective study included patients who underwent CV surgery and had preoperative SUA available. Acute kidney injury was defined as an absolute increase in SCr ≥0.3 mg/dL from baseline within 48 hours after surgery. Univariate and multivariate logistic regression analysis was performed to determine the odds ratio for acute kidney injury.ResultsThere were 190 patients included for analysis. SUA were divided into deciles. The incidences of acute kidney injury were higher with higher deciles of SUA. When the incidences of acute kidney injury were plotted against all available values of SUA at increments of 0.5 mg/dL, a J-shaped curve emerged demonstrating higher incidences of acute kidney injury associated with both hypo- and hyperuricemia. In the univariate analysis, SUA ≥5.5 mg/dL was associated with a 4-fold (odds ratio [OR] 4.4; 95% confidence interval [CI], 2.4-8.2), SUA ≥6 mg/dL with a 6-fold (OR 5.9; 95% CI, 3.2-11.3), SUA ≥6.5 mg/dL with an 8-fold (OR 7.9; 95% CI, 3.9-15.8), and SUA ≥7 mg/dL with a 40-fold (OR 39.1; 95% CI, 11.6-131.8) increased risk for acute kidney injury. In the multivariate analysis, SUA ≥7 mg/dL also was associated with a 35-fold (OR 35.4; 95% CI, 9.7-128.7) increased risk for acute kidney injury. The 48-hour postoperative and hospital-stay mean peak SCr levels also were higher in the SUA ≥5.5 mg/dL group compared with the SUA <5 mg/dL group. SUA ≥7 mg/dL was associated with increased length of hospital stay (SUA <7 mg/dL, 18.5 ± 1.8 days vs SUA ≥7 mg/dL, 32.0 ± 6.8 days, P = 0.058) and a longer duration of mechanical ventilation support (SUA <7 mg/dL, 2.4 ± 0.4 days vs SUA ≥7 mg/dL, 20.4 ± 4.5 days, P = 0.001).ConclusionPreoperative SUA was associated with increased incidence and risk for acute kidney injury, higher postoperative SCr values, and longer hospital length of stay and duration of mechanical ventilation support in patients undergoing cardiac surgery. A J-shaped relationship appears to exist between SUA and acute kidney injury.     

Serum uric acid as an independent predictor of early death after acute stroke.

BACKGROUND: The prognostic significance of uric acid (UA) levels in acute stroke is unclear, so the objective of this study was to determine the association between levels of serum UA (SUA) and mortality in acute stroke. METHODS AND RESULTS: Consecutive patients (n=435) presenting with ischemic stroke and intracerebral hemorrhage were included in the study. The length of stay in hospital and the occurrence of death were recorded. On univariate analysis, the occurrence of death was associated with older age, smoking, presence of congestive heart failure or atrial fibrillation, absence of hyperlipidemia, and intracerebral hemorrhage as the index event. Furthermore, glucose, urea, creatinine and SUA at admission were significantly higher in patients who died, whereas total and high-density-lipoprotein cholesterol were significantly lower. On multiple logistic regression analysis, the independent relationship between higher SUA levels and death was confirmed (odds ratio (OR), 1.37; 95%confidence interval (CI), 1.13-1.67; p=0.001). The only other variables independently associated with the occurrence of death were urea concentration and presence of atrial fibrillation. If urate was >7.8 mg/dl (0.47 mmol/L), then there would be a high probability of early death (87%). CONCLUSIONS: Elevated levels of SUA are independently associated with an increased risk of early death in acute stroke.     

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.     

Predicting ischaemic stroke subtype from presenting systolic blood pressure: the BASIC Project

Objective. We hypothesized that low presenting systolic blood pressure (SBP) predicted cardioembolic stroke aetiology. Design. Active and passive surveillance were used to identify all ischaemic strokes as part of the Brain Attack Surveillance in Corpus Christi (BASIC) population‐based study. Multinomial logistic regression was used to examine the association between stroke subtype and first documented SBP in the medical record. Setting. Nueces County, TX, USA (313 645 residents in 2000). The community is urban with the majority of the population residing in the city of Corpus Christi. The area is served by seven adult acute care hospitals. Patients. Three hundred and eight cases with completed ischaemic stroke and determined subtype aetiology between January 2000 and December 2002. Results. Lower presenting SBP was associated with stroke subtype (P = 0.001). This association remained significant in the final model adjusted for age and history of coronary artery disease. The odds of cardioembolic versus small vessel occlusion increased by 20% (OR = 1.20, 95% CI: 1.07–1.35) for every 10 mmHg decrease in presenting SBP. Other covariates including race/ethnicity, gender, history of hypertension, and diabetes were neither significant predictors of stroke subtype, nor did they confound the association of SBP and stroke subtype. A 5 year increase in age increased the odds of cardioembolic subtype by 25% (OR = 1.25, 95% CI: 1.07–1.47). Conclusions. Lower initial SBP and older age at ischaemic stroke presentation were associated with cardioembolic stroke. Suspicion of cardioembolic stroke should be increased in those presenting with low SBP.     

Heart failure on admission and the risk of stroke following acute myocardial infarction: the VALIANT registry.

AIMS: We sought to assess the relative contribution of heart failure (HF) on admission for an acute myocardial infarction (MI) to the subsequent in-hospital stroke risk. METHODS AND RESULTS: The VALsartan In Acute myocardial iNfarcTion (VALIANT) registry enrolled 5573 consecutive MI patients at 84 international sites from 1999 to 2001. We calculated odds ratios (ORs) for stroke and adjusted for baseline characteristics, Killip Class, and risk factors for stroke, such as diabetes and prior HF. In-hospital stroke occurred in 81 (1.5%) patients. HF was present on admission in 38% of patients who developed a stroke and in 24% who did not (P=0.001). Older age (OR 1.03 increase/year, 95% confidence interval (CI) 1.01-1.04), Killip Class III (OR 1.66, CI 0.86-3.19) or IV (OR 4.85, CI 1.69-13.93), history of hypertension (OR 1.73, CI 1.06-2.82), and history of stroke (OR 1.89, CI 1.06-3.37) were more common in patients who had in-hospital stroke. In-hospital mortality in patients with and without stroke was 27.2 and 6.5%, respectively (P<0.001). CONCLUSION: Patients with stroke after MI have a dismal prognosis. The presence of HF on admission for an acute MI increases in-hospital stroke risk. HF treatments may modify the risk of stroke.     

Atrial fibrillation and stroke: clinical presentation of cardioembolic versus atherothrombotic infarction

The aim of the study was to compare demographic characteristics, anamnestic findings, cerebrovascular risk factors, and clinical and neuroimaging data of cardioembolic stroke patients with and without atrial fibrillation and of atherothrombotic stroke patients with and without atrial fibrillation. Predictors of early diagnosis of cardioembolic vs. atherothrombotic stroke infarction in atrial fibrillation patients were also determined. Data of cardioembolic stroke patients with (n=266) and without (n=81) atrial fibrillation and of atherothrombotic stroke patients with (n=75) and without (n=377) were obtained from 2000 consecutive patients included in the prospective Sagrat Cor-Alianza Hospital of Barcelona Stroke Registry. Risk factors, clinical characteristics and neuroimaging features in these subgroups were compared. The independent predictive value of each variable on early diagnosis of stroke subtype was assessed with a logistic regression analysis. In-hospital mortality in patients with atrial fibrillation was significantly higher than in non-atrial fibrillation patients both in cardioembolic (32.6% vs. 14.8%, P<0. 005) and atherothrombotic stroke (29.3% vs. 18.8%, P<0.04). Valvular heart disease (odds ratio (OR) 4.6; 95% confidence interval (95% CI) 1.19-17.68) and sudden onset (OR 1.8; 95% CI 0.97-3.63) were predictors of cardioembolic stroke, and subacute onset (OR 8; 95% CI 1.29-49.42), COPD (OR 5.2; 95% CI 1.91-14.21), hypertension (OR 3. 63; 95% CI 1.92-6.85), hypercholesterolemia (OR 2.67; 95% CI 1.13-6. 28), transient ischaemic attack (OR 2.49; 95% CI 1.05-5.90), ischaemic heart disease (OR 2.30; 95% CI 1.15-4.60) and diabetes (OR 2.26; 95% CI 1.14-4.47) of atherothrombotic stroke. In conclusion, some clinical features at stroke onset may help clinicians to differentiate cerebral infarction subtypes in patients with atrial fibrillation. Atrial fibrillation is associated with a higher in-hospital mortality both in cardioembolic and atherothrombotic stroke patients.     

急性缺血性卒中患者急性肾损伤的危险因素

目的 探讨缺血性卒中患者并发急性肾损伤(acute kidney injury, AKI)的危险因素.方法 回顾性纳入缺血性卒中患者,收集一般临床资料、血管危险因素、药物使用情况、卒中病因学分型、卒中严重程度和基线生化指标等.根据是否发生AKI分为并发AKI组和对照组.采用多变量logistic回归分析缺血性卒中患者发生AKI的独立危险因素.结果 共纳入214例缺血性卒中患者,其中32例(14.95%)发生AKI,182例(85.05%)未发生AKI.AKI组心力衰竭(62.50%对41.21%;χ2=4.998,P=0.025)、应用甘露醇(87.50%对43.96%;χ2=20.643,P<0.001)和呋塞米(87.50%对43.96%;χ2=20.643,P<0.001)、应用对比剂(37.50%对19.23%;χ2=5.300,P=0.021)和对比剂用量>200 ml(28.13%对9.89%;χ2=6.637,P=0.010)患者构成比以及NIHSS评分[(18.0±4.5)分对(8.0±3.2)分;t=15.249,P<0.001]、舒张压[(89.98±9.12)mmHg对(80.56±8.19)mmHg,1 mmHg=0.133 kPa;t=5.898,P<0.001]、空腹血糖[(10.54±4.31)mmol/L对(6.32±1.32)mmol/L;t=5.898,P<0.001]、血尿素氮水平[(11.21±2.13)mmol/L对(7.98±2.34)mmol/L;t=7.293,P<0.001]、动脉血乳酸浓度[(3.98±0.12)mmol/L对(0.91±0.25)mmol/L;t=68.003,P<0.001]均显著高于非AKI组.多变量logistic回归分析示,在校正各种混杂因素后,NIHSS评分较高[优势比(odds ratio, OR) 1.910,95%可信区间(confidence interval, CI) 1.517~6.012;P=0.024]、舒张压较高(OR 1.816,95% CI 1.652~3.876;P=0.018)、动脉血乳酸浓度(OR 1.553,95% CI 1.256~1.763;P=0.019)、应用脱水剂(甘露醇:OR 3.765,95% CI 2.081~9.658,P=0.017;呋塞米:OR 5.329,95% CI 3.085~8.763,P=0.010)、应用对比剂(OR 2.097,95% CI 1.364~2.456;P=0.031)以及对比剂>200 ml(OR 3.294,95% CI 1.464~2.786;P=0.021)是缺血性卒中患者AKI的独立危险因素.结论 NIHSS评分、舒张压、动脉血乳酸浓度、应用甘露醇和呋塞米以及应用对比剂和对比剂剂量>200 ml与缺血性卒中患者AKI独立相关.     

Using structural equation model to illustrate the relationship between metabolic risk factors and cardiovascular complications in Taiwan.

BACKGROUND: The objective of this study was to perform a population-based screening programme to determine the prevalence of the metabolic syndrome (MetS) and the relationship between metabolic risk factors and prevalent cardiovascular complications in Taiwan. DESIGN: A screening programme recruited residents aged 40 years and older in Sanchih, Taipei County, Taiwan, and collected demographic data, blood and urine samples. Fasting plasma glucose level, serum total cholesterol, high-density lipoprotein cholesterol, and triglyceride were measured. Atherosclerotic complications, including myocardial infarction, stress-positive angina, ischaemic stroke, and proteinuria were confirmed. METHODS: A structural equation model (SEM) was constructed to identify the association between metabolic abnormality and atherosclerosis. RESULTS: A total of 1494 subjects, 776 male and 718 female, were recruited in this study. The crude prevalence of the MetS was 19.3% for men [95% confidence interval (CI) 16.3-22.2%] and 18.7% for women (95% CI 15.6-22.0%). The presence of the MetS posed a substantial risk to microvascular complications in both sexes [odds ratio (OR) 3.29, P<0.001] and to macrovascular complications in men (OR 1.95, P=0.04) and also a trend in women (OR 2.24, P=0.089). There was a positive association between metabolic abnormality and atherosclerosis (B=0.55, P<0.001). CONCLUSIONS: This study has found the prevalence of the MetS and the association with atherosclerotic complications in Taiwan. The SEM approach has demonstrated a positive correlation between metabolic abnormality and atherosclerosis and can be used to explore new risk factors for cardiovascular diseases.     

Pulse pressure is independently associated with carotid plaque ulceration

BACKGROUND: Plaque rupture is the principal cause of acute coronary ischaemia, and unstable carotid plaques are associated with a high risk of ischaemic stroke. Carotid plaque ulceration also predicts acute coronary events, suggesting that systemic factors may determine plaque instability. One potentially important factor is pulse pressure. There is indirect evidence that cyclical haemodynamic forces affect plaque stability, and pulse pressure is a strong predictor of coronary events. OBJECTIVE: To study the association between pulse pressure and plaque ulceration. DESIGN AND METHODS: We studied angiograms from 3007 patients with recently symptomatic carotid stenosis in the European Carotid Surgery Trial. Presence of ulceration was related to the different components of blood pressure [pulse pressure, systolic blood pressure (SBP), mean arterial pressure (MAP), and diastolic blood pressure (DBP)], and adjustment was made for age, sex, diabetes, smoking, and the degree of vessel stenosis. RESULTS: Pulse pressure was the strongest independent predictor of ulceration of the symptomatic carotid plaque [adjusted odds ratio (OR) for the upper compared with the lower quintile 2.07, 95% confidence interval (CI) 1.25 to 3.44; P = 0.004]. This relationship was weaker for SBP (OR 1.66, 95% CI 1.05 to 2.62; P = 0.02), and non-significant for MAP (OR 1.58, 95% CI 1.01 to 2.48, P = 0.13) and DBP (OR 1.67, 95% CI 0.73 to 1.87, P = 0.50). CONCLUSIONS: Pulse pressure is independently associated with carotid plaque ulceration, supporting the hypothesis that pulsatile haemodynamic forces are an important cause of plaque rupture.     

Serum homocysteine, folate and risk of stroke: Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study.

BACKGROUND: Homocysteine and folate have been suggested to have opposite effects on the risk of stroke, although the results are controversial. DESIGN AND METHODS: The purpose of this study was to assess the effects of serum total homocysteine (tHcy) and serum folate levels on the risk of stroke in a prospective cohort study. The subjects were 1015 men aged 46-64 years and free of prior stroke, examined in 1991-1993 in the Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study. RESULTS: At baseline the mean serum tHcy concentration was 10.9 micromol/l (SD 3.4). During an average follow-up time of 9.6 years, 49 men experienced a stroke, of which 34 were ischaemic. In Cox proportional hazards models, men in the highest tHcy third had a risk factor-adjusted hazard rate ratio (RR) of 2.77 [95% confidence interval (CI): 1.23-6.24] for any stroke and 2.61 (95% CI: 1.02-6.71) for ischaemic stroke, compared with men in the lowest third. The mean baseline serum folate concentration was 10.4 nmol/l (SD 4.1). Men in the highest third of serum folate (>11.2 nmol/l) had an adjusted RR for any stroke of 0.35 (95% CI: 0.14-0.87) and for ischaemic stroke of 0.40 (95% CI: 0.15-1.09), compared with men in the lowest third. CONCLUSION: Elevated serum tHcy is associated with increased risk of all strokes and ischaemic strokes in middle-aged eastern Finnish men free of prior stroke. On the other hand, high serum folate concentration may protect against stroke.     

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.     

Serum C-reactive protein levels and death and cardiovascular events in mild to moderate chronic kidney disease

Chronic kidney disease (CKD) is associated with an increased risk of cardiovascular (CV) disease. Elevated circulating levels of high sensitivity C-reactive protein (hsCRP) have been suggested to be associated with high risk of CV disease. It is uncertain whether the CV risk in CKD can be stratified by hsCRP levels in the Japanese population. Baseline data including serum hsCRP and creatinine levels were determined in the general population. Estimated glomerular filtration rate (eGFR) was calculated using a modified MDRD equation, and CKD was defined as eGFR below 60 mL/minute/1.73m(2). We analyzed 1,074 male subjects with mild to moderate CKD (mean age, 70.4 years). CV events (stroke and myocardial infarction) and all-cause death were surveyed prospectively. The CKD subjects were followed for 5.1 years, and 72 CV events and 115 all-cause deaths were found (composite endpoint). After adjustment for established CV risk factors, hazard ratios (HRs) for the endpoint were significantly increased according to the hsCRP quintile (P < 0.001), and HR for the highest (versus the lowest) quintile was 2.77 (95% CI; 1.61-4.77). These results suggest that serum hsCRP measurement is a useful tool for the risk stratification of CV events and death in CKD male subjects selected from the general population.     

A case control study between diabetic and non-diabetic subjects with ischemic stroke.

AIM: The clinical and prognostic profile of diabetic stroke patients is still an unclarified topic. The aim of the present study is to compare clinical features and risk factor profile in diabetics and in non-diabetics affected by acute ischemic stroke. METHODS: We have included 98 diabetics and 102 matched non-diabetic subjects affected by acute ischemic stroke and matched by age (+/-3 years) and gender. We determined the Scandinavian Stroke Scale (SSS) on admission and the Rankin disability scale on discharge and after a 6 months follow-up. Ischemic stroke has been classified according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification. We anamnestically evaluated the presence of hypertension, hypercholesterolemia, any records of transient ischemic attack, and stroke. Using conditional logistic regression analysis, we calculated adjusted odds ratio (OR) and 95% confidence interval (CI). RESULTS: Diabetes was associated with lacunar ischemic stroke subtype (OR 3.89, 95% CI 2.23-6.8), with a record of hypertension (OR 2.53, 95% CI 1.48-4.32), and with a better SSS score at admission (OR 0.58, 95% CI 0.36-0.96). The association of diabetes with lacunar stroke remained significant also after adjustment for hypertension (adjusted OR 3.37, 95% CI 1.9-5.99) or for large artery atherosclerotic and cardioembolic stroke subtypes (adjusted OR 2.69, 95% CI 1.08-6.69). CONCLUSIONS: Our study shows some significant differences in acute ischemic stroke among diabetics in comparison with non-diabetics (higher frequency of hypertension, higher prevalence of lacunar stroke subtype, lower neurological deficit at admission in diabetics).     

Serum homocysteine,thermolabile variant of methylene tetrahydrofolate reductase (MTHFR), and venous thromboembolism: Longitudinal Investigation of Thromboembolism Etiology (LITE)

We sought to examine prospectively the association of serum homocysteine and the methylene tetrahydrofolate reductase (MTHFR) C677T gene polymorphism with risk of venous thromboembolism (VTE). We studied these relationships in a nested case-control study of 303 VTE cases and 635 matched controls from a population-based cohort of 21,680 adults from six U.S. communities. The highest quintile of serum homocysteine carried a non-statistically significant adjusted odds ratio of 1.55 (95% CI, 0.93-2.58) compared to the lowest quintile in the overall cohort but a significant association among adults aged 45-64 years (OR = 2.05, 95% CI, 1.10-3.83) and an inverse association in those > or = 65 years of age. Carriers of the MTHFR C677T polymorphism were not at higher risk for VTE than those with normal genotype (OR = 0.74, 95% CI = 0.56-0.98). Our prospective data showed, at most, a weak relationship between homocysteine and VTE risk, with associations larger among younger participants. MTHFR C677T was not a risk factor for VTE.     

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.