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Malcolm J West, Paul J Nestel,
Adrienne C Kirby,
Renate Schnabel,
David Sullivan,
R John Simes,
Christine Pollicino,
Edith Lubos,
Thomas F Münzel,
Harvey D White,
Andrew M Tonkin,
Christoph Bickel,
Laurence Tiret,
Stefan Blankenberg
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ABSTRACT: We sought to determine the association between two major biomarkers, the inactive N-terminal fragment of brain natriuretic peptide (NT-proBNP) and tissue inhibitor of metalloproteinase-1 (TIMP-1) and long-term cardiovascular outcomes in a cohort of subjects who had a myocardial infarction or unstable angina 3-36 months previously.
Plasma NT-proBNP and TIMP-1 were measured in a nested case control study of 250 randomly matched subject pairs enrolled in the long-term intervention with pravastatin in ischaemic disease (LIPID) and LIPID extended follow-up studies. Cases (n = 250) were defined as those who had a cardiovascular death, non-fatal myocardial infarction or stroke during the studies. Controls (n = 250) remained event-free for the same follow-up duration (average 2.5 years) as the matched cases. The relationships between cases and plasma NT-proBNP and TIMP-1 were adjusted for the LIPID risk score, treatment allocation and other biomarkers (CRP, IL-6 and white cell count), and examined using a multivariable conditional logistic regression model. NT-proBNP levels were significantly higher in the cases than in the controls [389 (152-864) vs. 198 (93-416) pg/mL, median (25%-75% percentiles), P < 0.001]. The odds ratio (OR) of recurrent cardiovascular events in individuals in the highest quartile was three times higher than those in the lowest quartile (95% confidence interval (CI) 1.8-5.1; P < 0.001). Similarly, TIMP-1 levels were significantly higher among cases compared with controls (806 vs. 736 pg/mL, median: highest vs. lowest quartile: OR 2.8, 95% CI 1.6-4.7; P < 0.001). After adjustment for the LIPID risk score, treatment with pravastatin and other biomarkers, both NT-proBNP and TIMP-1 predicted cardiovascular events significantly and independently of each other.
The study suggests that in subjects with stable ischaemic disease, NT-proBNP and TIMP-1 are independent predictive markers of coronary heart disease outcome.
European Heart Journal 04/2008; 29(7):923-31. · 10.48 Impact Factor
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ABSTRACT: Comparisons of the relation of diet with coronary heart disease (CHD) between countries with similar socioeconomic environments have been few. Patients in Australia and New Zealand (n = 9014) who participated in a large secondary prevention trial had significantly different CHD mortality rates.
The objective of this study was to ascertain the effects of nutrient consumption on cardiovascular disease risk in patients from the 2 countries.
Nutrient consumption patterns were surveyed in a subgroup of 1077 patients on 3 occasions over 4 y during an intervention trial with a statin.
Within the entire cohort of 9014 patients, the New Zealanders had significantly (40%) more cardiovascular deaths than did the Australians. In the subgroup of 1077 patients, the New Zealanders were found at entry to have eaten significantly more total (69.34 +/- 12.35 compared with 66.45 +/- 12.9 g/d) and saturated (26.23 +/- 8.41 compared with 24.37 +/- 7.36 g/d) fat (P < 0.001 for each) and to have significantly (4%) higher concentrations of LDL cholesterol (3.96 +/- 0.74 compared with 3.8 +/- 0.76 mmol/L; P < 0.001) than did the Australians. At baseline, patients with previous coronary artery bypass grafting had diets that were significantly different from those of patients without previous coronary artery bypass grafting. Relations between nutrients and plasma lipids confirmed the direct effects of saturated fatty acids on LDL cholesterol and of alcohol on plasma triacylglycerol and HDL cholesterol. Dietary counseling throughout the trial led to significant improvements in compliance with guidelines. However, neither the baseline nor the improved 1-y nutrient intakes predicted future changes in cardiovascular events.
Differences in CHD mortality and in LDL-cholesterol concentrations between 2 populations with similar socioeconomic and cultural backgrounds were consistent with the amounts and types of fats eaten.
American Journal of Clinical Nutrition 07/2005; 81(6):1322-9. · 6.67 Impact Factor
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ABSTRACT: Elevated serum inflammatory marker levels are associated with a greater long-term risk of cardiovascular events. Because 3-hydroxy-3-methylglutaryl coenzyme-A reductase inhibitors (statins) may have an antiinflammatory action, it has been suggested that patients with elevated inflammatory marker levels may have a greater reduction in cardiovascular risk with statin treatment.
We evaluated the association between the white blood cell count (WBC) and coronary heart disease mortality during a mean follow-up of 6.0 years in the Long-Term Intervention With Pravastatin in Ischemic Disease (LIPID) Study, a clinical trial comparing pravastatin (40 mg/d) with a placebo in 9014 stable patients with previous myocardial infarction or unstable angina. An increase in baseline WBC was associated with greater coronary heart disease mortality in patients randomized to placebo (hazard ratio for 1x10(9)/L increase in WBC, 1.18; 95% CI, 1.12 to 1.25; P<0.001) but not pravastatin (hazard ratio, 1.02; 95% CI, 0.96 to 1.09; P=0.56; P for interaction=0.004). The numbers of coronary heart disease deaths prevented per 1000 patients treated with pravastatin were 0, 9, 30, and 38 for baseline WBC quartiles of <5.9, 6.0 to 6.9, 7.0 to 8.1, and >8.2x10(9)/L, respectively. WBC was a stronger predictor of this treatment benefit than the ratio of total to high-density lipoprotein cholesterol and a global measure of cardiac risk. There was also a greater reduction (P=0.052) in the combined incidence of cardiovascular mortality, nonfatal myocardial infarction, and stroke with pravastatin as baseline WBC increased (by quartile: 3, 41, 61, and 60 events prevented per 1000 patients treated, respectively).
These data support the hypothesis that individuals with evidence of inflammation may obtain a greater benefit from statin therapy.
Circulation 04/2005; 111(14):1756-62. · 14.74 Impact Factor
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ABSTRACT: Homocysteine appears to be causally related to cardiovascular disease and shown to induce endothelial dysfunction. An adverse effect on large elastic arteries has not been reported. In 18 healthy middle-aged subjects, systemic arterial compliance (SAC) was measured over 5h after a standard methionine load. Arterial pressure waves from the carotid artery and aortic flow were measured non-invasively and SAC calculated. Differences in mean SAC values when plasma homocysteine concentrations were raised with a methionine containing meal and on another day when a control meal was eaten were highly significant. SAC fell (arterial stiffness increased) by 22% at 2.5h and by 19% at 5h (treatment x time interaction: P=0.003 and 0.004, respectively). Adjustment for confounders (age, arterial pressure, BMI, LDL cholesterol) did not affect conclusions. Thus, arterial stiffness in the central elastic arterial system increased rapidly at high plasma homocysteine concentrations.
Atherosclerosis 12/2003; 171(1):83-6. · 3.79 Impact Factor
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ABSTRACT: This study was undertaken to address the vascular effects of isolated isoflavones as potential contributors to their cardioprotective properties, focusing on biochanin and formononetin.
In a randomized, double-blind trial, 80 healthy subjects, 46 men and 34 women, 45 to 75 years of age, received isoflavones enriched in either biochanin or formononetin (precursors of genistein and daidzein; 80 mg/d) crossed over randomly with placebo in two 6-week periods. The end points were measured at baseline and after each intervention and included large artery stiffness (systemic arterial compliance and pulse wave velocity), endothelial function in conduit arteries (flow-mediated vasodilation), 24-hour ambulatory blood pressure, and total peripheral resistance. Isoflavone intervention significantly reduced arterial stiffness with improved systemic arterial compliance (P=0.04; repeated-measures ANOVA, Bonferroni correction) attributable to a reduction in total peripheral resistance (P=0.03) and a corresponding reduction in central pulse wave velocity (P=0.02) compared with placebo. Isoflavones did not affect blood pressure (P=0.5) or flow-mediated vasodilation (P=0.44). Improvements seemed limited to formononetin-enriched isoflavones (adjusted P=0.06). Formononetin treatment also reduced circulating vascular adhesion cell molecule-1 (P<0.01).
In normotensive men and postmenopausal women, red clover isoflavones enriched in formononetin reduced arterial stiffness and total vascular resistance but had no effect on blood pressure. These effects may partly explain the lower cardiovascular risk in populations eating isoflavone-rich diets.
Arteriosclerosis Thrombosis and Vascular Biology 06/2003; 23(6):1066-71. · 6.37 Impact Factor
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Paul J Nestel,
Katrine Baghurst,
David M Colquhoun,
R John Simes,
Kirsty Mehalski,
Harvey D White,
Andrew M Tonkin,
Adrienne Kirby,
Christine Pollicino,
Ian Hamilton-Craig,
et al
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Malcolm J West, Paul J Nestel,
Adrienne C. Kirby,
Renate Schnabel,
David Sullivan,
R John Simes,
Christine Pollicino,
Edith Lubos,
Thomas F Munzel,
Harvey D White,
Andrew M Tonkin,
Christoph Bickel,
Laurence Tiret,
Stefan Blankenberg
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Malcolm J West, Paul J Nestel,
Adrienne C. Kirby,
Renate Schnabel,
David Sullivan,
R John Simes,
Christine Pollicino,
Edith Lubos,
Thomas F Munzel,
Harvey D White,
Andrew M Tonkin,
Christoph Bickel,
Laurence Tiret,
Stefan Blankenberg,
Ian Hamilton-Craig,
et al
[show abstract]
[hide abstract]
ABSTRACT: Aims: We sought to determine the association between two major biomarkers, the inactive N-terminal fragment of brain natriuretic peptide (NT-proBNP) and tissue inhibitor of metalloproteinase-1 (TIMP-1) and long-term cardiovascular outcomes in a cohort of subjects who had a myocardial infarction or unstable angina 3–36 months previously. Methods and results: Plasma NT-proBNP and TIMP-1 were measured in a nested case control study of 250 randomly matched subject pairs enrolled in the long-term intervention with pravastatin in ischaemic disease (LIPID) and LIPID extended follow-up studies. Cases (n = 250) were defined as those who had a cardiovascular death, non-fatal myocardial infarction or stroke during the studies. Controls (n = 250) remained event-free for the same follow-up duration (average 2.5 years) as the matched cases. The relationships between cases and plasma NT-proBNP and TIMP-1 were adjusted for the LIPID risk score, treatment allocation and other biomarkers (CRP, IL-6 and white cell count), and examined using a multivariable conditional logistic regression model. NT-proBNP levels were significantly higher in the cases than in the controls [389 (152–864) vs. 198 (93–416) pg/mL, median (25%–75% percentiles), P < 0.001]. The odds ratio (OR) of recurrent cardiovascular events in individuals in the highest quartile was three times higher than those in the lowest quartile (95% confidence interval (CI) 1.8–5.1; P < 0.001). Similarly, TIMP-1 levels were significantly higher among cases compared with controls (806 vs. 736 pg/mL, median: highest vs. lowest quartile: OR 2.8, 95% CI 1.6–4.7; P < 0.001). After adjustment for the LIPID risk score, treatment with pravastatin and other biomarkers, both NT-proBNP and TIMP-1 predicted cardiovascular events significantly and independently of each other. Conclusion: The study suggests that in subjects with stable ischaemic disease, NT-proBNP and TIMP-1 are independent predictive markers of coronary heart disease outcome. Yes Yes
