enalapril and Hemorrhage

Identification of novel risk factors is needed to further lower stroke risk. Data concerning the association between plasma retinol concentrations and the risk of stroke are limited.. We aimed to evaluate the effect of plasma retinol on the risk of first stroke and to examine any possible effect modifiers in hypertensive patients.. The study sample population was drawn from the China Stroke Primary Prevention Trial (CSPPT), using a nested case-control design, including 620 cases with first stroke and 620 matched controls. In the CSPPT, a total of 20,702 hypertensive patients were randomly assigned to a double-blind, daily treatment with either 10 mg enalapril and 0.8 mg folic acid or 10 mg enalapril alone. The median treatment duration was 4.5 y.. There was a significant inverse association between plasma retinol and the risk of first stroke (per 10-μg/dL increment; OR: 0.92; 95% CI: 0.86, 0.97) and first ischemic stroke (OR: 0.92; 95% CI: 0.86, 0.98). When retinol was assessed as quartiles, significantly lower risks of first stroke (OR: 0.64; 95% CI: 0.46, 0.88) and first ischemic stroke (OR: 0.67; 95% CI: 0.46, 0.96) were found in participants in quartiles 2-4 compared with those in quartile 1. Furthermore, a stronger inverse association between plasma retinol and first stroke was observed in participants with baseline total homocysteine (<10 compared with ≥10 μmol/L; P-interaction = 0.049). However, plasma retinol had no significant effect on first hemorrhagic stroke (per 10-μg/dL increment; OR: 0.98; 95% CI: 0.79, 1.18).. Our data showed a significant inverse association between plasma retinol and the risk of first stroke among Chinese hypertensive adults. This study was registered at clinicaltrials.gov as NCT00794885.

Topics: Aged; Antihypertensive Agents; Brain Ischemia; Case-Control Studies; China; Double-Blind Method; Enalapril; Female; Folic Acid; Hemorrhage; Homocysteine; Humans; Hypertension; Male; Middle Aged; Odds Ratio; Primary Prevention; Risk Factors; Stroke; Vitamin A; Vitamin A Deficiency

The attempts to develop new treatments for acute ischemic stroke have been fraught with costly and spectacularly disappointing failures. Repurposing of safe, older drugs provides a lower risk alternative. Vascular protection is a novel strategy for improving stroke outcome. Promising targets for vascular protection after stroke have been identified, and several of these targets can be approached with "repurposed" old drugs, including statins, angiotensin receptor blockers (ARBs), and minocycline. We tested the vascular protection (ability to reduce hemorrhagic transformation) of three marketed drugs (candesartan, minocycline, and atorvastatin) in the experimental stroke model using three different rat strains [Wistar, spontaneously hypertensive rats (SHR) and type 2 diabetic Goto-Kakizaki (GK) rats]. All agents decreased the infarct size, improved the neurological outcome and decreased bleeding. Mechanisms identified include inhibition of MMP-9, activation of Akt, and increased expression of proangiogenic growth factors. Premorbid vascular damage (presence of either diabetes or hypertension) increased the likelihood of vascular injury after ischemia and reperfusion and improved the response to vascular protection.

Topics: Animals; Anticholesteremic Agents; Antihypertensive Agents; Atorvastatin; Benzimidazoles; Biphenyl Compounds; Brain Infarction; Diabetes Mellitus, Type 2; Disease Models, Animal; Enalapril; Enzyme-Linked Immunosorbent Assay; Functional Laterality; Hemoglobins; Hemorrhage; Heptanoic Acids; Male; Matrix Metalloproteinase 9; Pyrroles; Rats; Rats, Inbred SHR; Rats, Wistar; Reperfusion; Stroke; Tetrazoles; Vascular System Injuries