Biomedical subjects

Ann Rumley

Publications and source records attributed to Ann Rumley.

At least 19 recordsLinked to original sources

PubMed2007

Inflammatory, haemostatic, and rheological markers for incident peripheral arterial disease: Edinburgh Artery Study.

AIMS: Recently, markers of inflammation, haemostasis, and blood rheology have received much attention as risk factors for coronary heart disease and stroke. However, their role in peripheral arterial disease (PAD) is not well established and some of them, including the pro-inflammatory cytokine interleukin-6 (IL-6), have not been examined before in prospective epidemiological studies. METHODS AND RESULTS: In the Edinburgh Artery Study, we studied the development of PAD in the general population and evaluated 17 potential blood markers as predictors of incident PAD. At baseline (1987), 1519 men and women free of PAD aged 55-74 were recruited. After 17 years, 208 subjects had developed symptomatic PAD. In analysis adjusted for cardiovascular risk factors and baseline cardiovascular disease (CVD), only C-reactive protein, fibrinogen, lipoprotein (a), and haematocrit [hazard ratio (95% CI) corresponding to an increase equal to the inter-tertile range 1.30 (1.08, 1.56), 1.16 (1.05, 1.17), 1.22 (1.04, 1.44), 1.22 (1.08, 1.38)] were significantly (P < 0.01) associated with PAD. However, these markers provided very little prognostic information for incident PAD to that obtained by cardiovascular risk factors and the ankle brachial index. Other markers including IL-6, intracellular adhesion molecule 1, d-dimer, tissue plasminogen activator antigen, and plasma and blood viscosities showed weak associations, which were considerably attenuated when CVD risk factors were accounted for. CONCLUSIONS: Our prospective data showed that several inflammatory, haemostatic, and rheological markers are associated with incident PAD; however, their clinical utility is likely to be limited. Future research is necessary to validate the importance of these biomarkers explicitly on PAD and to address the causality of the reported associations.

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PubMed2006

Renal function and cardiovascular mortality in elderly men: the role of inflammatory, procoagulant, and endothelial biomarkers.

AIMS: To assess the extent to which inflammatory, procoagulant, and endothelial biomarkers modify the relationship between diminished renal function and cardiovascular mortality. METHODS AND RESULTS: Prospective study of 4029 men aged 60-79 years followed up for a mean period of 6 years, during which 304 cardiovascular deaths occurred. Predicted estimated glomerular filtration rate (eGFR) was used as a measure of renal function. Reduced eGFR was associated with increased prevalence of established cardiovascular risk factors [cardiovascular disease, diabetes, hypertension, left ventricular (LV) hypertrophy, and dyslipidaemia] and higher levels of inflammatory markers [interleukin 6 (IL-6), C-reactive protein], endothelial markers [von Willebrand factor (vWF) and tissue plasminogen activator], activated coagulation markers (fibrin D-dimer), and blood viscosity. Cardiovascular mortality risk increased with decreasing levels of eGFR, particularly among men with eGFR <60 mL/min per 1.73 m(2) even after adjustment for established risk factors (adjusted RR 1.49, 95% CI 1.10, 2.03; <60 vs. > or =70 mL/min per 1.73 m(2)). The association was attenuated after further adjustment for vWF, D-dimer, and IL-6 (adjusted RR 1.34, 95% CI 0.98-1.82). CONCLUSION: Mild-to-moderate renal insufficiency is associated with significantly increased cardiovascular mortality in elderly men, which is partly explained by the increased prevalence of established risk factors, markers of coagulation, endothelium, and inflammation.

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PubMed2006

Association between plasma IL-6, the IL6 -174G>C gene variant and the metabolic syndrome in type 2 diabetes mellitus.

Elevated plasma interleukin-6 (IL-6) is associated with coronary heart disease (CHD), impaired glucose tolerance (IGT), and type 2 diabetes (T2DM). We and others have described an association between the human interleukin-6 -174G>C gene variant and body mass index (BMI). Within our previous sample of subjects with T2DM, we measured plasma IL-6 and grouped subjects by the WHO-defined metabolic syndrome, in order to study the association between the -174G>C gene variant, plasma IL-6 and the metabolic syndrome (and component parts). Genotype was obtained in 571 Caucasian subjects with plasma IL-6 measures. There was a significant association between genotype and plasma IL-6 (GG vs GC vs CC: 3.23+/-0.93 pg/ml vs 3.42+/-0.95 pg/ml vs 4.16+/-1.18 pg/ml, p=0.02; for GG/GC vs CC p=0.008). No interactions were observed between genotype and the individual components of the metabolic syndrome in determining plasma IL-6. Increased plasma IL-6 was also associated with the number of components (none vs 1 vs 2 vs > or =3: 2.67+/-0.71 pg/ml vs 2.97+/-0.94 pg/ml vs 4.07+/-1.13 pg/ml, p<0.0001). Within the sample, 76% of CC compared to 56% of GG subjects had the metabolic syndrome (p=0.007). Further analysis of association between the genotype and the components of the metabolic syndrome revealed no further associations than that with BMI previously described. The association of this gene variant with the metabolic syndrome is intimately linked with obesity per se. Further prospective work is required to explore the effect of this gene variant in relation to obesity, the metabolic syndrome and 'prediabetes'.

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PubMed2006

Plasma leptin: associations with metabolic, inflammatory and haemostatic risk factors for cardiovascular disease.

BACKGROUND AND AIM: Leptin, an adipocyte-derived protein, regulating food intake and metabolism has been implicated in the development of coronary heart disease. We have examined the relationship between leptin and vascular risk factors including insulin resistance, metabolic, inflammatory and haemostatic risk factors. METHODS AND RESULTS: The study was carried out in 3640 non-diabetic men aged 60-79 years drawn from general practices in 24 British towns and who were not on warfarin. Leptin was strongly positively correlated with waist circumference (r=0.58; p<0.0001). Leptin concentrations decreased significantly with increasing physical activity and were lowered in cigarette smokers and elevated in men with pre-existing coronary heart disease and stroke; alcohol intake showed no association with leptin concentration. After adjustment for waist circumference and these lifestyle factors, increased leptin was independently associated with significant increases in insulin resistance, triglycerides, inflammatory markers (interleukin-6, C-reactive protein, fibrinogen, plasma viscosity), coagulation factor VIII, endothelial markers von Willebrand factor, tissue plasminogen activator, and fibrin D-dimer levels; and a decrease in HDL-cholesterol. No association was seen between leptin and blood pressure, total cholesterol, glucose or white cell count after adjusting for waist circumference. Further adjustment for insulin resistance abolished the relationships between leptin and triglycerides and HDL-cholesterol, weakened the associations with the haemostatic factors although they remained significant, but made minor differences to the associations with inflammatory markers. CONCLUSION: Plasma leptin is associated with insulin resistance, inflammation and disturbances in haemostasis independent of waist circumference, suggesting possible pathways by which leptin may influence risk of cardiovascular disease.

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PubMed2006

D-dimer predicts early clinical progression in ischemic stroke: confirmation using routine clinical assays.

BACKGROUND AND PURPOSE: Plasma d-dimer levels, measured using a research laboratory assay, independently predict progressing ischemic stroke. We wished to confirm these findings using commercially available assays and to provide data to allow the design of intervention studies. METHODS: We studied 219 consecutive acute ischemic stroke admissions of whom 54 (25%) met criteria for progressing stroke. RESULTS: There were strong correlations between d-dimer results as measured by the Biopool AB, MDA and VIDAS assays; correlation coefficients r=0.91 to 0.94; all P<0.001. In binary logistic regression analyses, d-dimer, as measured by the 3 different assays, was an independent predictor of progressing stroke (odds ratios, 1.87 to 2.45; all P<0.001). This confirms the results of our original analysis (Biopool AB) using 2 commercial d-dimer assays, demonstrating the potential usefulness of d-dimer in providing early prognostic information after ischemic stroke in different clinical settings. We also provide information on the performance of the 3 assays in predicting progressing stroke at a variety of cutoff values. CONCLUSIONS: Ischemic stroke patients at high risk of early progression can be identified using commercial d-dimer measurements. This could allow selection of high-risk patients for inclusion in randomized trials of early antithrombotic treatments.

Brain Ischemia↗

PubMed2006

Reduced lung function in patients with abdominal aortic aneurysm is associated with activation of inflammation and hemostasis, not smoking or cardiovascular disease.

OBJECTIVE: Abdominal aortic aneurysms often coexist with reduced lung function and chronic obstructive pulmonary disease (COPD). These conditions are each associated with cigarette smoking, cardiovascular disease, and evidence of increased inflammatory and hemostatic activity. The aim of this study was to determine if these factors accounted for the link between aneurysms and pulmonary disease. METHODS: The design was a case-control study comparing patients with an asymptomatic abdominal aortic aneurysm with population-based controls without an aneurysm. Aneurysms were diagnosed by ultrasound scan, and pulmonary function was measured by respiratory questionnaire and spirometry. Activation of inflammation and hemostasis was measured by assay of plasma interleukin-6 (IL-6), fibrinogen, von Willebrand factor (vWF), tissue plasminogen activator (tPA) antigen, fibrin D-dimer, and plasmin antiplasmin complexes. RESULTS: Cases with an abdominal aortic aneurysm (n = 89) had more COPD and worse expiratory lung function as measured by forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) than controls (n = 98) (FEV1, 1.9 vs 2.2 L, P < .01; FEV1/FVC, 0.67 vs 0.75, P < .001) and did not differ in restrictive function (FVC, 2.9 vs 3.0 L, P = .33). Cases also had higher levels of lifetime cigarette smoking (30 vs 24 pack-years, P < 0.01), cardiovascular disease (35% vs 18%, P = .01), plasma fibrinogen (3.5 vs 3.1 g/L, P = .02), IL-6 (2.8 vs 1.8, pg/mL, P < .001), plasmin antiplasmin complexes (596 vs 384 microg/L, P = .01), and D-dimer (442 vs 93 ng/mL, P < .001). On multiple logistic regression analysis of lung function and COPD on the risk of aneurysm, both cigarette smoking and cardiovascular disease had little effect on the relationships. For the markers of activated inflammation and hemostasis, plasmin antiplasmin complexes and D-dimer had the most important confounding effect on the odds ratios. All markers combined had a substantial effect: odds ratio of aneurysm for a one standard deviation decrease in FEV1 fell from 2.3 (95% confidence interval [CI], 1.5 to 3.5) (P < .01) to 1.3 (95% CI, 0.55 to 2.4) (P > or = .05). CONCLUSION: The association between reduced respiratory function and abdominal aortic aneurysm was not accounted for by cigarette smoking or cardiovascular disease. We hypothesize that activation of inflammation and hemostasis in response to injury may be an important explanation of the association between aneurysm formation and reduced respiratory function. Further studies are required to test this hypothesis.

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PubMed2006

Associations of vitamin C status, fruit and vegetable intakes, and markers of inflammation and hemostasis.

BACKGROUND: It has been suggested that a high dietary intake and high circulating concentrations of vitamin C may protect against ischemic heart disease. OBJECTIVES: The objective was to examine the associations between dietary and plasma vitamin C concentrations, fruit and vegetable intakes, and markers of inflammation and hemostasis associated with cardiovascular disease in older men free of cardiovascular disease. DESIGN: This cross-sectional study examined 3258 men aged 60-79 y with no physician diagnosis of myocardial infarction, stroke, or diabetes and who were drawn from general practices in 24 British towns. Fruit and vegetable intakes and dietary vitamin C were assessed by using a food-frequency questionnaire. RESULTS: Plasma vitamin C, fruit intake, and dietary vitamin C intake were significantly and inversely associated with mean concentrations of C-reactive protein, an acute phase reactant, and tissue plasminogen activator (t-PA) antigen, a marker of endothelial dysfunction, even after adjustment for confounders. Vegetable intake was correlated significantly (inversely) only with t-PA. For plasma vitamin C (highest versus lowest quartile), the adjusted odds of elevated C-reactive protein and t-PA (highest tertile versus lowest tertile) were 0.56 (95% CI: 0.44, 0.71) and 0.79 (0.62, 1.00); for fruit intake, the corresponding odds ratios were 0.76 (0.60, 0.95) and 0.76 (0.61, 0.95). Plasma (but not dietary) vitamin C also showed inverse associations with both fibrinogen concentrations and blood viscosity. No associations were seen with von Willebrand factor or factor VIII. CONCLUSION: The findings suggest that vitamin C has antiinflammatory effects and is associated with lower endothelial dysfunction in men with no history of cardiovascular disease or diabetes.

Acute-Phase Proteins↗

PubMed2006

The association between homocysteine and myocardial infarction is independent of age, sex, blood pressure, cholesterol, smoking and markers of inflammation: the Glasgow Myocardial Infarction Study.

UNLABELLED: Homocysteine is associated with both myocardial infarction and arterial wall inflammation. To establish whether homocysteine is associated with myocardial infarction after adjusting for age, sex, the major cardiovascular risk factors and inflammatory risk predictors (fibrinogen, C-reactive protein and interleukin-6). A case-control study, using 364 myocardial infarction cases drawn from the north Glasgow MONICA study, 3-9 months after their event, and 383 controls drawn from the general population of the same geographical area. The odds ratio for myocardial infarction increased progressively across the four quarters of the homocysteine distribution, after adjusting for only age and sex or for the full adjustment (age, sex, smoking, systolic blood pressure, total cholesterol, fibrinogen, C-reactive protein and interleukin-6). The odds ratios produced by the two adjustments were similar. Comparing the top quarter with the bottom quarter of homocysteine, the odds ratio was 2.21 (95% confidence interval: 1.30-3.76) after the full adjustment. The odds ratio for a 5 micromol/l increase in homocysteine was 1.12 (95% confidence interval: 1.01-1.24) after the full adjustment. CONCLUSION: This study suggests that homocysteine has an effect on cardiovascular risk over and above that of inflammatory markers and the major cardiovascular risk factors.

Age Factors↗

PubMed2006

Our inability to predict thromboembolic events after prosthetic valve surgery.

BACKGROUND AND AIM OF THE STUDY: Thromboembolic and bleeding complications detract from outcome for patients with prosthetic heart valves. The study aim was to investigate whether measurement of coagulation activation markers and transcranial Doppler ultrasound microembolic signals (MES) could identify patients at subsequent higher risk of thromboembolism or bleeding events. METHODS: A total of 526 patients (mean age 66 years; 266 males, 260 females) who underwent elective valve replacement surgery was enrolled between April 1999 and October 2002. Clinical assessment and blood sampling for coagulation activation markers was performed preoperatively and at three and 12 months postoperatively. Transcranial Doppler MES were recorded in the first 144 patients. Status was reviewed between 21st April and 9th June 2005, with 99.4% follow up. RESULTS: Among patients, 62% had an aortic valve replaced, and mechanical valves constituted 60% of all implants. The mean follow up was 3.61 years; total follow up was 1,899.2 patient-years (pt-yr). In total, 115 patients died, while 61 experienced a total of 80 thromboembolic events: linearized event rates were 3.94% (mechanical valves) and 4.4% (bioprostheses). There was no difference between mitral and aortic implants, or among bileaflet, tilting-disc mechanical and porcine valves. Atrial fibrillation was not influential. Coagulation activation markers were not associated with thromboembolic events, except for an elevated von Willebrand factor (vWF), which was associated with a five-fold increase in embolic event rate. Fifty-one patients experienced 59 bleeding events; eight patients experienced multiple events. Linearized event rates were 3.37% (mechanical valves) and 2.49% (bioprostheses). The INR was suboptimal in 44-58% of patients. Transcranial Doppler MES were not associated with blood coagulation markers or thromboembolic events. CONCLUSION: Coagulation activation markers (except vWF) and MES did not predict thromboembolic events in valve replacement patients. Thromboembolic and bleeding event rates for West of Scotland patients generally exceeded reported rates: suboptimal anticoagulation appeared common and most likely influenced thromboembolic and bleeding event rates more than any other factor.

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PubMed2005

Hemostatic factors, inflammatory markers, and progressive peripheral atherosclerosis: the Edinburgh Artery Study.

The interplay between inflammatory and hemostatic mechanisms may play a crucial role in the development and progression of atherosclerosis. The authors evaluated the separate and joint associations of hemostatic and inflammatory variables on peripheral atherosclerotic progression in the Edinburgh Artery Study, a population cohort study of 1,592 men and women aged 55-74 years that started in 1987. Levels of fibrinogen, fibrin D-dimer, von Willebrand factor, tissue plasminogen activator antigen, factor VII, prothrombin fragment 1 + 2, urinary fibrinopeptide A, C-reactive protein, and interleukin-6 were measured at baseline. Arm and ankle blood pressures were measured, and atherosclerotic progression was assessed by computing ankle brachial index (ABI) at baseline (1,582 participants) and after 12 years of follow-up (813 participants). Fibrinogen (p = 0.05) and D-dimer (p < or = 0.05) were significantly associated with ABI change independently of baseline ABI and cardiovascular disease risk factors. However, these associations were no longer significant when analyses were adjusted for either C-reactive protein or interleukin-6. Moreover, subjects with higher levels of both D-dimer and interleukin-6 at baseline had the greatest ABI decline. In conclusion, fibrinogen and D-dimer, but not other hemostatic factors, were associated with progressive peripheral atherosclerosis. Since D-dimer and fibrinogen are acute phase reactants, these data support the hypothesis that inflammation is more related to atherosclerosis than is hypercoagulation.

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PubMed2005

C-reactive protein and its role in metabolic syndrome: mendelian randomisation study.

BACKGROUND: Circulating C-reactive protein (CRP) is associated with the metabolic syndrome and might be causally linked to it. Our aim was to generate estimates of the association between plasma CRP and metabolic syndrome phenotypes that were free from confounding and reverse causation, to assess the causal role of this protein. METHODS: We examined associations between serum CRP concentration and metabolic syndrome phenotypes in the British Women's Heart and Health Study. We then compared these estimates with those derived from a mendelian randomised framework with common CRP gene haplotypes to generate unconfounded and unbiased estimates of any causal associations. FINDINGS: In a sample of British women, body-mass index (BMI), systolic blood pressure, waist-to-hip ratio, serum concentrations of HDL cholesterol and triglycerides, and insulin resistance were all associated with plasma CRP concentration. CRP haplotypes were associated with plasma CRP concentration (p<0.0001). With instrumental variable analyses, there was no association between plasma CRP concentration and any of the metabolic syndrome phenotypes analysed. There was strong evidence that linear regression and mendelian randomisation based estimation gave conflicting results for the CRP-BMI association (p=0.0002), and some evidence of conflicting results for the association of CRP with the score for insulin resistance (p=0.0139), triglycerides (p=0.0313), and HDL cholesterol (p=0.0688). INTERPRETATION: Disparity between estimates of the association between plasma CRP and phenotypes comprising the metabolic syndrome derived from conventional analyses and those from a mendelian randomisation approach suggests that there is no causal association between CRP and the metabolic syndrome phenotypes.

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PubMed2005

Which hemostatic markers add to the predictive value of conventional risk factors for coronary heart disease and ischemic stroke? The Caerphilly Study.

BACKGROUND: Few studies have examined whether hemostatic markers contribute to risk of coronary disease and ischemic stroke independently of conventional risk factors. This study examines 11 hemostatic markers that reflect different aspects of the coagulation process to determine which have prognostic value after accounting for conventional risk factors. METHODS AND RESULTS: A total of 2398 men aged 49 to 65 years were examined in 1984 to 1988, and the majority gave a fasting blood sample for assay of lipids and hemostatic markers. Men were followed up for a median of 13 years, and cardiovascular disease (CVD) events were recorded. There were 486 CVD events in total, 353 with prospective coronary disease and 133 with prospective ischemic stroke. On univariable analysis, fibrinogen, low activated protein C ratio, D-dimer, tissue plasminogen activator (tPA), and plasminogen activator inhibitor-1 (PAI-1) were associated significantly with risk of CVD. On multivariable analyses with conventional risk factors forced into the proportional hazards model, fibrinogen, D-dimer, and PAI-1 were significantly associated with risk of CVD, whereas factor VIIc showed an inverse association (P=0.001). In a model that contained the conventional risk factors, the hazard ratio for subsequent CVD in the top third of the distribution of predicted risk relative to the bottom third was 2.7 for subjects without preexisting CVD. This ratio increased to 3.7 for the model that also contained the 4 hemostatic factors. CONCLUSIONS: Fibrinogen, D-dimer, PAI-1 activity, and factor VIIc each has potential to increase the prediction of coronary disease/ischemic stroke in middle-aged men, in addition to conventional risk factors.

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PubMed2005

Associations of inflammatory and hemostatic variables with the risk of recurrent stroke.

BACKGROUND AND PURPOSE: Several prospective studies have shown significant associations between plasma fibrinogen, viscosity, C-reactive protein (CRP), fibrin D-dimer, or tissue plasminogen activator (tPA) antigen and the risk of primary cardiovascular events. Little has been published on the associations of these variables with recurrent stroke. We studied such associations in a nested case-control study derived from the Perindopril Protection Against Recurrent Stroke Study (PROGRESS). METHODS: Nested case-control study of ischemic (n=472) and hemorrhagic (n=83) strokes occurring during a randomized, placebo-controlled multicenter trial of perindopril-based therapy in 6105 patients with a history of stroke or transient ischemic attack. Controls were matched for age, treatment group, sex, region, and most recent qualifying event at entry to the parent trial. RESULTS: Fibrinogen and CRP were associated with an increased risk of recurrent ischemic stroke after accounting for the matching variables and adjusting for systolic blood pressure, smoking, peripheral vascular disease, and statin and antiplatelet therapy. The odds ratio for the last compared with the first third of fibrinogen was 1.34 (95% CI, 1.01 to 1.78) and for CRP was 1.39 (95% CI, 1.05 to 1.85). After additional adjustment for each other, these 2 odds ratios stayed virtually unchanged. Plasma viscosity, tPA, and d-dimer showed no relationship with recurrent ischemic stroke, although tPA was significant for lacunar and large artery subtypes. Although each of these variables showed a negative relationship with recurrent hemorrhagic stroke, none of these relationships achieved statistical significance. CONCLUSIONS: Fibrinogen and CRP are risk predictors for ischemic but not hemorrhagic stroke, independent of potential confounders.

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PubMed2005

C-reactive protein, interleukin-6, and soluble adhesion molecules as predictors of progressive peripheral atherosclerosis in the general population: Edinburgh Artery Study.

BACKGROUND: The relationship between levels of circulating inflammatory markers and risk of progressive atherosclerosis is relatively undetermined. We therefore studied inflammatory markers as predictors of peripheral atherosclerotic progression, measured by the ankle-brachial index (ABI) at 3 consecutive time points over 12 years. METHODS AND RESULTS: The Edinburgh Artery Study is a population cohort study of 1592 men and women aged 55 to 74 years. C-reactive protein (CRP), interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), and E-selectin were measured at baseline. Valid ABI measurements were obtained on 1582, 1081, and 813 participants at baseline and 5-year and 12-year follow-up examinations, respectively. At baseline, a significant trend was found between higher plasma levels of CRP (P< or =0.05) and increasing severity of peripheral arterial disease (PAD), after adjustment for baseline cardiovascular risk factors. IL-6 at baseline (P< or =0.001) was associated with progressive atherosclerosis at 5 years (ABI change from baseline), and CRP (P< or =0.01), IL-6 (P< or =0.001), and ICAM-1 (P< or =0.01) were associated with changes at 12 years, independently of baseline ABI, cardiovascular risk factors, and baseline cardiovascular disease. Only IL-6 independently predicted ABI change at 5 years (P< or =0.01) and 12 years (P< or =0.05) in analyses of all inflammatory markers simultaneously and adjusted for baseline ABI, cardiovascular risk factors, and cardiovascular disease at baseline. CONCLUSIONS: These findings suggest that CRP, IL-6, and ICAM-1 are molecular markers associated with atherosclerosis and its progression. IL-6 showed more consistent results and stronger independent predictive value than other inflammatory markers.

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PubMed2005

Associations between cigarette smoking, pipe/cigar smoking, and smoking cessation, and haemostatic and inflammatory markers for cardiovascular disease.

AIMS: To examine the associations between cigarette smoking, pipe/cigar smoking, and years since quitting smoking, and inflammatory and haemostatic markers. METHODS AND RESULTS: A study in 2920 men aged 60-79 with no history of myocardial infarction, angina, stroke, or diabetes, and who were not on warfarin, from general practices in 24 British towns. After adjustment for other major cardiovascular risk factors, compared with never smokers, current cigarette smokers showed significantly higher levels of C-reactive protein (2.53 vs. 1.35 mg/L), white cell count (7.92 vs. 6.42 x 10(9)/L), and fibrinogen (3.51 vs. 3.13 g/L). They also showed higher levels of haematocrit, blood and plasma viscosity, tissue plasminogen activator antigen, and fibrin D-dimer, and lower levels of albumin. Primary pipe/cigar smokers showed levels similar to never smokers. Ex-cigarette smokers and secondary pipe/cigar smokers showed intermediate levels although secondary pipe/cigar smokers showed higher odds of having elevated white cell count and fibrinogen than ex-cigarette smokers. Most inflammatory and haemostatic levels improved within 5 years of smoking cessation but took over 20 years to revert to levels of never smokers. CONCLUSION: These findings suggest that activation of inflammation and haemostasis may be potential mechanisms by which cigarette and pipe/cigar smoking increase cardiovascular risk.

Adult↗

PubMed2005

Association of C-reactive protein with blood pressure and hypertension: life course confounding and mendelian randomization tests of causality.

BACKGROUND: C-reactive protein (CRP) has repeatedly been associated with blood pressure and prevalent and incident hypertension, but whether a causal link exists is uncertain. METHODS AND RESULTS: We assessed the cross-sectional relations of CRP to systolic blood pressure, pulse pressure, and prevalent hypertension in a representative sample of >3500 British women aged 60 to 79 years. For both outcomes, substantial associations were observed. However, these associations were greatly attenuated by adjustment for a wide range of confounding factors acting over the life course. We further investigated causality using a Mendelian randomization approach by examining the association of the 1059G/C polymorphism in the human CRP gene with CRP and with blood pressure, pulse pressure, and hypertension. The polymorphism was associated with a robust difference in CRP, and the expectation would be for higher blood pressure and pulse pressure and greater prevalence of hypertension among those carrying the genetic variant associated with higher CRP levels. This was not observed, and the predicted causal effects of CRP on blood pressure, pulse pressure, and hypertension using instrumental variables methods were close to 0, although with wide CIs. CONCLUSIONS: CRP levels are associated with blood pressure, pulse pressure, and hypertension, but adjustment for life course confounding and a Mendelian randomization approach suggest the elevated CRP levels do not lead to elevated blood pressure.

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PubMed2005

Social, behavioral, and metabolic determinants of plasma viscosity in the Whitehall II Study.

PURPOSE: To examine the social, biological, and metabolic associations of plasma viscosity in a large epidemiological study. METHODS: Plasma viscosity was measured from 4548 men and 1837 women that took part in the fifth phase of the Whitehall II Study (1997-1999). Employment grade was used as a measure of social position. RESULTS: A strong inverse relation between employment grade and plasma viscosity was evident (p < 0.0001). This employment grade gradient was apparent overall, and among non-smokers and when participants with poor health were removed from the analyses. Plasma viscosity was associated with a number of biological factors that are themselves socially determined, including fibrinogen (p < 0.001), triglycerides (p < 0.001), fasting insulin (p < 0.001), and height (p < 0.001). Associations with smoking and alcohol intake were apparent in women. In men a U-shaped curve was apparent such that those drinking between 11 and 24 units/week had the lowest plasma viscosity. Alcohol intake, physical activity, and smoking explained 18% of the grade gradient in men and 40% in women while the biological factors examined accounted for 35% in men and 40% in women. CONCLUSION: There is a grade gradient in plasma viscosity which was not fully explained by health related behaviors or measured risk factors for CHD. These data suggest that additional factors that contribute to the rheological properties of plasma may contribute to the explanation for social inequalities in cardiovascular disease.

Adult↗

PubMed2005

The metabolic syndrome and insulin resistance: relationship to haemostatic and inflammatory markers in older non-diabetic men.

AIMS: We have examined the cross-sectional relationship between insulin resistance, the metabolic syndrome and haemostatic and inflammatory markers. METHODS AND RESULTS: We carried out the study in 2722 non-diabetic men aged 60-79 years with no history of coronary heart disease or stroke and who were not on warfarin treatment, drawn from general practices in 24 British towns. Insulin resistance (HOMA) was significantly associated with increased inflammatory markers (C-reactive protein (CRP), white cell count), coagulation factors VII-IX, von Willebrand factor (VWF) and tissue plasminogen activator (t-PA) antigens (markers of endothelial dysfunction) and blood viscosity after adjustment for age, smoking, physical activity, alcohol intake and waist circumference. Relationships with fibrinogen and fibrin D-dimer were weak. The relationship between HOMA and CRP was abolished after adjustment for t-PA. The prevalence of the metabolic syndrome was similar using World Health Organization (WHO) and National Cholesterol Education Program definitions (26.7% and 27.0%) but associations between the metabolic syndrome and increased haemostatic markers, particularly for raised factor VIII and VWF were stronger using WHO criteria. CONCLUSION: Insulin resistance and the metabolic syndrome showed significant associations with markers of haemostasis and inflammation, which may be relevant to their associations with cardiovascular disease.

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