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April 2005

Long term risks of stroke, myocardial infarction, and vascular death in “low risk” patients with a non-recent transient ischaemic attack.

BACKGROUND: Previous studies of prognosis after a transient ischaemic attack (TIA) have recruited patients soon after the event, when the risk of stroke is very high. However, the majority of patients survive for many years after a TIA, and the need for continued preventive treatment to lower vascular risk will need to be reassessed at a later date. OBJECTIVE: To determine the long term risks of stroke and other vascular events in patients with TIA who survive the initial high risk period. METHODS: 290 patients were studied who had initially been followed up after a TIA in the Oxford community stroke project and in a contemporaneous hospital based cohort study, and who were alive and stroke-free at the end of planned follow up in 1988. All patients were followed for a further 10 years, and the risks of major vascular events (stroke, myocardial infarction, vascular death) were determined. Standardised mortality ratios (SMR) were calculated from the observed numbers of fatal events and the number expected on the basis of age and sex in the general population. RESULTS: Median time since last TIA was 3.8 years (interquartile range, 2.2 to 5.8 years). The risk of major vascular events was constant through time. The 10 year risk of first stroke was 18.8% (95% confidence interval (CI), 13.6 to 23.7; 45 events). The 10 year risk of myocardial infarction or death from coronary heart disease was 27.8% (95% CI, 21.8 to 33.3; 67 events) and there was a significant excess of fatal coronary events compared with that expected in the general population (SMR = 1.47; 95% CI, 1.10 to 1.93; p = 0.009). A total of 114 patients had at least one major vascular event, with a 10 year risk of any first stroke, myocardial infarction, or vascular death of 42.8% (95% CI, 36.4 to 48.5). CONCLUSIONS: The overall risk of major vascular events remains high for 10 to 15 years after a TIA. It is important therefore that preventive treatments are continued in the long term, even in apparently “low risk” patients who have already survived free of stroke for several years.

J Neurol Neurosurg Psychiatry. 2003 May;74(5):577-80

Comparison between measures of atherosclerosis and risk of stroke: the Rotterdam Study.

BACKGROUND AND PURPOSE: Several measures of atherosclerosis predict the risk of stroke. However, a comparison between various measures of atherosclerosis is lacking, and limited information exists on the added value of individual measures of atherosclerosis to cardiovascular risk factors. We compared different measures of atherosclerosis in relation to stroke. METHODS: The study was based on the prospective cohort of the Rotterdam Study and included 6,913 participants who did not suffer from previous stroke. At baseline, carotid intima-media thickness and plaques, ankle-arm index, and aortic calcifications were assessed; 3,996 participants (53%) had measures of all studied markers of atherosclerosis. After a mean follow-up of 6.1 years, 378 strokes occurred. Data were analyzed with Cox proportional-hazards regression and Akaike information criteria scores. RESULTS: Carotid intima-media thickness and aortic calcifications were related most strongly to the risk of stroke (relative risk, 2.23 and 1.89; 95% confidence interval, 1.48 to 3.36 and 1.28 to 2.80 for highest versus lowest tertile, respectively). The relations between intima-media thickness, aortic calcifications, and carotid plaques and stroke remained after adjustment for cardiovascular risk factors. Intima-media thickness and aortic calcifications were related to the risk of stroke independently of each other. The relation between ankle-arm index and stroke disappeared after adjustment for cardiovascular risk factors. CONCLUSIONS: Carotid intima-media thickness and aortic calcifications are stronger predictors of incident stroke than carotid plaque or ankle-arm indexes. They have additional value to each other and to classic risk factors and may reflect different processes.

Stroke. 2003 Oct;34(10):2367-72. Epub 2003 Sep 04

The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report.

“The Seventh Report of the Joint National Committee on Preven-tion, Detection, Evaluation, and Treatment of High Blood Pressure” provides a new guideline for hypertension prevention and management. The following are the key messages(1) In persons older than 50 years, systolic blood pressure (BP) of more than 140 mm Hg is a much more important cardiovascular disease (CVD) risk factor than diastolic BP; (2) The risk of CVD, beginning at 115/75 mm Hg, doubles with each increment of 20/10 mm Hg; individuals who are normotensive at 55 years of age have a 90% lifetime risk for developing hypertension; (3) Individuals with a systolic BP of 120 to 139 mm Hg or a diastolic BP of 80 to 89 mm Hg should be considered as prehypertensive and require health-promoting lifestyle modifications to prevent CVD; (4) Thiazide-type diuretics should be used in drug treatment for most patients with uncomplicated hypertension, either alone or combined with drugs from other classes. Certain high-risk conditions are compelling indications for the initial use of other antihypertensive drug classes (angiotensin-converting enzyme inhibitors, angio-tensin-receptor blockers, beta-blockers, calcium channel blockers); (5) Most patients with hypertension will require 2 or more antihypertensive medications to achieve goal BP (<140/90 mm Hg, or <130/80 mm Hg for patients with diabetes or chronic kidney disease); (6) If BP is more than 20/10 mm Hg above goal BP, consideration should be given to initiating therapy with 2 agents, 1 of which usually should be a thiazide-type diuretic; and (7) The most effective therapy prescribed by the most careful clinician will control hypertension only if patients are motivated. Motivation improves when patients have positive experiences with and trust in the clinician. Empathy builds trust and is a potent motivator. Finally, in presenting these guidelines, the committee recognizes that the responsible physician’s judgment remains paramount.

JAMA. 2003 May 21;289(19):2560-72

Effect of antihypertensive agents on cardiovascular events in patients with coronary disease and normal blood pressure: the CAMELOT study: a randomized controlled trial.

CONTEXT: The effect of antihypertensive drugs on cardiovascular events in patients with coronary artery disease (CAD) and normal blood pressure remains uncertain. OBJECTIVE: To compare the effects of amlodipine or enalapril vs placebo on cardiovascular events in patients with CAD. DESIGN, SETTING, AND PARTICIPANTS: Double-blind, randomized, multicenter, 24-month trial (enrollment April 1999-April 2002) comparing amlodipine or enalapril with placebo in 1991 patients with angiographically documented CAD (>20% stenosis by coronary angiography) and diastolic blood pressure <100 mm Hg. A substudy of 274 patients measured atherosclerosis progression by intravascular ultrasound (IVUS). INTERVENTIONS: Patients were randomized to receive amlodipine, 10 mg; enalapril, 20 mg; or placebo. IVUS was performed at baseline and study completion. MAIN OUTCOME MEASURES: The primary efficacy parameter was incidence of cardiovascular events for amlodipine vs placebo. Other outcomes included comparisons of amlodipine vs enalapril and enalapril vs placebo. Events included cardiovascular death, nonfatal myocardial infarction, resuscitated cardiac arrest, coronary revascularization, hospitalization for angina pectoris, hospitalization for congestive heart failure, fatal or nonfatal stroke or transient ischemic attack, and new diagnosis of peripheral vascular disease. The IVUS end point was change in percent atheroma volume. RESULTS: Baseline blood pressure averaged 129/78 mm Hg for all patients; it increased by 0.7/0.6 mm Hg in the placebo group and decreased by 4.8/2.5 mm Hg and 4.9/2.4 mm Hg in the amlodipine and enalapril groups, respectively (P<.001 for both vs placebo). Cardiovascular events occurred in 151 (23.1%) placebo-treated patients, in 110 (16.6%) amlodipine-treated patients (hazard ratio [HR], 0.69; 95% CI, 0.54-0.88 [P = .003]), and in 136 (20.2%) enalapril-treated patients (HR, 0.85; 95% CI, 0.67-1.07 [P = .16]. Primary end point comparison for enalapril vs amlodipine was not significant (HR, 0.81; 95% CI, 0.63-1.04 [P = .10]). The IVUS substudy showed a trend toward less progression of atherosclerosis in the amlodipine group vs placebo (P = .12), with significantly less progression in the subgroup with systolic blood pressures greater than the mean (P = .02). Compared with baseline, IVUS showed progression in the placebo group (P<.001), a trend toward progression in the enalapril group (P = .08), and no progression in the amlodipine group (P = .31). For the amlodipine group, correlation between blood pressure reduction and progression was r = 0.19, P = .07. CONCLUSIONS: Administration of amlodipine to patients with CAD and normal blood pressure resulted in reduced adverse cardiovascular events. Directionally similar, but smaller and nonsignificant, treatment effects were observed with enalapril. For amlodipine, IVUS showed evidence of slowing of atherosclerosis progression.

JAMA. 2004 Nov 10;292(18):2217-25

Body mass index in mid-life is associated with a first stroke in men: a prospective population study over 28 years.

BACKGROUND AND PURPOSE: Data on the association between obesity and stroke are still limited. We examined the possible association between mid-life body mass index (BMI) and risk of stroke in the prospective Multifactor Primary Prevention Study in Goteborg, Sweden. METHODS: 7,402 apparently healthy men aged 47 to 55 at baseline were followed-up over a 28-year period. Incidence of fatal and nonfatal stroke was recorded in a local stroke registry through the Swedish National Register on Cause of Death and the Swedish Hospital Discharge Registry. RESULTS: A total of 873 first strokes were recorded, including 495 ischemic, 144 hemorrhagic, and 234 unspecified strokes. Compared with men with low normal weight (BMI, 20.0 to 22.49 kg/m2), men with BMI >30.0 kg/m2 had a multiple adjusted hazard ratio of 1.93 (95% CI, 1.44 to 2.58) for total stroke, 1.78 (95% CI, 1.22 to 2.60) for ischemic stroke, and 3.91 (95% CI, 2.10 to 7.27) for unspecified stroke. There was no significant association between BMI and hemorrhagic stroke. Adjustment for potential mediators, eg, hypertension, diabetes and serum cholesterol levels, attenuated but did not eliminate the risk. CONCLUSIONS: In this prospective population-based study of men, increased BMI in mid-life was associated with an increased risk for total, ischemic, and unspecified stroke, but not with hemorrhagic stroke. The result supports the role of mid-life BMI as a risk factor for stroke later in life and suggests a differentiated effect on stroke subtypes.

Stroke. 2004 Dec;35(12):2764-9

Apolipoprotein B/apolipoprotein A-I in relation to the metabolic syndrome and change in carotid artery intima-media thickness during 3 years in middle-aged men.

BACKGROUND AND PURPOSE: The apolipoprotein B (apoB)/apolipoprotein A-I (apoA-I) ratio is a measure of the relationship between different lipoprotein particles and a powerful predictor of coronary death. The aim was to examine whether apoB/apoA-I was associated with the metabolic syndrome (MetS) at baseline and also with the future change in carotid artery intima-media thickness (IMT). METHODS: In 313 58-year-old men, carotid artery IMT was measured bilaterally by high-resolution B-mode ultrasound at baseline and after 3 years of follow-up. Serum apolipoprotein concentrations and the components of MetS were measured at study entry. RESULTS: ApoB/apoA-I showed statistically significant associations with body mass index, waist-to-hip ratio, high-density lipoprotein (HDL) cholesterol, triglycerides, low-density lipoprotein (LDL) particle size, insulin, and diastolic blood pressure. Two thirds of the patients with MetS had high apoB/apoA-I ratios (>0.90) compared with one third of those without the syndrome (P<0.001). The IMT change was associated with apoB, total cholesterol, LDL cholesterol, triglycerides, and inversely with HDL cholesterol and LDL particle size at entry, and there was a strong colinearity between these variables. The subjects with apoB/apoA-I above the first tertile (0.74) had a 20-microm-higher (95% CI, 7 to 33) annual increase in IMT compared with those below this level after adjustment for blood pressure and smoking. CONCLUSIONS: The apoB/apoA-I ratio was strongly associated with MetS and its components at baseline. ApoB/apoA-I at baseline was related to the change in carotid artery IMT during 3 years of follow-up. There was a strong colinearity between apoB/apoA and the atherogenic lipids.

Stroke. 2004 Oct;35(10):2248-5