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M J Landray

Publications and source records attributed to M J Landray.

At least 19 recordsLinked to original sources
PubMed2001

A randomized double-blind placebo-controlled trial of the effect of homocysteine-lowering therapy with folic acid on endothelial function in patients with coronary artery disease.

OBJECTIVES: This study was designed to determine the effects of folic acid therapy on endothelial function in patients with coronary artery disease (CAD). BACKGROUND: Hyperhomocysteinemia, a risk factor for CAD, may cause atherosderosis by oxidative endothelial injury. Folic acid reduces plasma homocysteine, but the effect on adverse vascular events is unknown. METHODS: In a double-blind placebo-controlled trial, 90 patients (mean age [range] 63 [46 to 79] years, 79 men) with CAD were randomized to either folic acid 5 mg or placebo daily for 12 weeks. Endothelial function was assessed by measuring: 1) flow-mediated endothelium-dependent dilation (EDD) of the brachial artery; 2) combined serum nitrite/nitrate (NOx) concentrations and; 3) plasma von Willebrand factor (vWF) concentration. RESULTS: At the end of the study, plasma homocysteine was lower in the folic acid group compared with the placebo group (mean [95% confidence interval] 9.3 (8.5 to 10.1) vs. 12.3 [11.3 to 13.4] micromol/l, p < 0.001). Although there were no significant differences in EDD, serum NOx or plasma vWF between the two groups, there was a greater increase in EDD from baseline in the folic acid group compared to placebo (1.2 [0.7 to 1.8] vs. 0.4 [-0.3 to 1.1]%, p = 0.07). CONCLUSIONS: Folic acid reduced plasma homocysteine and was associated with a trend toward improved endothelial function in patients with CAD. The absence of an unequivocally positive result may have been due to inadequate sample size or chance. This reinforces the need for the results of large randomized controlled trials before the implementation of routine folic acid supplementation.

Aged↗
PubMed2001

Epidemiological evaluation of known and suspected cardiovascular risk factors in chronic renal impairment.

Patients with chronic renal impairment (CRI) are at greatly increased risk for premature vascular disease; however, little is known about its evolution. This paper describes a cohort of patients with CRI and reports study design, baseline demographic and biochemical data, and comparisons with two contemporaneous age- and sex-matched control groups, one with established coronary artery disease and the other without overt vascular disease. Among 369 individuals (median age, 63 years; range, 18 to 88 years; 67% men) with CRI, 34% had a history of vascular disease and 21% had electrocardiographic left ventricular hypertrophy (LVH). Even in those with mild renal impairment (serum creatinine < 2.1 mg/dL), approximately one third had vascular disease and 12% had LVH. A history of hypertension was present in 76% of the CRI group, but as compared with controls, systolic and diastolic blood pressures were not elevated. Low-density lipoprotein (LDL) cholesterol concentration also was not elevated, but CRI was associated with elevated serum triglyceride and plasma homocysteine levels and reduced high-density lipoprotein (HDL) cholesterol, hemoglobin, and serum albumin concentrations. Across the spectrum of CRI, more severe renal dysfunction was associated with lower levels of diastolic blood pressure, LDL and HDL cholesterol, albumin, and hemoglobin, but increased levels of plasma homocysteine. This cross-sectional analysis shows that vascular disease is common in individuals with mild CRI attending a nephrology program and also suggests trends in the levels of a number of potential vascular risk factors with respect to severity of renal dysfunction. These results will be further quantified in a prospective biennial follow-up.

Adolescent↗
PubMed2001

Dyslipidaemia in patients with malignant-phase hypertension.

Low-density lipoprotein (LDL) consists of a heterogeneous group of particles of differing size, density and electrophoretic mobility, smaller particles being more atherogenic. A high proportion of small LDL particles is an independent risk factor for cardiovascular disease. We hypothesized that patients with malignant phase hypertension (MHT), the most severe form of hypertension, would demonstrate a more atherogenic LDL subfraction profile than either non-malignant hypertension (NMHT) or normotensive controls. We compared 16 patients with MHT to 41 patients with untreated NMHT and 45 normotensive controls. LDL subfraction profile was measured by disc polyacrylamide gel electrophoresis using a validated scoring system to calculate the mean size (locus) and heterogeneity (spread) of LDL subfraction mobilities. A higher LDL locus indicates a greater proportion of small LDL subfractions. LDL cholesterol levels were similar in all three groups (p=0.23). High-density lipoprotein cholesterol (HDL-C) levels were significantly lower (p<0.001) and serum triglyceride concentrations significantly higher (p=0.02) in the MHT group, compared to normotensive controls. LDL locus was greater in the NMHT group than in the normotensive controls and intermediate in the MHT group (p=0.008). There was no significant difference in LDL spread (p=0.26). Serum triglyceride concentrations were not significantly higher after adjusting for confounding variables. MHT is associated with an abnormal lipid profile, characterized by low HDL-cholesterol concentration. This dyslipidaemia may be partly responsible for the vascular complications and the poor prognosis of these patients.

Analysis of Variance↗
PubMed2000

Does folic acid decrease plasma homocysteine and improve endothelial function in patients with predialysis renal failure?

BACKGROUND: Considerable evidence suggests that hyperhomocysteinemia is an independent vascular risk factor that promotes atherosclerosis by inducing endothelial dysfunction. Although folic acid reduces hyperhomocysteinemia, the effect on adverse vascular events is unknown. We hypothesized that in patients with chronic renal failure, a condition associated with both hyperhomocysteinemia and atherosclerosis, treatment with folic acid would improve endothelial function. METHODS AND RESULTS: In a prospective, double-blind protocol, 100 patients (mean age 62 years, 67 men) with predialysis chronic renal failure were randomized to 5 mg folic acid or placebo daily for 12 weeks. Endothelial function was assessed by measuring (1) endothelium-dependent dilation of the brachial artery, (2) combined serum nitrite/nitrate concentrations, and (3) plasma von Willebrand factor concentration. Baseline characteristics of the 2 groups were similar. At the end of the study, both serum and red cell folate concentrations were greater in the folic acid group than the placebo group [mean (95% CI) 39.0 (29.8 to 51.0) versus 7.7 (6.6 to 8.9) microg/L and 739 (613 to 891) versus 220 (184 to 262) microg/L, respectively; both P<0.001]. Despite a reduction in hyperhomocysteinemia in the folic acid group compared with the placebo group [15.1 (14.1 to 16.2) versus 20.1 (18.2 to 22.2) micromol/L; P<0.001], there were no significant differences in endothelium-dependent dilation, combined serum nitrite/nitrate concentrations, or plasma von Willebrand factor concentration between the 2 groups. CONCLUSIONS: High-dose folic acid lowers but fails to normalize hyperhomocysteinemia in patients with predialysis chronic renal failure. This was not accompanied by an improvement of endothelial function and suggests that treatment with folic acid may not reduce the burden of vascular disease in uremia.

Aged↗
PubMed2000

Sudden death: ACE inhibitors and beta-blockers.

Sudden death is extremely common in patients suffering from cardiovascular diseases. At least one third of those with hypertension and probably about half of those who survive a myocardial infarction or suffer from cardiac failure who die in a clinical trial, die suddenly. Beta-blockers reduce the risk of sudden death in patients with cardiovascular disease, particularly in those who have had a myocardial infarction or heart failure. ACE inhibitors are perhaps less effective. Other cardiovascular drugs have not been shown to reduce the risk of sudden death.

Adrenergic beta-Antagonists↗
PubMed2000

A pilot study of streptokinase-induced endothelial injury and platelet activation following acute myocardial infarction.

OBJECTIVE: To relate the changes in serum vitamin E, an essential antioxidant, to changes in fibrinogen, as well as indices of endothelial damage [as indicated by plasma markers, soluble thrombomodulin (sTM) and von Willebrand factor (vWf), and an index of platelet activation (soluble P selectin (sPsel)], in myocardial infarction treated with thrombolytic therapy. DESIGN AND SETTING: Prospective longitudinal pilot study in a teaching hospital Coronary Care Unit. SUBJECTS AND INTERVENTION: Seventeen patients (12 men: mean age (62 years +/- SD 11 years) admitted with acute myocardial infarction (AMI), who were given thrombolytic therapy, and 59 healthy controls. RESULTS: Baseline levels of fibrinogen (Mann-Whitney test, P = 0.0055) and vWf (P < 0.001) were significantly higher than controls, but sPsel, sTM or vitamin E levels were not significantly different. Following thrombolysis, as expected, median concentrations of plasma fibrinogen fell profoundly (Friedman ANOVA P < 0.001) so that after 45 min, levels were undetectable in 13 patients. At 24-h median fibrinogen concentration had recovered to approximately 30% of baseline (P < 0.01) and was still undetectable in three patients. Levels of vWf and sPsel increased steadily, reaching significance after three hours (both P < 0.05). However, levels of sTM rose immediately after thrombolysis, peaking between 1 and 3 h, and remained elevated at 24 h. These increases corresponded to a simultaneous early fall in serum vitamin E concentrations. CONCLUSION: The present pilot study demonstrates significant endothelial damage and platelet activation in association with increased oxidative stress following streptokinase therapy for AMI.

Aged↗
PubMed2000

Abnormalities of endothelial function in patients with predialysis renal failure.

BACKGROUND: Endothelial dysfunction plays an important role in the development of atherosclerotic vascular disease, which is the leading cause of mortality in patients with chronic renal failure. OBJECTIVE: To examine the relation between predialysis renal failure and endothelial function. DESIGN: Two groups were studied: 80 patients with non-diabetic chronic renal failure and 26 healthy controls, with similar age and sex distributions. Two indices of endothelial function were assessed: high resolution ultrasonography to measure flow mediated endothelium dependent dilatation of the brachial artery following reactive hyperaemia, and plasma concentration of von Willebrand factor. Endothelium independent dilatation was also assessed following sublingual glyceryl trinitrate. The patients were divided into those with and without overt atherosclerotic vascular disease. RESULTS: Although patients with chronic renal failure had significantly impaired endothelium dependent dilatation compared with controls (median (interquartile range), 2.6% (0.7% to 4.8%) v 6.5% (4.8% to 8.3%); p < 0.001) and increased von Willebrand factor (254 (207 to 294) v 106 (87 to 138) iu/dl; p < 0.001), there was no difference between renal failure patients with and without atherosclerotic vascular disease. Within the chronic renal failure group, endothelium dependent dilatation and von Willebrand factor were similar in patients in the upper and lower quartiles of glomerular filtration rate (2.7% (0.7% to 6.7%) v 2.8% (1.1% to 5.0%); and 255 (205 to 291) v 254 (209 to 292) iu/dl, respectively). Endothelium independent dilatation did not differ between the renal failure or control groups and was also similar in patients with renal failure irrespective of the degree of renal failure or the presence of atherosclerotic vascular disease. CONCLUSIONS: Endothelial function is abnormal in chronic renal failure, even in patients with mild renal insufficiency and those without atherosclerotic vascular disease, suggesting that uraemia may directly promote the development of atherosclerosis early in the progression of chronic renal failure.

Arteriosclerosis↗
PubMed1999

White coat hypertension and carotid atherosclerosis.

To investigate further the relationship between atherosclerotic vascular disease and blood pressure, and the phenomenon of white coat hypertension, we performed a cross-sectional study of patients referred for carotid Doppler scanning, to determine the relationship between ambulatory blood pressure monitoring (ABPM) and carotid atherosclerosis. We studied 79 patients (51 men, 28 women) undergoing Doppler ultrasound examination of the carotid arteries: 44 (56%) had evidence of carotid atherosclerosis on Doppler ultrasound examination ("disease group"), whilst 35 (44%) had normal carotid arteries ("controls"). "Adequate" ABPM recordings, defined by > 90% of recordings over the 24 h, were available in 51 patients (30 positive, 21 negative). There were no significant differences in mean daytime, mean night-time or mean 24 h ABPM recordings between those with and without carotid atherosclerosis. Mean manual clinic systolic blood pressure was significantly greater in those with carotid atherosclerosis than in controls (146.7 +/- 25.2 vs 131.1 +/- 35 mmHg, p < 0.005). In patients with carotid atherosclerosis, the first systolic blood pressure ABPM recording was not significantly different from the mean manual clinic recording (mean difference -1.5 mmHg, 95% confidence interval (CI) -7.9 to 4.8 mmHg). The initial diastolic blood pressure ABPM recording was significantly higher than the mean manual recording. Carotid atherosclerosis was identified in 53% of normotensive controls compared with 56% of white coat hypertensives and 75% of persistent hypertensives. One-third (9/27) of the patients with normal carotid arteries did not have nocturnal dipping ("non-dippers") compared with 50% (12/24) of the atherosclerotic patients. This study suggests that carotid atherosclerosis may be associated with white coat hypertension. Our study adds to the body of evidence that white coat hypertension is associated with end-organ damage and is not simply a benign disease. Such patients should be screened for other cardiovascular risk factors and should be monitored for the development of persistent hypertension.

Aged↗
PubMed1998

Association of atherogenic low-density lipoprotein subfractions with carotid atherosclerosis.

Patients with carotid atherosclerosis are at increased risk of both stroke and ischaemic heart disease. Low-density lipoprotein (LDL) is a heterogeneous group of particles, with small, dense particles being more atherogenic. We studied 79 patients (51 men, mean +/- SD age 62.4 +/- 11.7 years) referred for Doppler ultrasound assessment of the carotid arteries. Evidence of carotid atherosclerosis, defined as the presence of atherosclerotic plaque, stenosis or occlusion in one or more of the six carotid artery segments examined, was found in 44 patients (56%). LDL subfractions were analysed by disc polyacrylamide gel electrophoresis with prior ultracentrifugation of serum to remove chylomicrons. This method produces a LDL score; the higher the score, the greater the proportion of the more atherogenic LDL subfractions. Mean LDL score was significantly higher in diseased patients (mean +/- SD, 1.56 +/- 0.61) than the normal group (1.26 +/- 0.65) (t = 2.12, p = 0.037). There was no significant association between LDL score and severity of carotid artery stenosis. Age (adjusted odds ratio 1.09, 95% CI 1.03-1.15) and smoking history (2.09, 95% CI 1.10-3.98) predicted carotid atherosclerosis in logistic regression analysis, with LDL score achieving borderline significance (2.20, 95% CI 0.91-5.29). Small, dense LDL subfractions are associated with carotid atherosclerosis and may be a modifiable risk factor for stroke as well as ischaemic heart disease.

Age Factors↗
PubMed1998

Pyrexia, anaemia and acute renal failure secondary to omeprazole.

We present the case of a 77-year-old woman who initially presented with pyrexia of unknown origin, anaemia and mild renal impairment. When her omeprazole was stopped she improved rapidly. When omeprazole was re-started she developed fever and acute renal failure, which again settled quickly on discontinuation of omeprazole. This case demonstrates how drugs can cause severe multisystem disorders that may appear to be infective or inflammatory.

Acute Kidney Injury↗