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Biomedical subjects

G D Lowe

Publications and source records attributed to G D Lowe.

At least 55 records · Page 3Linked to original sources

Lifestyle and hemostatic risk factors for ischemic heart disease : the Caerphilly Study.

We have recently shown that fibrin D-dimer, tissue plasminogen activator (tPA) antigen, von Willebrand factor antigen, fibrinogen, plasma viscosity, and white cell count are associated with subsequent ischemic heart disease (IHD) in men aged 49 to 65 years in the Caerphilly Study from South Wales. We now report the contribution of major lifestyle factors to plasma levels of these new risk predictors for IHD. Results were available for up to 2188 men. The contribution of factors associated with lifestyle (smoking, alcohol, body mass index, leisure and work activity, social class, and use of prescribed medicines) to variation in plasma levels of 8 hemostatic variables was examined. All results were adjusted for other lifestyle variables, age, and time of day. Most hemostatic variables increased with age and smoking habit. Increasing levels of alcohol consumption were associated with increases in tPA and plasminogen activator inhibitor (PAI-1) activity and with decreases in fibrinogen and white cell count. tPA, PAI-1, fibrinogen (nephelometric), and viscosity were positively associated with body mass index. Increasing levels of leisure activity were inversely associated with D-dimer, von Willebrand factor, nephelometric fibrinogen, and viscosity. Use of prescribed medicines (a marker for chronic illness) was associated with adverse levels of D-dimer, fibrinogen, plasma viscosity, and white cell count. tPA, PAI-1, and plasma viscosity were associated with blood pressure, cholesterol, and triglycerides but not with lipoprotein(a) or homocysteine. We conclude that several lifestyle factors are associated with hemostatic risk predictors for IHD. Lifestyle modifications may reduce IHD risk partly by altering hemostatic function; large intervention studies are required to test this hypothesis.

Aged↗

Influence of high-density lipoprotein cholesterol and rheological factors on the sex difference in cardiovascular disease.

BACKGROUND: It is well established that the incidence of cardiovascular disease among men is higher than that among women. OBJECTIVE: To determine whether differences between men and women in terms of a range of conventional and rheological risk factors could explain this sex difference. DESIGN: This was a population-based cohort study (the Edinburgh Artery Study). METHODS: Men and women aged 55-74 years (n = 1592) were selected at random from the general population of Edinburgh and followed up for 5 years. Baseline cardiovascular risk factors were measured and related to incidence of disease among men and women. RESULTS: Men had higher levels of cigarette smoking, haematocrit and blood viscosity and lower levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and plasma fibrinogen than did women. The incidences of cardiovascular events among men and women were 48.3 and 26.1 per 1000 person-years, respectively. Adjustment for level of HDL cholesterol reduced the male:female ratio for sex-specific incidence rates of cardiovascular events from 1.80 [95% confidence interval (CI) 1.43-2.27] to 1.34 (95% CI 1.04-1.73). This reduction was partially reversed after further adjustment for the other cardiovascular risk factors. The impact of blood viscosity, plasma viscosity and plasma level of fibrinogen on the risk of cardiovascular disease was higher for men than it was for women (multivariate relative risk for blood viscosity were 1.24, 95% CI 1.08-1.43, for men and 0.81, 95% CI 0.61-1.06, for women). CONCLUSIONS: Levels of HDL cholesterol levels in women being higher than those in men may explain some, but not all, of the sex difference in incidence of cardiovascular disease. Greater susceptibility of men to rheological factors might also be important.

Age Distribution↗

Effects of weaning age and diet on growth and carcass characteristics in steers.

Two experiments were conducted to determine the effects of diet on growth of steers weaned at approximately 100 vs 205 d of age. In Exp. 1, a 2 x 2 x 2 factorial experiment was conducted using 78 Angus crossbred cow-calf pairs. The factors examined were age at weaning (early, at 103+/-3 d [EW] vs normal, at 203+/-3 d [NW]), feeding strategy (ad libitum vs postweaning programmed intake), and dietary CP concentration (100 vs 120% of NRC [1984] recommended levels). Early-weaned calves had a greater (P < .001) ADG than NW calves from 103 to 203 d and reached market weight at 385 d vs 418 d for NW calves (P < .001). Likewise, steers offered feed for ad libitum consumption reached market weight at 394 d, compared with 409 d for programmed-intake steers (P < .05). In Exp. 2, 64 Angus crossbred steers were either weaned at 93+/-3 d and fed one of four diets, weaned at 210+/-3 d without access to creep feed, or weaned at 210+/-3 d with access to creep feed for 60 d prior to weaning. Early-weaned calves were heavier (P < .01) than NW calves at 210 d if fed either 100 or 90% concentrate diets, and they had greater (P < .001) backfat thickness at 210 d but no difference (P > .10) in longissimus muscle area compared to EW calves fed a 60% concentrate diet. At slaughter, 80 to 100% of steers on all treatments graded low Choice or higher. Feeding high-concentrate diets to EW beef calves accelerated growth rate and fat deposition early in the feeding period and may be a way to provide young cattle for a high-quality beef market.

Age Factors↗

Plasma fibrinogen, haemostatic factors and prediction of peripheral arterial disease in the Edinburgh Artery Study.

The role of fibrinogen and other haemostatic factors in prediction of peripheral arterial disease (PAD) has not been established. We examined the associations of plasma fibrinogen, von Willebrand Factor (vWF), tissue plasminogen activator (t-PA) antigen, fibrin D-dimer, and factor VII with the development and clinical progression of PAD. In the Edinburgh Artery Study, 1592 men and women, aged between 55 and 74 years, were followed prospectively over 5 years to detect the onset of PAD, and the deterioration of established PAD. At baseline, 418 individuals had evidence of PAD and 60 (14.4%) subsequently deteriorated. 1080 subjects had no baseline disease, but 59 (5.5%) developed PAD during follow-up. Median levels of fibrinogen and vWF were higher in the group developing disease compared with the group which did not (2.78 g/l versus 2.57 g/l, P< or =0.01; 116 IU/dl versus 104 IU/dl, P< or =0.05; respectively). After adjusting for age and sex, fibrinogen (P< or =0.01) and vWF (P< or =0.05) were significantly associated with the risk of developing PAD. The association between fibrinogen and development of disease remained after adjusting for cardiovascular risk factors and baseline ischaemic heart disease (relative risk, 1.35, 95% confidence interval, 1.05, 1.73; P< or =0.05). None of the haemostatic factors were significantly associated with progression of PAD. In conclusion, plasma fibrinogen levels are related to the future onset of PAD, providing further evidence of a possible role of elevated fibrinogen in the development of atherosclerotic disease.

Aged↗

Immunoradiometric assay of circulating C-reactive protein: age-related values in the adult general population.

BACKGROUND: : Increased values of C-reactive protein (CRP), the classical acute phase protein, within the range below 5 mg/L, previously considered to be within the reference interval, are strongly associated with increased risk of atherothrombotic events, and are clinically significant in osteoarthritis and neonatal infection. METHODS: : A robust new polyclonal-monoclonal solid- phase IRMA for CRP was developed, with a range of 0.05-10.0 mg/L. RESULTS: : Plasma CRP values in general adult populations from Augsburg, Germany (2291 males and 2203 females; ages, 25-74 years) and Glasgow, Scotland (604 males and 650 females; ages, 25-64 years) were very similar. The median CRP approximately doubled with age, from approximately 1 mg/L in the youngest decade to approximately 2 mg/L in the oldest, and tended to be higher in females. CONCLUSION: : This extensive data set, the largest such study of CRP, provides valuable reference information for future clinical and epidemiological investigations.

Adult↗

Blood interactions with plasticized poly(vinyl chloride): relevance of plasticizer selection.

An investigation has been made of blood interactions with plasticized poly(vinyl chloride) (PVC) biomaterials in tubular form, taking into account the influence on the blood response of the polymer, antithrombotic agent, blood condition and test procedure. In vitro and ex vivo procedures were used to achieve a comparison between PVC plasticized with di- (2-ethylhexyl)phthalate (DEHP) and with tri-(2-ethylhexyl)trimellitate (TEHTM). The blood response was monitored in terms of the measurement of fibrinogen adsorption capacity, thrombin-antithrombin III complex (TAT) and the complement component C3a. Surface characterization of the polymers was performed by X-ray photoelectron spectroscopy (XPS). The data obtained indicate that in comparison with DEHP-PVC, there is a higher reactivity for TEHTM-PVC, which correlates with the plasticizer distribution at the polymer surface.

Journal Article↗

Associations of blood rheology and interleukin-6 with cardiovascular risk factors and prevalent cardiovascular disease.

Haemorheological variables (whole-blood, plasma and relative blood viscosity, haematocrit, red cell aggregation, white cell count and fibrinogen) were measured in 753 men and 821 women aged 25-74 years, and related to cardiovascular risk factors and prevalent cardiovascular disease (CVD). Men had higher levels than women of blood viscosity, haematocrit, corrected viscosity and relative viscosity. Post-menopausal women had higher levels than pre-menopausal women of blood viscosity, haematocrit, corrected blood viscosity, plasma viscosity and fibrinogen: each of these differences was completely or partly abolished by use of hormone replacement therapy. Serum total cholesterol, triglycerides, diastolic blood pressure, body mass index and smoking markers showed positive associations with most rheological variables, whereas HDL-cholesterol, plasma vitamin C and social class showed inverse associations. Rheological variables were associated with prevalent CVD after age-adjustment. However, after multiple risk factor adjustment only plasma viscosity and red cell aggregation showed significant (P<0.04) associations in both men and women (comparing top to bottom quarters). Plasma interleukin-6 (measured in a 25% subsample of 196 men and 221 women) correlated significantly with age, fibrinogen, white cell count, plasma and blood viscosity, current smoking, and (in men) with low serum vitamin C levels; but not with other major risk factors or with prevalent cardiovascular disease.

Adult↗

The role of haematological factors in diabetic peripheral arterial disease: the Edinburgh artery study.

The relationship between haematological factors and peripheral arterial disease (PAD) among diabetics has not been widely examined. 1592 men and women aged 55-74 years were selected from the general population. They underwent an assessment for PAD and a glucose tolerance test. 288 subjects (18.7%) were identified as having diabetes or impaired glucose tolerance (IGT). Among the diabetes/IGT group, median levels of fibrinogen, von Willebrand factor (VWF), tissue plasminogen activator (t-PA), fibrin D-dimer and plasma viscosity were higher in subjects with PAD than those without PAD (P </= 0.05). The prevalence of PAD was higher in those with diabetes/IGT (20.6%) compared to those with normal glucose tolerance (12.5%) (odds ratio 1.64; 95% CI 1.17, 2.31). After separate adjustment for fibrinogen, VWF, t-PA, fibrin D-dimer, leucocyte elastase, plasma viscosity and haematocrit, those with diabetes/IGT no longer had a significantly higher risk of PAD compared to those with a normal glucose tolerance test. Simultaneous adjustment for the first four of these haematological factors reduced the risk of PAD among subjects with diabetes/IGT to 1.11 (95% CI 0.76, 1.63). Increased levels of haemostatic factors may partly explain the higher prevalence of PAD in diabetic/IGT subjects compared to normal glucose-tolerant subjects. Future randomized controlled trials involving the indirect lowering of levels of haematological factors should help to explain whether the associations reported here are of causal significance.

Aged↗

Rheological influences on thrombosis.

Blood flow plays important roles in the localization and morphology of thrombosis within the circulation. Blood flow properties (rheological variables) are associated with thrombotic risk factors and thrombotic risk; conversely their modification may reduce thrombotic risk.

Animals↗

Relationship between smoking and cardiovascular risk factors in the development of peripheral arterial disease and coronary artery disease: Edinburgh Artery Study.

AIMS: The aim was to determine whether the effect of smoking on the development of peripheral or coronary artery disease might be mediated by other cardiovascular risk factors, including dietary antioxidant vitamin intake, serum low and high density lipoproteins, blood pressure, plasma fibrinogen, blood viscosity and markers of endothelial disturbance and fibrin turnover. METHODS AND RESULTS: 1592 men and women aged 55-74 years were selected at random from 11 general practices in Edinburgh, Scotland and followed-up for 5 years. The incidences of peripheral arterial disease and coronary artery disease were 5.1% and 11.1%, respectively. Both conditions were more common in moderate and heavy smokers than in never smokers: cigarette smoking was a stronger risk factor for peripheral arterial disease than for coronary artery disease. Smoking was associated with reduced dietary antioxidant vitamin intake, serum high density lipoprotein cholesterol and diastolic blood pressure and with increased alcohol intake, serum triglycerides, blood viscosity, plasma fibrinogen, and markers of endothelial disturbance (tissue plasminogen activator and von Willebrand factor antigens). Simultaneous adjustment for these risk factors reduced the relative risk of peripheral arterial disease only slightly, from 3.94 (95% CI 2.04, 7.62) to 2.72 (95% CI 1.13, 6.53) in heavy smokers and from 1.87 (95% CI 0.91, 3.85) to 1.70 (95% CI 0.72, 3.99) in moderate smokers. Similar adjustment also had little effect on the risk of coronary artery disease associated with smoking. CONCLUSION: The combined effect of smoking on the cardiovascular risk factors studied may explain part of its influence on peripheral and coronary arterial disease, but the majority of the effect appears to be due to other mechanisms.

Aged↗

Carotid plaque, intima media thickness, cardiovascular risk factors, and prevalent cardiovascular disease in men and women: the British Regional Heart Study.

BACKGROUND AND PURPOSE: B-mode ultrasound is a noninvasive method of examining the walls of peripheral arteries and provides measures of the intima-media thickness (IMT) at various sites (common carotid artery, bifurcation, internal carotid artery) and of plaques that may indicate early presymptomatic disease. The reported associations between cardiovascular risk factors, clinical disease, IMT, and plaques are inconsistent. We sought to clarify these relationships in a large, representative sample of men and women living in 2 British towns. METHODS: The study was performed during 1996 in 2 towns (Dewsbury and Maidstone) of the British Regional Heart Study that have an approximately 2-fold difference in coronary heart disease risk. The male participants were drawn from the British Regional Heart Study and were recruited in 1978-1980 and form part of a national cohort study of 7735 men. A random sample of women of similar age to the men (55 to 77 years) was also selected from the age-sex register of the general practices used in the original survey. A wide range of data on social, lifestyle, and physiological factors, cardiovascular disease symptoms, and diagnoses was collected. Measures of right and left common carotid IMT (IMTcca) and bifurcation IMT (IMTbif) were made, and the arteries were examined for plaques 1.5 cm above and below the flow divider. RESULTS: Totals of 425 men and 375 women were surveyed (mean age, 66 years; range, 56 to 77 years). The mean (SD) IMTcca observed were 0. 84 (0.21) and 0.75 (0.16) mm for men and women, respectively. The mean (SD) IMTbif were 1.69 (0.61) and 1.50 (0.77) mm for men and women, respectively. The correlation between IMTcca and IMTbif was similar in men (r=0.36) and women (r=0.38). There were no differences in mean IMTcca or IMTbif between the 2 towns. Carotid plaques were very common, affecting 57% (n=239) of men and 58% (n=211) of women. Severe carotid plaques with flow disturbance were rare, affecting 9 men (2%) and 6 women (1.6%). Plaques increased in prevalence with age, affecting 49% men and 39% of women aged <60 years and 65% and 75% of men and women, respectively, aged >70 years. Plaques were most common among men in Dewsbury (79% affected) and least common among men in Maidstone (34% affected). IMTcca showed a different pattern of association with cardiovascular risk factors from IMTbif and was associated with age, SBP, and FEV1 but not with social, lifestyle, or other physiological risk factors. IMTbif and carotid plaques were associated with smoking, manual social class, and plasma fibrinogen. IMTbif and carotid plaques were associated with symptoms and diagnoses of cardiovascular diseases. IMTbif associations with cardiovascular risk factors and prevalent cardiovascular disease appeared to be explained by the presence of plaques in regression models and in analyses stratified by plaque status. CONCLUSIONS: IMTcca, IMTbif, and plaque are correlated with each other but show differing patterns of association with risk factors and prevalent disease. IMTcca is strongly associated with risk factors for stroke and with prevalent stroke, whereas IMTbif and plaque are more directly associated with ischemic heart disease risk factors and prevalent ischemic heart disease. Our analyses suggest that presence of plaque, rather than the thickness of IMTbif, appears to be the major criterion of high risk of disease, but confirmation of these findings in other populations and in prospective studies is required. The association of fibrinogen with plaque appears to be similar to its association with incident cardiovascular disease. Further work elucidating the composition of plaques using ultrasound imaging would be helpful, and more data, analyzed to distinguish plaque from IMTbif and IMTcca, are required to understand the significance of thicker IMT in the absence of plaque.

Age Distribution↗

Effects of corn processing and dietary fiber source on feedlot performance, visceral organ weight, diet digestibility, and nitrogen metabolism in lambs.

In Exp. 1, early-weaned Targhee and Polypay crossbred lambs (60 ewes and 66 rams; initial BW 24 +/- 1.0 kg) were used in a 2 x 3 factorial experiment to determine the effects of corn processing (whole shelled corn [WSC] or ground and pelleted corn [GC]) in combination with supplemental fiber (none [control]; soybean hulls, SBH [highly digestible]; or peanut hulls, PH [highly indigestible]) on DMI, ADG, feed efficiency, and visceral organ weight. For the total trial, WSC resulted in a 4% increase (P < .01) in ADG vs GC, and supplemental fiber resulted in increased (P < .01) DMI and ADG vs the control diet. Experiment 2 was conducted using 12 Targhee and Polypay crossbred wether lambs (initial BW 25 +/- 7 kg) to determine the effects of corn processing and fiber source in high-concentrate diets on diet digestibility and N retention using the same diets as in Exp. 1. Lambs fed WSC had greater (P < .001) apparent N digestion, true N digestion, and N retention (P < .01) than those fed GC. The apparent digestibilities of DM, OM, and NDF were greater (P < .001) for WSC than for GC diets. Peanut hulls resulted in decreased (P < .01) DM, OM, and NDF apparent digestibilities compared with the control and SBH diets. Starch digestion was not affected (P > .10) by diet. Whole corn resulted in improved DM, OM, NDF, and N digestibility compared with GC. Overall, both the SBH and PH diets resulted in greater DMI and ADG than the control diet, which lacked supplemental fiber.

Animal Feed↗

Energy source and ionophore supplementation effects on lamb growth, carcass characteristics, visceral organ mass, diet digestibility, and nitrogen metabolism.

In Exp. 1, 72 Targhee lambs (initial BW 22.1+/-.3 kg) were used to determine the effects of energy source (alfalfa pasture vs limit-fed, all-concentrate) and ionophore addition on performance, visceral organ mass, and carcass characteristics. There were no differences (P > . 10) in ADG or gain/ feed due to ionophore supplementation. Lambs that grazed alfalfa had greater (P < .05) liver, omasum, abomasum, small intestine, cecum, and large intestine weights than did lambs fed the concentrate diet. Lambs fed the concentrate diet had greater (P < .01) hot carcass weights, larger (P < .01) loin eye areas, and greater (P < .001) dressing percentages than lambs that grazed alfalfa. In Exp. 2, lambs offered the concentrate diet had greater (P < .001) DM and OM digestibilities than lambs offered alfalfa (89.5 and 91.1 vs 72.4 and 74.2%, respectively). Apparent and true N digestibilities were greater (P < .001) for the concentrate diet than for alfalfa (90.9 and 101.7 vs 77.7 and 91.9%, respectively). Likewise, grams of N retained per day were twice as great (P < .001) with the concentrate diet than with alfalfa (14.9 vs 6.0 g/ d). The greater visceral organ mass and resulting increases in energy and protein requirements in lambs that grazed alfalfa were probably responsible for the lesser hot carcass weight and dressing percentage compared with lambs fed 100% concentrate.

Animal Feed↗

Acute renal failure complicating high-dose intravenous immunoglobulin therapy for acquired haemophilia.

Acquired haemophilia is a rare disorder requiring therapy to control bleeding and to suppress the inhibitory antibody. High-dose intravenous immunoglobulin is commonly used as part of immunosuppressive regimens for this condition. We describe the case of an elderly patient who developed acute oliguric renal failure as a result of intravenous immunoglobulin therapy. All patients receiving such treatment should have renal function carefully monitored both during and after the infusion.

Acute Kidney Injury↗

Factor VIII, von Willebrand factor and the risk of major ischaemic heart disease in the Caerphilly Heart Study.

The relationships of three measurements of the factor VIII/von Willebrand factor (VWF) complex (factor VIII activity, FVIIIc (one-stage assay); VWF antigen, VWF Ag (ELISA); and VWF activity, VWF act, measured by a recently-developed ELISA) to major ischaemic heart disease (IHD) events were studied in 1997 men aged 49-65 years, in the second phase of the Caerphilly Heart Study. These variables were related using logistic regression analysis to myocardial infarction or IHD death, which occurred in 129 men during an average follow-up period of 61 months. All three measurements were highly correlated (r = 0.63-0.77), and each was significantly associated with incident major IHD on univariate analyses (relative odds in highest fifth compared to lowest fifth, 1.68-1.90; P = 0.028-0.006) and on multivariate analyses adjusting for major IHD risk factors and for baseline IHD. Neither FVIIIc nor VWF act was significantly related to incident IHD following adjustment for VWF Ag. We therefore suggest that the associations between these three measurements of the factor VIII/VWF complex and incident IHD might have at least three explanations: VWF Ag is a marker of arterial endothelial disturbance; VWF act promotes platelet adhesion/aggregation and hence the platelet component of arterial thrombosis; and FVIIIc promotes fibrin formation and hence the fibrin component of arterial thrombosis.

Enzyme-Linked Immunosorbent Assay↗

Fibrinogen, factor VII and PAI-1 genotypes and the risk of coronary and peripheral atherosclerosis: Edinburgh Artery Study.

There are now many epidemiological studies that have shown a relationship between haemostatic factors and subsequent risk of both coronary and peripheral arterial disease. However, there is less information on the association between genetic variation in these factors and the risks of coronary and peripheral arterial disease. As part of the five-year follow-up of the Edinburgh Artery Study, polymorphisms of the fibrinogen (-455G/A), factor VII (R/Q353) and PAI-1 (HindIII) genes were measured in men and women aged 60-79 years, together with their plasma levels. Using widely accepted criteria, 88 subjects were identified as having peripheral arterial disease (PAD), 195 having coronary artery disease (CAD) and 423 subjects comprised a "healthy" group. The -455AA genotype of the fibrinogen gene was found to be more frequent among those subjects with PAD. This genotype also showed the highest plasma fibrinogen levels in both disease groups and in the healthy group. Using logistic regression, after adjustment for age, sex, smoking and plasma level, the -455AA genotype was associated with over twice the risk of PAD compared with the -455GG genotype, the odds ratio reaching marginal significance (p < or = 0.10). Combining those with genotype -455AA with the heterozygotes in order to increase the power of the study resulted in a more significant multiple-adjusted risk of PAD (p < or = 0.05). These data provide evidence that a polymorphism of the P fibrinogen gene is associated with an increased risk of peripheral atherosclerosis.

Aged↗

Prediction of deep vein thrombosis after elective hip replacement surgery by preoperative clinical and haemostatic variables: the ECAT DVT Study. European Concerted Action on Thrombosis.

The European Concerted Action on Thrombosis (ECAT) DVT Study was a collaborative study of preoperative haemostatic tests in prediction of DVT (diagnosed by routine bilateral venography) after elective hip replacement. 480 patients were recruited in 11 centres across Europe. Clinical risk factors were assessed, and stored citrated plasma aliquots were centrally assayed for 29 haemostatic factors according to the ECAT methodology. 120 (32%) of 375 evaluable patients had DVT, and 41 (11%) had proximal DVT. Among clinical variables, DVT was significantly associated with increased age, obesity, and possibly non-use of stockings. Of the 29 haemostatic factors, mean preoperative levels were significantly higher in patients with subsequent DVT (on univariate analyses) for factor VIII activity, prothrombin fragment F1+2, thrombin-antithrombin complexes, and fibrin D-dimer; and significantly lower for APTT and APC sensitivity ratio. Factor V Leiden was also associated with DVT. Most of these variables were also associated with age, while D-dimer was higher in patients with varicose veins. On multivariate analyses including clinical variables, only a shorter APTT (locally but not centrally performed) and APC resistance showed a statistically significant association with DVT. We conclude that (a) DVT is common after elective hip replacement despite prophylaxis; (b) the study provides some evidence that DVT is associated with a preoperative hypercoaguable state; and (c) preoperative haemostatic tests do not add significantly to prediction of DVT from clinical variables, with the possible exception of APC resistance.

Aged↗

Activated protein C resistance and the FV:R506Q mutation in a random population sample--associations with cardiovascular risk factors and coagulation variables.

Activated protein C (APC) resistance, defined as a low APC ratio, is associated with the factor V mutation R506Q (factor V Leiden). APC ratio may also be influenced by other clinical and coagulation variables, which we studied in 460 men and 495 women aged 25-74 years, from a random population sample (Glasgow MONICA Survey). APC ratio correlated positively with APTT; and inversely with factor VIIIc, factor IXc, antithrombin activity, prothrombin F1+2 fragment, and thrombin-antithrombin complexes; but not with other coagulation variables. APC ratio decreased with age, but APTT did not. APC ratio and APTT were significantly lower in women versus men, and were significantly lower in users of oral contraceptives or hormone replacement therapy. The FV:R506Q mutation (prevalence 2.5%) was associated with lower APC ratio and protein C and S activities and with higher factor VIIIc levels; but not with increases in F1+2 fragment or thrombin-antithrombin complexes. APC ratio correlated inversely with total cholesterol and diastolic blood pressure; and in women with triglycerides, systolic blood pressure, and body mass index. Obesity was associated with a significantly lower APC ratio. In contrast, smoking markers correlated positively with APC ratio in men. These associations of APC ratio may be relevant to the increased risks of venous thrombosis with age, female sex, oestrogen use, obesity and high factor VIIIc levels. The association of APC resistance with elevated plasma levels of coagulation markers suggests that this phenotype represents an in vivo hypercoagulable state.

Activated Protein C Resistance↗