Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The APOE varepsilon4 allele is associated with a variety of conditions such as Alzheimer's disease, coronary artery disease, stroke and postoperative cognitive dysfunction. The common pathophysiological feature that appears to explain these positive clinical associations with APOE varepsilon4 allele may relate to the decreased endogenous anti-oxidant capability of an individual. A significant body of existing clinical data supports the assumption that diseases associated with the varepsilon4 allele can be alleviated by antioxidant therapies, such as vitamin E. Therefore, we hypothesize that determination of an individual's APOE allele status has medical utility as an efficient method to identify patient subgroups susceptible to oxidative damage. We suggest that prospective studies are needed to determine if individuals at high risk for diseases characterized by oxidative damage and/or who have an APOE varepsilon4 allele might benefit significantly from available antioxidant intervention at a relatively early and asymptomatic age.
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PMID:Medical utility of apoe allele determination in assessing the need for antioxidant therapy. 1135 59

The Heart Outcomes Prevention Evaluation (HOPE) study was important because it showed the benefits of ramipril - an angiotensin-converting enzyme (ACE) inhibitor - in patients at high risk for cardiovascular events. Treatment with ramipril significantly reduced the rates of death, myocardial infarction, stroke, coronary revascularization, cardiac arrest and heart failure, as well as the risk of diabetes-related complications and of diabetes itself. The effects of therapy with vitamin E were also evaluated, but no statistical benefits were shown. The benefits of ACE inhibitor therapy that were observed were likely due to a variety of mechanisms, not just a reduction in blood pressure.
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PMID:Why were the results of the Heart Outcomes Prevention Evaluation (HOPE) trial so astounding? 1138 Dec 89

In spite of the decreasing trend in age-adjusted cardiovascular disease mortality in Western European countries, an increase in the cardiovascular morbidity is expected because of the ageing of the population. Consequently the health care cost for these diseases will increase. This article focuses on the role of diet in the occurrence of cardiovascular diseases. Total and HDL cholesterol are major determinants of coronary heart disease. Saturated and trans fatty acids have a total and LDL cholesterol elevating effect and unsaturated fatty acids a lowering effect. N-3 polyunsaturated fatty acids seem to have a protective effect on coronary heart disease occurrence independent of cholesterol. Dietary antioxidants could be of importance because they may prevent oxidation of the atherogenic cholesterol rich LDL lipoproteins. There is however no convincing evidence that either vitamin E, carotenoids or vitamin C protect against coronary heart disease. Observational research has shown that flavonols, polyphenols with strong antioxidant properties present in plant foods, may protect against coronary heart disease. Blood pressure is a major determinant of coronary heart disease and stroke. Historically salt is viewed as the most important dietary determinant of blood pressure. Recent research shows that also a low-fat diet rich in potassium, calcium and magnesium lowers blood pressure substantially. This suggests a multifactorial influence of different nutrients on blood pressure. It can be concluded that a diet low in saturated and trans fatty acids and rich in plant foods in combination with regular fish consumption is associated with a low risk of cardiovascular mortality.
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PMID:Diet and cardiovascular diseases. 1145 83

Multifactorial risk factor modification is proven to positively influence morbidity and mortality from both cardiovascular disease and stroke. The vascular endothelium has recently been a focus of interest in cardiovascular prevention. Data suggest that vascular endothelial dysfunction may contribute to the pathophysiology of clinical ischemia, especially angina, myocardial infarction, and sudden death. Endothelial dysfunction includes abnormalities of vasomotor tone (constriction and dilation), balance between fibrinolysis and thrombosis, control of the inflammatory response, and growth of vascular smooth muscle. Cardiovascular prevention interventions have been studied extensively and there are considerable data supporting a beneficial effect on endothelial dysfunction. The interventions that are clearly effective in improving endothelial function are diet and lipid-lowering therapy (especially with statin drugs), use of angiotensin-converting enzyme inhibitors, hormone replacement therapy, vitamin E, and proper physical exercise. Many challenging issues remain unsolved, however, and the endothelium at both the molecular and cellular levels must be further investigated for both research and clinical interests.
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PMID:Endothelial function and cardiovascular prevention: role of blood lipids, exercise, and other risk factors. 1152 Apr 52

Ascorbic acid (vitamin C) and alpha-tocopherol (vitamin E) have antioxidant properties that could improve redox-sensitive vascular changes associated with hypertension. We determined whether vitamins C and E influence vascular function and structure in hypertension by modulating activity of NADPH oxidase and superoxide dismutase (SOD). Adult stroke-prone spontaneously hypertensive rats (SHRSP) were divided into 3 groups: control (C; n=6), vitamin C-treated (vit C, 1000 mg/day; n=7), and vitamin E-treated (vit E, 1000 IU/day; n=8). All rats were fed 4% NaCl. Blood pressure was measured weekly. After 6 weeks of treatment, the rats were killed, and mesenteric arteries were mounted as pressurized preparations. Vascular O(2)(-) generation and NADPH oxidase activity were measured by chemiluminescence. Vascular SOD activity and plasma total antioxidant status (TAS) were determined spectrophotometrically. Blood pressure increased from 212+/-7 to 265+/-6 mm Hg in controls. Treatment prevented progression of hypertension (vit C, 222+/-6 to 234+/-14 mm Hg; vit E, 220+/-9 to 227+/-10 mm Hg). Acetylcholine-induced vasodilation was improved (P<0.05), and media-to-lumen ratio was reduced (P<0.05) in the treated rats. O(2)(-) was lower in vitamin-treated groups compared with controls (vit C, 10+/-4 nmol. min(-1). g(-1) dry tissue weight; vit E, 9.6+/-3.5 nmol. min(-1). g(-1) dry tissue weight; C, 21+/-9 nmol. min(-1). g(-1) dry tissue weight; P<0.05). Both vitamin-treated groups showed significant improvement (P<0.01) in TAS. These effects were associated with decreased activation of vascular NADPH oxidase (vit C, 46+/-10; vit E, 50+/-9; C, 70+/-16 nmol. min(-1). g(-1) dry tissue weight, P<0.05) and increased activation of SOD (vit C, 12+/-2; vit E, 8+/-1; C, 4.6+/-1 U/mg; P<0.05). Our results demonstrate that vitamins C and E reduce oxidative stress, improve vascular function and structure, and prevent progression of hypertension in SHRSP. These effects may be mediated via modulation of enzyme systems that generate free radicals.
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PMID:Antioxidant effects of vitamins C and E are associated with altered activation of vascular NADPH oxidase and superoxide dismutase in stroke-prone SHR. 1156 40

Within Europe large differences exist in mortality from coronary heart disease and stroke. These diseases show a clear West-East gradient with high rates in Eastern Europe. In spite the decreasing trend in age-adjusted cardiovascular disease mortality in Western European countries an increase in the number of cardiovascular patients is expected because of the ageing of the population. Consequently the health care cost for these diseases will increase. Total and HDL cholesterol are major determinants of coronary heart disease. Saturated and trans fatty acids have a total and LDL cholesterol elevating effect and unsaturated fatty acids a lowering effect. N-3 polyunsaturated fatty acids seem to have a protective effect on coronary heart disease occurrence independent of their effect on cholesterol. Dietary antioxidants could be of importance because they may prevent oxidation of the atherogenic cholesterol rich LDL lipoproteins. There is however no convincing evidence that either vitamin E, carotenoids or vitamin C protect against coronary heart disease. Observational research has shown that flavonols, polyphenols with strong antioxidant properties present in plant foods, may protect against coronary heart disease. Blood pressure is a major determinant of coronary heart disease and stroke. Historically salt is viewed as the most important dietary determinant of blood pressure. Recent research shows that also a low-fat diet rich in potassium, calcium and magnesium lowers blood pressure substantially. This suggests a multifactorial influence of different nutrients on blood pressure. It can be concluded that a diet low in saturated and trans fatty acids and rich in plant foods in combination with regular fish consumption is associated with a low risk of cardiovascular mortality.
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PMID:Epidemiology of cardiovascular diseases in Europe. 1168 40

Over a 4.5 year follow-up period, the HOPE (Heart Outcomes Prevention Evaluation) trial, and the MICRO-HOPE (Microalbuminuria, Cardiovascular, and Renal Outcomes) and SECURE (Study to Evaluate Carotid Ultrasound changes in patients treated with Ramipril and vitamin E) substudies have all demonstrated a large benefit of ramipril versus placebo in patients over 55 years at high risk (by reason of a prior vascular event), or by being diabetic subjects with one additional risk factor. The baseline blood pressure on average was normal, at 139/79 mmHg, and was modestly reduced by 3.3/1.4 mmHg. Patients with known left ventricular dysfunction were excluded, as were those with uncontrolled hypertension. The incidence of stroke was reduced by 32%, myocardial infarction by 20% and cardiovascular death by 25%. The benefits conferred were in addition to, and largely independent of, other conventional treatments such as aspirin, lipid-lowering agents, beta-blockers, diuretics and calcium channel blockers. The relative risk reduction was very similar whether or not the patient was a known hypertensive at baseline. High dose ACE inhibition with ramipril is applicable to a far wider population of patients at high risk of cardiovascular events than the current indications of hypertension and left ventricular dysfunction.
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PMID:Future perspectives and implications. 1171 55

The preventive effects of sesamin, a lignan from sesame oil, and vitamin E on hypertension and thrombosis were examined using stroke-prone spontaneously hypertensive rats (SHRSP). At 5 weeks of age the animals were separated into four groups: (i) a control group; (ii) a vitamin E group, which was given a 1,000 mg alpha-tocopherol/kg diet; (iii) a sesamin group, given a 1,000 mg sesamin/kg diet; and (iv) a vitamin E plus sesamin group, given a 1,000 mg alpha-tocopherol plus 1,000 mg sesamin/kg diet for 5 weeks from 5 to 10 weeks of age. Resting blood pressure was measured by the tail-cuff method once weekly. A closed cranial window was created and platelet-rich thrombi were induced in vivo using a helium-neon laser technique. The number of laser pulses required for formation of an occlusive thrombus was used as an index of thrombotic tendency. In control rats, systolic blood pressure and the amount of urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) became significantly elevated with age. However, the elevation in blood pressure and 8-OHdG were significantly suppressed in rats administrated vitamin E, sesamin, or vitamin E plus sesamin. At 10 weeks, the number of laser pulses required to induce an occlusive thrombus in arterioles of the control group was significantly lower than in the other groups (p<0.05). These results indicate that chronic ingestion of vitamin E and sesamin attenuated each of elevation in blood pressure, oxidative stress and thrombotic tendency, suggesting that these treatments might be beneficial in the prevention of hypertension and stroke.
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PMID:Effects of vitamin E and sesamin on hypertension and cerebral thrombogenesis in stroke-prone spontaneously hypertensive rats. 1176 36

Recent studies indicate that there is an interaction between biorhythms, the biological clock and triggers, which may be important in the pathogenesis of altered heart rate variability (HRV) and blood pressure variability (BPV). Circadian rhythms are under the influence of, and physiological variables are mediated by the activation of the adrenals, sympathetic/parasympathetic, hypothalamic and pituitary activity. Emotional stress, physical exertion, sleep deprivation and large fatty meals are major triggers of myocardial ischemia, angina, infarction, sudden cardiac death (SCD) and stroke. These events have been reported to exhibit a circadian variation with increased frequency in the second quarter of the day, which has also been observed in our studies on Indians. Recent studies indicate that altered HRV and BPV are also important in the pathogenesis and progression of heart failure, atheroma and thrombosis. Mediation via beta-blockers, oestrogens, n-3 fatty acids, vitamin E and coenzyme Q10 and fasting appears to have a beneficial influence whereas progestins, nifedipine, stress and exercise may have an adverse effect on HRV and BPV. We have reported that plasma levels of vitamin E and C are lower in the second quarter of the day than at other times, indicating their role in the pathogenesis of variability and cardiac events. Prospective studies also indicate that HRV and BPV are important and independent risk factors for cardiovascular events. However, no study has yet been conducted in patients with abnormal HRV and BPV in a randomized, placebo-controlled intervention trial to find out whether improvement in variability can cause a significant reduction in cardiovascular events. There is a need to study the role of n-3 fatty acids, coenzyme Q10, the effect of regular physical training, medication and ACE inhibitors in patients with abnormal HRV and BPV to demonstrate that improving variability can modulate cardiovascular events.
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PMID:Can nutrition influence circadian rhythm and heart rate variability? 1177 58

Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardio (GISSI)-Prevenzione was conceived as a population, pragmatic trial on patients with recent myocardial infarctions conducted in the framework of the Italian public health system. In GISSI-Prevenzione, patients were invited to follow Mediterranean dietary habits, and were treated with up-to-date preventive pharmacological interventions. Long-term n-3 PUFA (1 g daily) but not vitamin E (300 mg daily) was beneficial for death and for combined death, nonfatal myocardial infarction, and stroke. All the benefit, however, was attributable to the decrease in risk for overall, cardiovascular, cardiac, coronary, and sudden death. At variance with the orientation of a scientific scenario largely dominated by the "cholesterol-heart hypothesis," GISSI-Prevenzione results indicate n-3 PUFA (virtually devoid of any cholesterol-lowering effect) as a relevant pharmacological treatment for secondary prevention after myocardial infarction. As to the relevance and comparability of GISSI-Prevenzione results, up to 5.7 lives could be saved every 1000 patients with previous myocardial infarction treated with n-3 PUFA (1 g daily) per year. Such a result is comparable to that observed in the Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) trial, where 5.2 lives could be saved per 1000 hypercholesterolemic, coronary heart disease patients treated with pravastatin for 1 yr. The choice of a relatively low-dose regimen (1-g capsule daily) more acceptable for long-term treatment in a population of patients following Mediterranean dietary habits, and the pattern of effects seen in GISSI-Prevenzione (namely, reduction of overall mortality with no decrease in the rate of nonfatal myocardial infarction) all strongly suggest that n-3 PUFA treatment should be considered a recommended new component of secondary prevention. The importance of this combined/additive effect is further suggested by the analyses of the interplay between diet and n-3 PUFA: There is an interesting direct correlation between size of the effect and "correctness" of background diets. It can be anticipated that a conceptual barrier must be overcome: A "dietary drug" should be added to "dietary advice," which remains fundamental to allow this statement to become true in clinical practice.
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PMID:Efficacy of n-3 polyunsaturated fatty acids after myocardial infarction: results of GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico. 1183 85


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