Cerebrovascular disease.

With 16.9 million people who suffered a first-ever stroke in 2010 worldwide, stroke is a very common vascular disease. Epidemiologic studies have played an essential role in assessing this burden and in detecting the risk factors for stroke. Primary prevention of these risk factors, primarily hypertension, smoking, diabetes, and atrial fibrillation, has reduced the incidence in high-income countries. However, stroke remains a major cause of death and disability, and therefore research should be continued. Subarachnoid hemorrhages are less prevalent than strokes but have an even higher risk of death. Similar to stroke, epidemiologic studies identified smoking and hypertension as its most important risk factors, together with excessive alcohol intake. Although rare, arterial dissections, CADASIL, arteriovenous malformations, venous sinus thrombosis, moyamoya disease, and vasculitis can lead to serious symptoms. The burden and risk factors of those rare diseases are more challenging to assess. Whenever possible, they should be recognized in a timely manner for their increased risk of stroke, but most often they are diagnosed only at the time of stroke. Some cerebrovascular abnormalities do not result in immediate symptoms. This subclinical cerebrovascular disease includes silent infarcts, white-matter lesions, and microbleeds, and is incidentally found by neuroimaging. These lesions are not innocent, as several epidemiologic studies have associated subclinical cerebrovascular disease with an increased risk of stroke, cognitive decline, dementia, and death.

N-terminal pro-B-type natriuretic peptide and the risk of stroke and transient ischaemic attack: the Rotterdam Study.

BACKGROUND AND PURPOSE: Amino-terminal pro-B-type natriuretic peptide (NT-proBNP) is a predictor of heart disease. It has also been related to stroke, but its association with transient ischaemic attacks (TIAs) is unclear. Moreover, it is unknown how clinical heart disease influences this relation. Within the prospective population-based Rotterdam Study, the association of NT-proBNP with stroke and TIA was examined and the role of heart disease on this association was investigated. METHODS: NT-proBNP was measured in 1997-2001 in 5611 participants (mean age 68.7 years; 57.7% women) without a history of stroke, TIA or heart failure. Follow-up for stroke and TIA finished in 2012. Models were adjusted for age and cardiovascular risk factors, and were stratified by sex. RESULTS: During 22 058 person-years 195 men suffered a stroke and 118 a TIA. During 31 825 person-years 230 women suffered a stroke and 187 a TIA. Higher NT-proBNP was associated with a higher risk of stroke in men [hazard ratio (HR) per SD increase 1.50; 95% confidence interval (CI) 1.29-1.76] and in women (HR 1.24; 95% CI 1.05-1.46). Associations with TIA were only present in women (HR 1.51; 95% CI 1.26-1.82) but not in men (HR 1.02; 95% CI 0.83-1.26). Excluding persons with a history of clinical coronary heart disease, heart failure or atrial fibrillation and censoring for clinical heart disease during follow-up did not change the associations. CONCLUSIONS: Higher NT-proBNP is associated with incident stroke in men and women and with incident TIA only in women. These associations are independent of clinical heart disease preceding cerebrovascular disease.

Efficacy of metoprolol and diltiazem in treating silent myocardial ischemia.

Recent studies strongly support the prognostic importance of transient silent ischemia. Because patients with silent ischemia are at higher risk of a cardiac event, they are likely to benefit not only from control of symptoms, but also from treatment directed at prevention of ischemia. The efficacy of controlled-release metoprolol 200 mg once daily and diltiazem 60 mg 4 times daily was assessed in a randomized, double-blind, crossover study in 32 patients with proven coronary artery disease, predominantly asymptomatic myocardial ischemia, positive bicycle exercise test results, and > or = 5 minutes of asymptomatic ST-segment depression on a 24-hour screening ambulatory electrocardiogram (ECG). At the beginning and at the end of both 3-week treatment periods, an exercise test was performed and a 72-hour ambulatory ECG was recorded. Both active treatment periods were preceded by a 2-week placebo phase. Both treatments effectively reduced and postponed exercise-induced ST depression and reduced the total ischemic integral on the ambulatory ECG. Only metoprolol significantly reduced the mean number of ischemic episodes (54%, p = 0.0003, vs 31% for diltiazem, p = NS) and the mean duration of ischemia (51%, p = 0.012, vs 27% for diltiazem, p = NS) compared with baseline values. Metoprolol strongly blunted the morning and afternoon peak in the circadian distribution of ischemia, whereas diltiazem did not change the circadian distribution of ischemia at all.

Effect of isradipine and nifedipine on diastolic function in patients with left ventricular dysfunction due to coronary artery disease: a randomized, double-blind, nuclear, stethoscope study.

To elucidate the effect of isradipine and nifedipine on left ventricular (LV) systolic and diastolic function, each drug was given intravenously (i.v.) in equihypotensive doses to 10 patients accepted for coronary arteriography for stable angina pectoris. All 20 patients had LV ejection fraction (LVEF) of < 40% owing to previous myocardial infarction (MI). Systolic and diastolic function was assessed by standard hemodynamic parameters and pressure-volume relations measured by nuclear stethoscope. All measurements were taken at rest and during ischemia caused by right atrial pacing. Both systolic and diastolic parameters improved equally with isradipine and nifedipine. LVEF and cardiac output (CO) increased owing to peripheral vasodilatation. A decrease in P/Vmax, indicating a negative inotropic effect, was noted in patients at rest with both medications, but not during pacing-induced ischemia. With either medication, the time constant of relaxation and the end-diastolic elasticity constant decreased during pacing, indicating improvement in diastolic function, probably owing to relief of myocardial ischemia.

Lack of negative inotropic effects of the new calcium antagonist Ro 40-5967 in patients with stable angina pectoris.

We screened the antiischemic, hemodynamic, and inotropic effects of different dosages of the new calcium channel blocker Ro 40-5967 in 65 patients with stable effort-induced angina pectoris. In a double-blind way, patients were randomized to recieve a single oral dose of 50, 100, or 200 mg Ro 40-5967 or placebo, given as a drinking solution. Left ventricular ejection fraction (LVEF), blood pressure (BP), and heart rate (HR) were measured at rest and during a supine bicycle exercise test on day 0 (baseline) and 2 h after drug intake on day 1. Twenty-four hours later, the bicycle exercise test was repeated. Ro 40-5967 improved exercise duration and resting LVEF. After 200 mg, exercise time increased significantly from 8.4 +/- 0.8 min (mean +/- SEM) to 9.6 +/- 0.7 min (p = 0.018), and LVEF at rest increased from 54.5 +/- 2.2 to 58.1 +/- 2.6% (p = 0.045). Time to 0.1 mV ST-segment depression increased significantly from 4.3 +/- 0.8 to 5.5 +/- 0.9 min in the 100-mg group (p = 0.013) and from 4.3 +/- 1.3 to 5.4 +/- 1.5 min in the 200-mg group (p = 0.027). Maximum ST-segment depression decreased significantly at all dose levels (p = 0.01), with the maximum decrease noted in the 200-mg group (from 0.21 +/- 0.03 to 0.15 +/- 0.02 mV, p = 0.004). BP, HR, and rate-pressure product did not change significantly at rest or at maximum exercise. A single dose of Ro 40-5967 has antiischemic properties in patients with stable angina pectoris, with maximum effects obtained after 200 mg. No signs of negative inotropy were noted, and the drug was well tolerated.