Reversible regulation of SHP-1 tyrosine phosphatase activity by oxidation

BACKGROUND AND PURPOSE: Randomized clinical trials testing aspirin in relatively low-risk, middle-aged people have consistently shown small increases in stroke associated with aspirin use. We analyzed the relationship between the regular use of aspirin and incident ischemic and hemorrhagic stroke among people aged 65 years or older participating in the Cardiovascular Health Study. METHODS: We conducted a multivariate analysis of incident stroke rates in a prospectively assessed, observational cohort of 5011 elderly people followed for a mean of 4.2 years. RESULTS: Participants had a mean age of 72 years, and 58% were women. Twenty-three percent used aspirin frequently, and 17% used aspirin infrequently at study entry. Frequent aspirin use was associated with an increased rate of ischemic stroke compared with nonusers (relative risk= 1.6; 95% confidence interval [CI], 1.2 to 2.2; P=0.001). After adjustment for other stroke risk factors, women who used aspirin frequently or infrequently at study entry had a 1.8-fold (95% CI, 1.2 to 2.8) and 1.6-fold (95% CI, 0.9 to 3.0) increased risk of ischemic stroke, respectively (P<0.01, test for trend), compared with nonusers. In men, aspirin use was not statistically significantly associated with stroke risk. Findings were similar when aspirin use in the years before the incident stroke was used in the modeling. Aspirin use at entry was also associated with a 4-fold (95% CI, 1.6 to 10.0) increase in risk of hemorrhagic stroke for both infrequent and frequent users of aspirin (P=0.003). CONCLUSIONS: Aspirin use was associated with increased risks of ischemic stroke in women and hemorrhagic stroke overall in this elderly cohort, after adjustment for other stroke predictors. The possibility exists of confounding by reasons for aspirin use rather than cause and effect. Whether regular aspirin use increases stroke risk for elderly people without cardiovascular disease can only be determined by randomized clinical trials.     

Serum creatinine concentration and risk of cardiovascular disease: a possible marker for increased risk of stroke

BACKGROUND AND PURPOSE: Elevated serum creatinine has been associated with increased mortality in hypertensive persons, the elderly, and patients with myocardial infarction or stroke in whom cardiovascular disease is the major cause of death. We have examined the relationship between serum creatinine concentration and the risk of major ischemic heart disease and stroke events and all-cause mortality in a general population of middle-aged men. METHODS: We present a prospective study of middle-aged men (aged 40 to 59 years) drawn from 24 British towns who have been followed up for an average of 14.75 years. Data on serum creatinine were available for 7690 men in whom there were 287 major stroke events, 967 major ischemic heart disease events, and 1259 deaths from all causes during follow-up. RESULTS: The median serum creatinine concentration was 98 micromol/L (95% range, 76 to 129 micromol/L). Stroke risk was significantly increased at levels above 116 micromol/L (90th percentile) even after adjustment for a wide range of cardiovascular risk factors (relative risk [RR], 1.6; 95% CI, 1.1 to 2.1; > 116 micromol/L versus the rest). Risk of a major ischemic heart disease event was significantly increased at or above 130 micromol/L (97.5 percentile), but this was attenuated after adjustment (RR, 1.2; 95% CI, 0.8 to 1.7; > or = 130 micromol/L versus the rest). There was a weak but significant positive association between diastolic blood pressure and creatinine concentration. However, elevated creatinine concentration (> or = 116 micromol/L) was associated with a significant increase in stroke in both normotensive and hypertensive men. All-cause mortality and overall cardiovascular mortality were significantly increased only above the 97.5 percentile, and no significant association was seen with cancer or other noncardiovascular mortality. CONCLUSIONS: A high serum creatinine concentration within the normal range is a marker for increased risk of cerebrovascular disease in both normotensive and hypertensive subjects. These findings support the evidence indicating that subtle impairment of renal function is a factor for increased risk of stroke and suggest mechanisms in the pathogenesis of stroke that warrant further investigation.     

Fixed minidose warfarin and aspirin alone and in combination vs adjusted-dose warfarin for stroke prevention in atrial fibrillation: Second Copenhagen Atrial Fibrillation, Aspirin, and Anticoagulation Study

BACKGROUND: Despite the efficacy of warfarin sodium therapy for stroke prevention in atrial fibrillation, many physicians hesitate to prescribe it to elderly patients because of the risk for bleeding complications and because of inconvenience for the patients. METHODS: The Second Copenhagen Atrial Fibrillation, Aspirin, and Anticoagulation Study was a randomized, controlled trial examining the following therapies: warfarin sodium, 1.25 mg/d; warfarin sodium, 1.25 mg/d, plus aspirin, 300 mg/d; and aspirin, 300 mg/d. These were compared with adjusted-dose warfarin therapy (international normalized ratio of prothrombin time [INR], 2.0-3.0). Stroke or a systemic thromboembolic event was the primary outcome event. Transient ischemic attack, acute myocardial infarction, and death were secondary events. Data were handled as survival data, and risk factors were identified using the Cox proportional hazards model. The trial was scheduled for 6 years from May 1, 1993, but due to scientific evidence of inefficiency of low-intensity warfarin plus aspirin therapy from another study, our trial was prematurely terminated on October 2, 1996. RESULTS: We included 677 patients (median age, 74 years). The cumulative primary event rate after 1 year was 5.8% in patients receiving minidose warfarin; 7.2%, warfarin plus aspirin; 3.6%, aspirin; and 2.8%, adjusted-dose warfarin (P = .67). After 3 years, no difference among the groups was seen. Major bleeding events were rare. CONCLUSIONS: Although the difference was insignificant, adjusted-dose warfarin seemed superior to minidose warfarin and to warfarin plus aspirin after 1 year of treatment. The results do not justify a change in the current recommendation of adjusted-dose warfarin (INR, 2.0-3.0) for stroke prevention in atrial fibrillation.     

Stroke and use of low-dose oral contraceptives in young women: a pooled analysis of two US studies

BACKGROUND AND PURPOSE: The available data on low-dose oral contraceptive pill (OCP) use and stroke risk in US women are limited by small numbers. We sought more precise estimates by conducting a pooled analysis of data from 2 US population-based case-control studies. METHODS: We analyzed interview data from 175 ischemic stroke cases, 198 hemorrhagic stroke cases, and 1191 control subjects 18 to 44 years of age. RESULTS: For ischemic stroke, the pooled odds ratio (pOR) adjusted for stroke risk factors for current use of low-dose OCPs compared with women who had never used OCP (never users) was 0.66 (95% confidence interval [CI], 0.29 to 1.47) and compared with women not currently using OCPs (nonusers) the pOR was 1.09 (95% CI, 0.54 to 2.21). For hemorrhagic stroke, the pOR for current use of low-dose OCPs compared with never users was 0.95 (95% CI, 0.46 to 1.93) and compared with nonusers the pOR was 1.11 (95% CI, 0.61 to 2.01). The pORs for current low-dose OCP use and either stroke type were not elevated among women who were >/=35 years, cigarette smokers, obese, or not receiving medical therapy for hypertension. pORs for current low-dose OCP use were 2.08 (95% CI, 1. 19 to 3.65) for ischemic stroke and 2.15 (95% CI, 0.85 to 5.45) for hemorrhagic stroke among women reporting a history of migraine but were not elevated among women without such a history. Past OCP use (irrespective of formulation) was inversely related to ischemic stroke but unrelated to hemorrhagic stroke. CONCLUSIONS: Women who use low-dose OCPs are, in the aggregate, not at increased risk of stroke. Studies are needed to clarify the risk of stroke among users who may be susceptible on the basis of age, smoking, obesity, hypertension, or migraine history.     

Incidence and characteristics of fall-related emergency department visits

BACKGROUND: Patients with acute ischemic syndromes (AIS) suffer high rates of recurrent ischemic events despite aspirin treatment. Long-term therapy with oral anticoagulants in addition to aspirin may reduce this risk. We studied the effects of long-term warfarin at 2 intensities in patients with AIS without ST elevation in 2 consecutive randomized controlled studies. METHODS AND RESULTS: In phase 1, after the cessation of 3 days of intravenous antithrombotic therapy, 309 patients were randomized to receive fixed low-dose (3 mg/d) warfarin for 6 months that produced a mean international normalized ratio (INR) of 1.5+/-0.6 or to standard therapy. Eighty-seven percent of patients received aspirin in both groups. The rates of cardiovascular (CV) death, new myocardial infarction (MI), and refractory angina at 6 months were 6.5% in the warfarin group and 3.9% in the standard therapy group (relative risk [RR], 1. 66; 95% CI, 0.62 to 4.44; P=0.31). The rates of death, new MI, and stroke were 6.5% in the warfarin group and 2.6% in the standard therapy group (RR, 2.48; 95% CI, 0.80 to 7.75; P=0.10). The overall rate of rehospitalization for unstable angina was 21% and did not differ significantly between the groups. Four patients in the warfarin group (2.6%) and none in the control group experienced a major bleed (RR, 2.48; 95% CI, 0.80 to 7.75), and there was a significant excess of minor bleeds in the warfarin group (14.2% versus 2.6%; RR, 5.46; 95% CI, 1.93 to 15.5; P=0.001). In phase 2, the protocol was modified, and 197 patients were randomized <48 hours from the onset of symptoms to receive warfarin at an adjusted dose that produced a mean INR of 2.3+/-0.6 or standard therapy for 3 months. Eighty-five percent received aspirin in both groups. The rates of CV death, new MI, and refractory angina at 3 months were 5. 1% in the warfarin group and 12.1% in the standard group (RR, 0.42; 95% CI, 0.15 to 1.15; P=0.08). The rates of all death, new MI, and stroke were 5.1% in the warfarin group and 13.1% in the standard therapy group (RR, 0.39; 95% CI, 0.14 to 1.05; P=0.05). Significantly fewer patients were rehospitalized for unstable angina in the warfarin group than in the control group (7.1% and 17.2%, respectively; RR, 0.42; 95% CI, 0.18 to 0.96; P=0.03). Two patients in the warfarin group and 1 in the control group experienced a major bleed, and there was a significant excess of minor bleeds in the warfarin group (28.6% versus 12.1%; RR, 2.36; 95% CI, 1.37 to 4.36; P=0.004). CONCLUSIONS: Long-term treatment with moderate-intensity warfarin (INR, 2.0 to 2.5) plus aspirin but not low-intensity warfarin (INR, 1.5) plus aspirin appears to reduce the rate of recurrent ischemic events in patients with AIS without ST elevation.     

Effects of sodium restriction on blood pressure, renin, aldosterone, catecholamines, cholesterols, and triglyceride: a meta-analysis

CONTEXT: One of the controversies in preventive medicine is whether a general reduction in sodium intake can decrease the blood pressure of a population and thereby reduce the number of strokes and myocardial infarctions. In recent years the debate has been extended by studies indicating that reduced sodium intake has adverse effects. OBJECTIVE: To estimate the effects of reduced sodium intake on systolic and diastolic blood pressure (SBP and DBP), body weight, and plasma or serum levels of renin, aldosterone, catecholamines, cholesterols, and triglyceride, and to evaluate the stability of the blood pressure effect in relation to additional trials. DATA SOURCES: MEDLINE search from 1966 through December 1997 and reference lists of relevant articles. STUDY SELECTION: Studies randomizing persons to high-sodium and low-sodium diets were included if they evaluated at least one of the effect parameters. DATA EXTRACTION: Two authors independently recorded data. DATA SYNTHESIS: In 58 trials of hypertensive persons, the effect of reduced sodium intake as measured by urinary sodium excretion (mean, 118 mmol/24 h) on SBP was 3.9 mm Hg (95% confidence interval [CI], 3.0-4.8 mm Hg) (P<.001) and on DBP was 1.9 mm Hg (95% CI, 1.3-2.5 mm Hg) (P<.001). In 56 trials of normotensive persons, the effect of reduced sodium intake (mean, 160 mmol/24 h) on SBP was 1.2 mm Hg (95% CI, 0.6-1.8 mm Hg) (P<.001) and on DBP was 0.26 mm Hg (95% CI, -0.3-0.9 mm Hg) (P=.12). The cumulative analysis showed that this effect size has been stable since 1985. In plasma, the renin level increased 3.6-fold (P<.001), and the aldosterone level increased 3.2-fold (P<.001); the increases were proportional to the degree of sodium reduction for both renin (r=0.66; P<.001) and aldosterone (r=0.64; P<.001). Body weight decreased significantly, and noradrenaline, cholesterol, and low-density lipoprotein cholesterol levels increased. There was no effect on adrenaline, triglyceride, and high-density lipoprotein cholesterol. CONCLUSION: These results do not support a general recommendation to reduce sodium intake. Reduced sodium intake may be used as a supplementary treatment in hypertension. Further long-term studies of the effects of high reduction of sodium intake on blood pressure and metabolic variables may clarify the disagreements as to the role of reduced sodium intake, but ideally trials with hard end points such as morbidity and survival should end the controversy.     

Clinical characteristics determining the mode of presentation in patients with acute coronary syndromes

OBJECTIVES: The purpose of this study was to examine clinical characteristics of patients with acute coronary syndromes to identify factors that influence the mode of presentation. BACKGROUND: In acute coronary syndromes, presentation with myocardial infarction or unstable angina has major prognostic implications, yet clinical factors affecting the mode of presentation are not well defined. METHODS: A prospective cohort study was made of 1,111 patients with acute coronary syndromes. Baseline demographic, clinical and biochemical data were compared in groups with myocardial infarction (n = 633) and unstable angina (n = 478). RESULTS: The risk of myocardial infarction relative to unstable angina was increased by age >70 years (odds ratio [OR] 2.21; 95% confidence interval [CI] 1.33 to 3.66), male gender (OR 1.56; CI 1.13 to 2.16) and cigarette smoking (OR 1.49; CI 1.09 to 2.03). A rise in admission creatinine from the 10th to the 90th centile of the distribution also increased the odds of myocardial infarction (OR 1.30; CI 1.05 to 1.94). Conversely, the risk of myocardial infarction relative to unstable angina was reduced by previous treatment with aspirin (OR 0.37; CI 0.27 to 0.52), hypertension (OR 0.64; CI 0.47 to 0.86) and previous acute coronary syndromes (OR 0.36; CI 0.26 to 0.51) and revascularization procedures (OR 0.36; CI 0.21 to 0.62). CONCLUSIONS: The clinical presentation of acute coronary syndromes may be influenced by various factors that have the potential to influence the coagulability of the blood, the collateralization of the coronary circulation and myocardial mass. Myocardial infarction is favored by cigarette smoking, advanced age and renal impairment, while unstable angina is favored by treatment with aspirin, hypertension, previous revascularization and previous coronary syndromes.     

Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study

CONTEXT: Although cholesterol-reducing treatment has been shown to reduce fatal and nonfatal coronary disease in patients with coronary heart disease (CHD), it is unknown whether benefit from the reduction of low-density lipoprotein cholesterol (LDL-C) in patients without CHD extends to individuals with average serum cholesterol levels, women, and older persons. OBJECTIVE: To compare lovastatin with placebo for prevention of the first acute major coronary event in men and women without clinically evident atherosclerotic cardiovascular disease with average total cholesterol (TC) and LDL-C levels and below-average high-density lipoprotein cholesterol (HDL-C) levels. DESIGN: A randomized, double-blind, placebo-controlled trial. SETTING: Outpatient clinics in Texas. PARTICIPANTS: A total of 5608 men and 997 women with average TC and LDL-C and below-average HDL-C (as characterized by lipid percentiles for an age- and sex-matched cohort without cardiovascular disease from the National Health and Nutrition Examination Survey [NHANES] III). Mean (SD) TC level was 5.71 (0.54) mmol/L (221 [21] mg/dL) (51 st percentile), mean (SD) LDL-C level was 3.89 (0.43) mmol/L (150 [17] mg/dL) (60th percentile), mean (SD) HDL-C level was 0.94 (0.14) mmol/L (36 [5] mg/dL) for men and 1.03 (0.14) mmol/L (40 [5] mg/dL) for women (25th and 16th percentiles, respectively), and median (SD) triglyceride levels were 1.78 (0.86) mmol/L (158 [76] mg/dL) (63rd percentile). INTERVENTION: Lovastatin (20-40 mg daily) or placebo in addition to a low-saturated fat, low-cholesterol diet. MAIN OUTCOME MEASURES: First acute major coronary event defined as fatal or nonfatal myocardial infarction, unstable angina, or sudden cardiac death. RESULTS: After an average follow-up of 5.2 years, lovastatin reduced the incidence of first acute major coronary events (1 83 vs 116 first events; relative risk [RR], 0.63; 95% confidence interval [CI], 0.50-0.79; P<.001), myocardial infarction (95 vs 57 myocardial infarctions; RR, 0.60; 95% CI, 0.43-0.83; P=.002), unstable angina (87 vs 60 first unstable angina events; RR, 0.68; 95% CI, 0.49-0.95; P=.02), coronary revascularization procedures (157 vs 106 procedures; RR, 0.67; 95% CI, 0.52-0.85; P=.001), coronary events (215 vs 163 coronary events; RR, 0.75; 95% CI, 0.61-0.92; P =.006), and cardiovascular events (255 vs 194 cardiovascular events; RR, 0.75; 95% CI, 0.62-0.91; P = .003). Lovastatin (20-40 mg daily) reduced LDL-C by 25% to 2.96 mmol/L (115 mg/dL) and increased HDL-C by 6% to 1.02 mmol/L (39 mg/dL). There were no clinically relevant differences in safety parameters between treatment groups. CONCLUSIONS: Lovastatin reduces the risk for the first acute major coronary event in men and women with average TC and LDL-C levels and below-average HDL-C levels. These findings support the inclusion of HDL-C in risk-factor assessment, confirm the benefit of LDL-C reduction to a target goal, and suggest the need for reassessment of the National Cholesterol Education Program guidelines regarding pharmacological intervention.     

Secondary prevention of arteriosclerosis

Secondary prevention of arteriosclerosis tries to inhibit progression of the atherosclerotic process. Therapeutic measures focus on modification of cardiovascular risk factors and antithrombotic treatment. Hypercholesterolemia is the main risk factor for coronary artery disease. The risk of a coronary event is correlated to the plasma cholesterol level. Lowering plasma cholesterol results in reduction of vascular morbidity and mortality. Cigarette smoking is the predominant risk factor for peripheral arterial occlusive disease (PAOD). Smoking cessation reduces progression of PAOD and lowers cardiovascular morbidity and mortality. The preventive effect of antihypertensive therapy in hypertensive patients is most pronounced for cerebrovascular events. Antihypertensive measures improve prognosis after stroke and myocardial infarction. The increased cardiovascular risk in diabetics is in part explained by hyperglycemia and hyperinsulinemia, but also depends on coexisting dyslipidemia and hypertension. Intensive treatment of elevated blood glucose levels, dyslipidemia and hypertension are important preventive measures. Aspirin is highly effective in secondary prevention of vascular events. For the coronary arteries, low-dose aspirin is well established. Whether low-dose aspirin is equally effective for reducing progression of arteriosclerosis in the cerebrovascular and in the peripheral vessels is questionable. Ticlopidine serves as an alternative to aspirin; however, neutropenia may occur, which requires supervision of the patient.     

Dementia after first stroke

BACKGROUND AND PURPOSE: Cognitive deficits may significantly worsen the quality of life after stroke. Our aim was to determine the frequency of dementia in a consecutive series of previously nondemented patients between the ages of 40 and 79 years at 3 months after a first ischemic stroke. METHODS: All patients admitted to our department during an 18-month period who met the above criteria were visited and tested and underwent a CT scan 3 months after their stroke. Dementia was diagnosed according to criteria of the National Institute of Neurological Disorders and Stroke and AIREN, but cases with aphasia were not excluded. RESULTS: Of 304 patients admitted for stroke, 146 were eligible for study. Eleven refused to participate, 25 were dead at 3 months, and 110 were tested. Fifteen patients were demented (13.6%; 95% confidence interval [CI], 7.8% to 21.5%), and six had severe isolated aphasia, neglect, or memory deficit (5.4%). Excluding patients with aphasia, 5.0% of cases showed dementia (95% CI, 1.6% to 11.3%). The frequency of dementia was 24.6% (95% CI, 14.5% to 37.3%), considering only patients with supratentorial lesions and with residual deficits of elementary functions (paresis, sensory deficits) at the time of examination. Demented patients had significantly more diabetes (P<.029), atrial fibrillation (P=.032), aphasia at entry (P<.001), large middle cerebral artery infarctions (P=.001), and a more severe neurological deficit at entry (P=.003) and at 3 months (P=.001). At CT scan, demented patients had a larger mean volume of the recent lesion (P<.001) and more lesions in the frontal lobe (P=.041). An exploratory multivariate analysis selected age between 60 and 69 years (odds ratio [OR], 45.8; 95% CI, 2.9 to 726.0), diabetes (OR 59.4; 95% CI, 4.3 to 821.0), aphasia (OR, 14.8; 95% CI, 2.0 to 111.0), a large middle cerebral artery infarction (OR, 30.0; 95% CI, 2.7 to 334.0), and lesions of the frontal lobe (OR, 9.8; 95% CI, 1.3 to 72.8) as significant independent correlates of poststroke dementia. CONCLUSIONS: Dementia is relatively frequent after a clinical first stroke in persons younger than 80 years, and aphasia is very often associated with poststroke dementia. If aphasic patients are not considered, it may be necessary to screen a very large number of subjects to collect an adequate sample of demented cases.     

Superiority of nitrate-enhanced 201Tl over conventional redistribution 201Tl imaging for prognostic evaluation after myocardial infarction and thrombolysis

BACKGROUND: 201Tl imaging has been widely used for postinfarction risk stratification. However, thrombolytic therapy and aspirin have significantly changed outcome, and there are few nuclear imaging studies that assess prognosis in such patients. Furthermore, newer techniques of 201Tl imaging, such as reinjection and nitrate-enhanced rest 201Tl imaging, have been shown to improve the detection of viable but jeopardized myocardium. METHODS AND RESULTS: We studied 100 consecutive patients, who remained event free 6 weeks after myocardial infarction and thrombolysis. Patients underwent conventional exercise and 4-hour redistribution imaging, followed on a separate day by nitrate-enhanced rest 201Tl study. Planar images were reported semiquantitatively by two experienced observers blinded to clinical data. Redistribution and rest injection images were classified as demonstrating reversible ischemia if they showed improvement in uptake by at least two grades in at least two segments in comparison with the initial exercise scintigram. Patients were followed up for 8 to 32 months (mean, 21 months); during this period, 37 patients had first cardiac events. Reversible ischemia was present in 29 patients on redistribution, of whom 14 (48%) had events; of 71 without reversible defects, 23 (32%) had events (hazard ratio, 1.5; 95% CI, 0.8 to 3.0; P=NS). Nitrate-enhanced rest 201Tl imaging detected reversible defects in 68 patients, of whom 33 (49%) had events, whereas of 32 without reversible defects, only 4 (13%) had subsequent cardiac events (hazard ratio, 8.1; 95% CI, 2.7 to 23.8; P<.001). CONCLUSIONS: Thus, after myocardial infarction and thrombolysis, even "stable" patients have a high (68%) incidence of viable but jeopardized myocardium, causing a high event rate. Those identified to be at high risk by perfusion imaging may benefit from early intervention.     

Stroke was predicted by dimensions of quality of life in treated hypertensive men

BACKGROUND AND PURPOSE: Psychosocial factors have been suggested as risk factors for atherosclerotic disease. The purpose of the present study was to examine whether quality of life predicted strokes and acute coronary events in a prospective study. METHODS: The study included 412 treated hypertensive men, aged 50 to 72 years, with >/=1 of the following: serum cholesterol >/=6.5 mmol/L, smoking, or diabetes mellitus. The Minor Symptoms Evaluation Profile (MSEP) was used to estimate quality of life at entry. Incidences of stroke and acute coronary events were recorded during follow-up. The median follow-up time was 6.6 years. RESULTS: Sixty-four patients had an acute coronary event, and 37 had a stroke during the follow-up period. The Cox regression analyses revealed that the 3 dimensions of MSEP at entry were significant predictors of stroke. The relationship between low contentment at entry and the incidence of stroke during follow-up remained significant (relative risk=1.04; 95% CI, 1.01 to 1.06; P=0.003) even after adjustment for other potential cardiovascular risk factors. Vitality also remained an independent predictor for stroke after adjustment for these potential cardiovascular risk factors (relative risk=1.04; 95% CI, 1. 02 to 1.06; P<0.0001). There was no relationship between MSEP score at entry and myocardial infarction during follow-up. CONCLUSIONS: An independent and significant association between reduced well-being at entry and future stroke was observed in hypertensive men at high cardiovascular risk. The causal relationship is not known, however.     

Should individuals without evidence of coronary disease and with risk factors receive continuous treatment with aspirin? Arguments against

There is a widespread opinion, above the non-scientific press, of the fact that it is demonstrated the aspirin usefulness in the primary prevention of the ischemic heart disease. This feeling is based on the results of the Physicians' Health Study. This wrong position is stablished on the significant reduction of the risk of myocardial infarction, since even though this study demonstrated a very significant, but there were also a non significant excess of hemorrhagic strokes and of sudden death among the physicians on aspirin treatment. For this reason the Physicians' Health Study demonstrated no effect on the cardiovascular mortality neither on the total mortality, that was the main objective of this study. On the other hand, all the primary prevention trials employing aspirin, have demonstrated also a significant excess of gastrointestinal bleeding complications. While is unquestionable the beneficial effect of the aspirin in the secondary prevention of patients with previous ischemic heart disease, the complications that aspirin may produce with its employment in healthy subjects, counterbalance the possible beneficial effect of the reduction of the incidence of myocardial infarction in a low-risk population. There are several ongoing trials, yet not concluded, that attempt to determine the usefulness of aspirin in primary prevention in high risk populations in order to clarify if there is a place in the employment of the aspirin in the primary prevention of ischemic heart disease.     

Surgical transvenous embolization of a cortically draining carotid cavernous fistula via a vein of the sylvian fissure

BACKGROUND AND PURPOSE: Although diabetes mellitus (DM) is known to increase the risk of cardiovascular disease (CVD), the effect of impaired glucose tolerance (IGT) on the risk remains unclear. We determined whether IGT was associated with an increased likelihood for stroke and myocardial infarction in a nationally representative sample of US adults. METHODS: We evaluated the association between IGT (defined as a fasting glucose level of < 140 mg/dL and a plasma glucose level of between 140 and 200 mg/dL 2 hours after administration of 75 grams of an oral glucose load) and DM (defined as the current use of insulin or an oral hypoglycemic medication, a fasting plasma glucose level of > 140 mg/dL, or a plasma glucose level of > 200 mg/dL 2 hours after administration of an oral glucose load) with a self-reported physician diagnosis of stroke and myocardial infarction in 6547 adults aged 40 to 74 years participating in the Third National Health and Nutrition Examination Survey. Multivariate logistic regression analyses were used to investigate these relationships. RESULTS: IGT and DM were observed in 1494 and 1532 adults, respectively. After adjustment for differences in age, gender, race/ethnicity, education, hypertension, cholesterol, body mass index, and cigarette smoking, IGT was not associated with stroke (odds ratio [OR], 0.9; 95% confidence interval [CI], 0.5 to 1.6) or myocardial infarction (OR, 1.1; 95% CI, 0.7 to 1.6). DM was associated with both stroke (OR, 1.6; 95% CI, 1.0 to 2.6) and myocardial infarction (OR, 1.9; 95% CI, 1.3 to 2.8). CONCLUSIONS: In contrast to DM, IGT was not associated with an increased likelihood of prevalent nonfatal stroke or myocardial infarction.     

Diuretic-based treatment and cardiovascular events in patients with mild renal dysfunction enrolled in the systolic hypertension in the elderly program

BACKGROUND: It is expected that the treatment of hypertension in patients with renal disease decreases the risk of cardiovascular events, but the evidence in these patients is lacking. OBJECTIVE: To assess the effect of diuretic-based treatment on cardiovascular events in patients with isolated systolic hypertension and renal dysfunction. METHODS: A total of 4336 persons aged 60 years and older with systolic blood pressures of 160 mm Hg and higher and diastolic blood pressures of less than 90 mm Hg were randomly assigned to receive either placebo or chlorthalidone (12.5-25.0 mg/d), with the addition of atenolol (25-50 mg/d) or reserpine (0.05-0.10 mg/d) if needed, and observed for 5 years. The risk of first-occurring cardiovascular events, including stroke, transient ischemic attack, myocardial infarction, heart failure, coronary artery bypass surgery, angioplasty, aneurysm, endarterectomy, sudden death, or rapid death, was stratified according to baseline serum creatinine levels (35.4-84.0, 84.1-101.6, 101.7-119.3, and 119.4-212.2 micromol/L [0.4-0.9, 1.0-1.1, 1.2-1.3, and 1.4-2.4 mg/dL]). RESULTS: Systolic blood pressure reduction was not affected by baseline serum creatinine levels. Active treatment did not affect the risk of serum creatinine levels becoming elevated during follow-up. The risk of hypokalemia with active treatment decreased significantly with increasing baseline serum creatinine levels. In the 4 baseline serum creatinine groups, the relative risk (95% confidence interval) of cardiovascular events developing with active treatment was 0.73 (0.54-0.97), 0.63 (0.49-0.82), 0.62 (0.44-0.87), and 0.59 (0.38-0.91). The results were similar for the outcomes of stroke or coronary artery events and in analyses stratified by sex or age. CONCLUSION: Diuretic-based treatment of patients with isolated systolic hypertension prevents the development of cardiovascular events in older persons with mild renal dysfunction.     

Human immunodeficiency virus infection and stroke in young patients

OBJECTIVE: To determine the association between human immunodeficiency virus (HIV) infection and stroke among young persons. DESIGN: Retrospective case-control study. SETTING: Large, inner-city public hospital. PARTICIPANTS: All patients aged 19 to 44 years with a diagnosis of stroke, whose HIV status was determined, admitted from January 1990 through June 1994. Controls matched for age and sex were selected from patients who were admitted during the same period for status asthmaticus whose HIV status was known. MAIN OUTCOME MEASURE: The associations of HIV infection with all strokes and with cerebral infarction, after adjustment for other cerebrovascular risk factors, were evaluated by Mantel-Haenszel stratified analyses. The subtypes and causes of stroke in HIV-infected patients were compared with HIV-seronegative patients. RESULTS: The HIV infection was associated with stroke (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.0-5.3) and cerebral infarction (OR, 3.4; 95% CI, 1.1-8.9), after adjustment for other cerebrovascular risk factors. Among patients with stroke, cerebral infarction was more frequent in HIV-infected patients than in HIV-seronegative patients (20 [80%] of 25 vs 48 [56%] of 88, P = .04). The frequency of cerebral infarctions associated with meningitis (P < .001) and protein S deficiency (P = .06) was higher in HIV-infected patients than in seronegative patients. CONCLUSIONS: Our study suggests that HIV infection is associated with an increased risk of stroke, particularly cerebral infarction in young patients. This risk is probably mediated by increased susceptibility of HIV-infected patients to meningitis and protein S deficiency.     

Econometric approaches to epidemiologic data: relating endogeneity and unobserved heterogeneity to confounding

BACKGROUND: In patients who have had a myocardial infarction, the long-term risk of stroke and its relation to the extent of left ventricular dysfunction have not been determined. We studied whether a reduced left ventricular ejection fraction is associated with an increased risk of stroke after myocardial infarction and whether other factors such as older age and therapy with anticoagulants, thrombolytic agents, or captopril affect long-term rates of stroke. METHODS: We performed an observational analysis of prospectively collected data on 2231 patients who had left ventricular dysfunction after acute myocardial infarction who were enrolled in the Survival and Ventricular Enlargement trial. The mean follow-up was 42 months. Risk factors for stroke were assessed by both univariate and multivariate Cox proportional-hazards analysis. RESULTS: Among these patients, 103 (4.6 percent) had fatal or nonfatal strokes during the study (rate of stroke per year of follow-up, 1.5 percent). The estimated five-year rate of stroke in all the patients was 8.1 percent. As compared with patients without stroke, patients with stroke were older (mean [+/-SD] age, 63+/-9 years vs. 59+/-11 years; P<0.001) and had lower ejection fractions (29+/-7 percent vs. 31+/-7 percent, P=0.01). Independent risk factors for stroke included a lower ejection fraction (for every decrease of 5 percentage points in the ejection fraction there was an 18 percent increase in the risk of stroke), older age, and the absence of aspirin or anticoagulant therapy. Patients with ejection fractions of < or = 28 percent after myocardial infarction had a relative risk of stroke of 1.86, as compared with patients with ejection fractions of more than 35 percent (P=0.01). The use of thrombolytic agents and captopril had no significant effect on the risk of stroke. CONCLUSIONS: During the five years after myocardial infarction, patients have a substantial risk of stroke. A decreased ejection fraction and older age are both independent predictors of an increased risk of stroke. Anticoagulant therapy appears to have a protective effect against stroke after myocardial infarction.     

Prospective study of calcium channel blocker use, cardiovascular disease, and total mortality among hypertensive women: the Nurses' Health Study

BACKGROUND: In several observational studies, patients prescribed calcium channel blockers had higher risks of cardiovascular diseases and mortality than those prescribed other antihypertensive medications. We explored these associations in the Nurses' Health Study. METHODS AND RESULTS: A total of 14 617 women who reported hypertension and regular use of diuretics, beta-blockers, calcium channel blockers, ACE inhibitors, or a combination in 1988 were included in the analyses. Cardiovascular events and deaths were ascertained through May 1, 1994. We documented 234 cases of myocardial infarction. Calcium channel blocker monodrug users had an age-adjusted relative risk (RR) of myocardial infarction of 2.36 (95% CI, 1.43 to 3.91) compared with those prescribed thiazide diuretics. Women prescribed calcium channel blockers had a higher prevalence of ischemic heart disease. After adjustment for these and other coronary risk factors, the RR was 1.64 (95% CI, 0.97 to 2.77). Comparing the use of any calcium channel blocker (monodrug and multidrug users) with that of any other antihypertensive agent, the adjusted RR was 1.42 (95% CI, 1.01 to 2.01). An association between calcium channel blocker use and myocardial infarction was apparent among women who had ever smoked cigarettes (covariate-adjusted RR, 1.81; 95% CI, 1.20 to 2.72) but not among never-smokers (RR, 0.94; 95% CI, 0.48 to 1.84). CONCLUSIONS: In analyses adjusted only for age, we found a significant elevation in RR of total myocardial infarction among women who used calcium channel blockers compared with those who did not. After adjustment for comorbidity and other covariates, the RR was reduced. Whether the remaining observed elevated risk is real, or a result of residual confounding by indication, or chance, or a combination of the above cannot be evaluated with certainty on the basis of these observational data.     

Reduction of recurrent ischemia with abciximab during continuous ECG-ischemia monitoring in patients with unstable angina refractory to standard treatment (CAPTURE)

BACKGROUND: In the CAPTURE (c7E3 Fab Anti Platelet Therapy in Unstable REfractory angina) trial, 1265 patients with refractory unstable angina were treated with abciximab or placebo, in addition to standard treatment from 16 to 24 hours preceding coronary intervention through 1 hour after intervention. To investigate the incidence of recurrent ischemia and the ischemic burden, a subset of 332 patients (26%) underwent continuous vector-derived 12-lead ECG-ischemia monitoring. METHODS and RESULTS: Patients were monitored from start of treatment through 6 hours after coronary intervention. Ischemic episodes were detected in 31 (18%) of the 169 abciximab and in 37 (23%) of the 163 placebo patients (NS). Only 9 (5%) of abciximab versus 22 (14%) of placebo patients had >/=2 ST episodes (P<0.01). In patients with ischemia, abciximab significantly reduced total ischemic burden (P<0.02), which was calculated alternatively as the total duration of ST episodes per patient, the area under the curve of the ST vector magnitude during episodes, or the sum of the areas under the curves of 12 leads during episodes. Twenty-one patients (6%) suffered a myocardial infarction (MI) (18) or died (3) within 5 days of treatment. The presence of asymptomatic and symptomatic ST episodes during the monitoring period preceding coronary intervention was associated with an increased relative risk of these events of 3.2 (95% CI 1.4, 7.4) and 4.1 (95% CI 1.4, 12.2), respectively. CONCLUSIONS: Recurrent ischemia predicts MI or death within 5 days of follow-up. Treatment with abciximab is associated with a reduction of frequent ischemia and a reduction of total ischemic burden in patients with refractory unstable angina. As such, patients with ischemia derive particularly high benefit from abciximab.     

Inverse association of dietary fat with development of ischemic stroke in men

CONTEXT: A few ecological and cohort studies in Asian populations suggest an inverse association of the intake of both fat and saturated fat with risk of stroke. However, data among western populations are scant. OBJECTIVE: To examine the association of stroke incidence with intake of fat and type of fat among middle-aged US men during 20 years of follow-up. DESIGN AND SETTING: The Framingham Heart Study, a population-based cohort study. PARTICIPANTS: A total of 832 men, aged 45 through 65 years, who were free of cardiovascular disease at baseline (1966-1969). MEASUREMENTS AND DATA ANALYSIS: The diet of each subject was assessed at baseline by a single 24-hour dietary recall, from which intakes of energy and macronutrients were estimated. In Kaplan-Meier analyses, we calculated age-adjusted cumulative incidence rates of stroke. Using Cox regression, we estimated stroke incidence relative risks during 20 years of follow-up. MAIN OUTCOME MEASURE: Incidence of ischemic stroke, which occurred in 61 subjects during the follow-up period. RESULTS: Mean intakes were 10975 kJ for energy; 114 g (39% of energy) for total fat; 44 g (15%) for saturated fat; 46 g (16%) for monounsaturated fat; and 16 g (5%) for polyunsaturated fat. Risk of ischemic stroke declined across the increasing quintile of total fat (log-rank trend P=.008), saturated fat (P=.002), and monounsaturated fat (P=.008) but not polyunsaturated fat (P=.33). The age- and energy-adjusted relative risk for each increment of 3% of energy from total fat was 0.85 (95% confidence interval [CI], 0.78-0.94); for an increment of 1% from saturated fat, 0.91 (95% CI, 0.85-0.98); and for 1% from monounsaturated fat, 0.89 (95% CI, 0.83-0.96). Adjustment for cigarette smoking, glucose intolerance, body mass index, blood pressure, blood cholesterol level, physical activity, and intake of vegetables and fruits and alcohol did not materially change the results. Too few cases of hemorrhagic stroke (n=14) occurred to draw inferences. CONCLUSION: Intakes of fat, saturated fat, and monounsaturated fat were associated with reduced risk of ischemic stroke in men.