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PubMed2007

Molecular targets for retinal vascular diseases.

The elucidation of the molecular pathogenesis of a disease in animal models provides candidate targets for treatment. As specific antagonists for a target are developed and tested in clinical trials, if benefit is achieved, the candidate becomes a validated target. Validated targets stimulate additional research to identify optimal ways of attacking the target and studies in related disease processes to determine if the molecule is also a target in that context. Vascular endothelial growth factor (VEGF) has been identified as a validated target for several retinal vascular diseases. This has led to a flurry of activity resulting in beneficial treatments for patients and intensification of the search for other targets. This review summarizes preclinical and clinical trial results obtained with VEGF antagonists and describes evidence supporting the candidacy of other molecules currently being tested or soon to be tested for target status.

Animals↗
PubMed1999

Homocysteine levels in healthy New Zealanders and those with vascular disease.

AIMS: Levels of plasma homocysteine (tHcy) have been shown to vary between populations. The aim of the present study was to determine tHcy levels in a New Zealand population to facilitate interpretation of international reference ranges. METHODS: Fasting tHcy levels were determined in 431 volunteer men and women, aged between 17 and 83 years, from the greater Otago region. Subjects with self-reported incidences of vascular disease (n=138) were compared with healthy control subjects (n=293). RESULTS: Mean (SD) fasting tHcy level of the entire population was 8.3(3.5) micromol/L and men had significantly higher levels than women (9.0(3.4) and 7.8(3.5) micromol/L, respectively, p<0.05). Levels increased significantly with increasing age (0.5 micromol/L for every ten years). There was a small but non-significant difference in tHcy levels between subjects with and without vascular disease (difference after excluding two outliers and adjusting for age and gender; 0.63, 95% CI, -0.03,1.29). tHcy levels were not significantly correlated with lipid or lipoprotein levels. CONCLUSION: Levels of tHcy in a group of volunteers from the greater Otago region were similar to those reported in other populations at high risk of cardiovascular disease. Reference ranges derived from these populations would appear to be applicable for New Zealanders. tHcy measurements should be made when assessing individuals at high risk of vascular disease and intervention strategies considered.

Adolescent↗
PubMed1985

Hypertriglyceridemia in insulin dependent diabetes mellitus with peripheral vascular disease.

Hypertriglyceridemias are the most frequent lipid disorders in diabetes mellitus with peripheral vascular disease. In spite of increasing knowledges the arteriosclerotic risk of hypertriglyceridemias is still controversial. In 77 insulin dependent diabetes (IDDM) (23 m, 54 f, age: 52 +/- 18 y. body weight: 119 +/- 21% to Brocal) with hypertriglyceridemia (TG greater than or equal to 200 mg/dl) and 97 IDDM (39 m, 68 f, age: 47 +/- 18 y, body weight: 116 +/- 22% to Broca) without lipid disorders (TG less than 200 mg/dl, CH less than 260 mg/dl) we investigated whether measurement of lipoprotein-lipids is better indicator of arteriosclerotic risk than total triglycerides. Peripheral vascular diseases (PVD) were present in 45% of patients with HTG and in 32% of patients without lipid disorders. In both groups patients with PVD had lower HDL-cholesterol (p less than 0.05 resp. p less than 0.0005) and higher VLDL-cholesterol (p less than 0.025 resp. p less than 0.005). A negative relationship between VLDL-cholesterol and HDL-cholesterol was only significant in IDDM without lipid disorders (p less than 0.001). Considering a ratio of VLDL/HDL-cholesterol of greater than or equal to 1.0 resp. less than 1.0 to be discriminating for patients with or without PVD 65.1% of all PVD (specifity) and 60.7% of all Non-PVD (sensitivity) could be correctly characterized. It is concluded, that in IDDM the ratio of VLDL/HDL-cholesterol is a better indicator for the arteriosclerotic risk than total triglycerides or total cholesterol.

Adult↗
PubMed1996

The long-term effect of eicosapentaenoic acid on serum levels of lipoprotein (a) and lipids in patients with vascular disease.

The effects of eicosapentaenoic acid (EPA) on serum lipoprotein (a) (Lp(a)) and other lipid levels in patients with vascular disease were examined. The serum levels of Lp(a), total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL) and very-low-density lipoprotein (VLDL) were measured in 24 patients with vascular disease. An elevated serum Lp(a) level (39 +/- 22 mg/dl) was noted in 9 patients, elevated total cholesterol level (263 +/- 31 mg/dl) in 12 patients, elevated triglyceride level (240 +/- 98 mg/dl) in 10 patients and elevated LDL level (651 +/- 88 mg/dl) in 6 patients before administration of EPA. EPA (1,800 mg/day) was given to these patients for long periods ranging from 6 to 24 months. The serum levels of Lp(a), TC, TG and LDL were lowered significantly (p < 0.05) after EPA administration for 12 and 18 months, for 6, 12, 18 and 24 months, for 18 months and for 12 and 18 months, respectively. These findings indicated that long-term administration of EPA may lower Lp(a) and serum lipids, which is beneficial for patients with various arterial diseases in terms of preventing progression of the disease.

Administration, Oral↗
PubMed1976

Fibrinogen heterogeneity in cancer, in occlusive vascular disease, and after surgical procedures.

Electrophoresis in 3.5% polyacrylamide gel was used to determine the patterns of fibrinogen heterogeneity in healthy subjects, in postoperative patients and in patients with cancer or occlusive vascular disease. Two major and one minor fibrinogen fractions, differing in molecular weight, were identified, and their concentrations in blood determined. The high-molecular-weight (HWM) fraction was found in greatest concentration after operation, during the period of hyperfibrinogenemia, whereas no simultaneous increase of lower-molecular-weight (LMW and LMW') fractions occurred, suggesting that these were derivatives of HMW ("native") fibrinogen. No correlation between the concentrations of the LMW and LMW' fractions and fibrinolytic activity was found, suggesting that direct degradation of HMW fibrinogen by plasmin was unlikely. The high fibrinogen level in cancer patients was related to increased concentrations of HMW and LMW fractions, whereas in the vascular-disease patients it was due exclusively to increased concentrations of LMW and LMW' fibrinogen. Serial observations indicated little fluctuation in the concentration of these fractions, indicating a persistently accelerated rate of conversion of HMW to LMW and LMW' fibrinogen in occlusive vascular disease. Possible pathogenic implications are discussed.

Adult↗
PubMed2000

The Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) trial programme; rationale, design and baseline characteristics including a meta-analysis of the effects of thienopyridines in vascular disease.

BACKGROUND: Other than aspirin, there are few oral antithrombotic treatments with proven efficacy in patients with acute coronary syndrome. In this report, we present the rationale, design and baseline characteristics of the Clopidogrel in Unstable angina to prevent Recurrent ischaemic Events (CURE) trial, which includes a meta-analysis of the effects of thienopyridines in patients with vascular disease. METHODS AND RESULTS: Combined data from randomized trials of thienopyrindines in patients with atherosclerotic disease demonstrated a 29% reduction in vascular events when compared with placebo/control (n=2392) (OR 0.71, 95% CI 0.58-0.86, P=0.0006) and a 10% reduction in vascular events when compared with aspirin (n=22 254) (OR 0.91, 95% Cl 0.84-0.99, P=0.039). Similarly, randomized trials of aspirin plus thienopyridines in patients undergoing intracoronary stenting, demonstrated a marked benefit of aspirin plus ticlopidine in reducing death or myocardial infarction compared with aspirin alone (OR 0.23, 95% CI 0.11-0.49, P=0.0001) or aspirin plus warfarin (OR 0.51, 95% CI 0.33-0.78, P=0.002). Whether these benefits extend to the much larger population of patients with acute coronary syndrome is unknown. CURE is an international, randomized, double-blind trial, in which patients with acute coronary syndrome will be randomized to receive either a bolus dose of clopidogrel (300 mg) followed by 75 mg per day for 3-12 months, or matching placebo. Both groups will receive aspirin. The co-primary efficacy end-points of CURE are: (1) the composite of cardiovascular death, myocardial infarction or stroke; and (2) the composite of cardiovascular death, myocardial infarction, stroke or refractory ischaemia. CURE will recruit approximately 12 500 patients with acute coronary syndrome (from 28 countries) and its power to detect moderate treatment benefits will be in the region of 80-90%, while maintaining an overall type I error (alpha) of 0.05. The baseline characteristics of the study population are consistent with at least a moderate risk group of patients with acute coronary syndrome. CONCLUSIONS: Randomized trials of thienopyridines in patients with vascular disease demonstrate that thienopyridines are effective in reducing vascular events when compared with placebo/control or aspirin, as well as when used in combination with aspirin in patients undergoing intracoronary stent implantation. The CURE trial is a large international study to determine if acute and long-term treatment with the combination of clopidogrel and aspirin is superior to aspirin alone in patients with acute coronary syndrome.

Angina, Unstable↗
PubMedDate not supplied

Homocysteine and vascular disease.

For more than 20 years, moderately raised concentrations of total homocysteine have been associated with an increased risk of atherothrombotic vascular events but only recently has evidence mounted to suggest that the association may be causal. The association is independent of other factors, it is fairly consistent across many studies, it is strong and dose-related, and it is biologically plausible. However, the evidence needs to be strengthened by a systematic review of all comparable studies and the demonstration, in randomised trials, that lowering total homocysteine is followed by a significant reduction in atherothrombotic vascular disease. In addition, the measurement of total homocysteine needs to be standardised. If these can be achieved then total homocysteine measurement will become another useful marker of vascular risk, multivitamin therapy will be another therapeutic option for people at risk of atherothrombotic vascular disease, and fortification of food with folic acid will rise high on the political and public health agenda.

Homocysteine↗
PubMed2002

[Changes of both knowledge levels and health-related behaviors of preventing cardio-cerebro-vascular diseases in population after intervention].

Comprehensive intervention measures for preventing cardio-cerebro-vascular diseases of community population were carried out in Beijing, Shanghai and Changsha urban areas, and then was evaluated to its effects on knowledge, attitude and behavior (KAB) levels and health-related behaviors of population by quasi-trial designation. Results showed that the net KAB leveling were separately 9.89 in 1995, 4.74 in 1997 and 10.66 in 2000 in comparison with base investigation, and statistically significant difference was found. Of 6 health-related behaviors, caring to health knowledge, being influenced by health knowledge and exercising were significantly influenced, next controlling salt consumption. No change of smoking and alcohol drinking was found. Among different target population, these changes among women were higher than man as well as at home or retired than at work, and hypertension than normtension. As aging and education time decreasing, both absolute and relative effects of health education were better. It suggests that comprehensive intervention with health education as its main measure promote KAB levels and transfer health-related behaviors of population. It is great important to preventing cardio-cerebro-vascular diseases of community population.

Adult↗