Plasma viscosity and the risk of coronary heart disease: results from the MONICA-Augsburg Cohort Study, 1984 to 1992

Plasma viscosity is determined by various macromolecules, eg, fibrinogen, immunoglobulins, and lipoproteins. It may therefore reflect several aspects involved in cardiovascular diseases, including the effects of classic risk factors, hemostatic disturbances, and inflammation. We examined the association of plasma viscosity with the incidence of a first major coronary heart disease event (CHD; fatal and nonfatal myocardial infarction and cardiac death; n=50) in 933 men aged 45 to 64 years of the MONICA project of Augsburg, Germany. The incidence rate was 7.23 per 1000 person-years (95% confidence interval [CI], 5.37 to 9.53), and the subjects were followed up for 8 years. All suspected cases of an incident CHD event were classified according to the MONICA protocol. There was a positive and statistically significant unadjusted relationship between plasma viscosity and the incidence of CHD. The relative risk of CHD events associated with a 1-SD increase in plasma viscosity (0.070 mPa x s) was 1.60 (95% CI, 1.25 to 2.03). After adjustment for age, total cholesterol, high density lipoprotein cholesterol, smoking, blood pressure, and body mass index, the relative risk was reduced only moderately (1.42; 95% CI, 1.09 to 1.86). The relative risk of CHD events for men in the highest quintile of the plasma viscosity distribution in comparison with the lowest quintile was 3.31 (95% CI, 1.19 to 9.25) after adjustment for the aforementioned variables. A large proportion of events (40%) occurred among men in the highest quintile. These findings suggest that plasma viscosity may have considerable potential to identify subjects at risk for CHD events.     

Erythrocyte sedimentation rate and coronary heart disease: the NHANES I Epidemiologic Follow-up Study

Erythrocyte sedimentation rate (ESR) is a simple and relatively inexpensive laboratory test. Data were examined to determine whether elevated ESR was a predictor of CHD incidence and death in a large U.S. national sample of persons aged 45-74 at baseline. In the NHANES I Epidemiologic Follow-up Study cohort, white men aged 45-64 years with ESR in the upper quintile at baseline had increased incidence of CHD (RR = 1.73, 95% CL 1.12, 2.68) over a 15 year follow-up after controlling multiple risk factors compared to white men with ESR in the lowest quintile. Furthermore, men aged 45-64 with ESR in the upper quintile had more than twice the risk of CHD death (RR = 2.73, 95% CL 1.21, 6.15) of men with ESR in the lowest quintile after adjusting other risk factors. No significant associations were seen in white women. The mechanism of this association is unclear. Further studies are needed to replicate this finding and elucidate the mechanism for this association in longitudinal studies in which plasma fibrinogen, HDL cholesterol, as well as ESR are measured.     

Do cardiovascular risk factors explain the relation between socioeconomic status, risk of all-cause mortality, cardiovascular mortality, and acute myocardial infarction?

Much remains to be understood about how low socioeconomic status (SES) increases cardiovascular disease and mortality risk. Data from the Kuopio Ischemic Heart Disease Risk Factor Study (1984-1993) were used to estimate the associations between acute myocardial infarction and income, all-cause mortality, and cardiovascular mortality in a population-based sample of 2,272 Finnish men, with adjustment for 23 biologic, behavioral, psychologic, and social risk factors. Compared with the highest income quintile, those in the bottom quintile had age-adjusted relative hazards of 3.14 (95% confidence interval (CI) 1.77-5.56), 2.66 (95% CI 1.25-5.66), and 4.34 (95% CI 1.95-9.66) for all-cause mortality, cardiovascular mortality, and AMI, respectively. After adjustment for risk factors, the relative hazards for the same comparisons were 1.32 (95% CI 0.70-2.49), 0.70 (95% CI 0.29-1.69), and 2.83 (95% CI 1.14-7.00). In the lowest income quintile, adjustment for risk factors reduced the excess relative risk of all-cause mortality by 85%, that of cardiovascular mortality by 118%, and that of acute myocardial infarction by 45%. These data show how the association between SES and cardiovascular mortality and all-cause mortality is mediated by known risk factor pathways, but full "explanations" for these associations will need to encompass why these biologic, behavioral, psychologic, and social risk factors are differentially distributed by SES.     

Intake of fatty acids and risk of coronary heart disease in a cohort of Finnish men. The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study

The relation of intakes of specific fatty acids and the risk of coronary heart disease was examined in a cohort of 21,930 smoking men aged 50-69 years who were initially free of diagnosed cardiovascular disease. All men participated in the Finnish Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study and completed a detailed and validated dietary questionnaire at baseline. After 6.1 years of follow-up from 1985-1988, the authors documented 1,399 major coronary events and 635 coronary deaths. After controlling for age, supplement group, several coronary risk factors, total energy, and fiber intake, the authors observed a significant positive association between the intake of trans-fatty acids and the risk of coronary death. For men in the top quintile of trans-fatty acid intake (median = 6.2 g/day), the multivariate relative risk of coronary death was 1.39 (95% confidence interval (CI) 1.09-1.78) (p for trend = 0.004) as compared with men in the lowest quintile of intake (median = 1.3 g/day). The intake of omega-3 fatty acids from fish was also directly related to the risk of coronary death in the multivariate model adjusting also for trans-saturated and cis-monounsaturated fatty acids (relative risk (RR) = 1.30, 95% CI 1.01-1.67) (p for trend = 0.06 for men in the highest quintile of intake compared with the lowest). There was no association between intakes of saturated or cis-monounsaturated fatty acids, linoleic or linolenic acid, or dietary cholesterol and the risk of coronary deaths. All the associations were similar but somewhat weaker for all major coronary events.     

A prospective study of positive psychological well-being and coronary heart disease.

Objective: Research suggests that positive psychological well-being is associated with cardiovascular health. However, much of this research uses elderly samples and has not determined the pathways by which psychological well-being influences cardiovascular disease or whether effects are similar for men and women. This study investigates the association between two aspects of well-being (emotional vitality and optimism) and coronary heart disease (CHD) in a sample of middle-aged men and women, and considers potential mediating factors. Method: Between 1991 and 1994, well-being and coronary risk factors were assessed among 7,942 individuals without a prior cardiovascular event from the Whitehall II cohort. Incident CHD (fatal CHD, first nonfatal myocardial infarction, or first definite angina) was tracked during 5 person-years of follow-up. Results: Positive psychological well-being was associated with reduced risk of CHD with an apparent threshold effect. Relative to people with the lowest levels of well-being, those with the highest levels had minimally adjusted hazard ratios of 0.74, 95% confidence interval [0.55, 0.98] for emotional vitality and 0.73, 95% confidence interval [0.54, 0.99] for optimism. Moreover, the association was strong for both genders and was only weakly attenuated when accounting for ill-being. Neither health-related behaviors nor biological factors explained these associations. Conclusions: Positive psychological well-being was associated with a modest, but consistent reduced risk of incident CHD. The relationship was comparable for men and women, and was maintained after controlling for cardiovascular risk factors and ill-being. Additional research is needed to identify underlying mechanisms and investigate whether interventions to increase well-being may enhance cardiovascular health. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Association of coronary heart disease incidence with carotid arterial wall thickness and major risk factors: the Atherosclerosis Risk in Communities (ARIC) Study, 1987-1993

Few studies have determined whether greater carotid artery intima-media thickness (IMT) in asymptomatic individuals is associated prospectively with increased risk of coronary heart disease (CHD). In the Atherosclerosis Risk in Communities Study, carotid IMT, an index of generalized atherosclerosis, was defined as the mean of IMT measurements at six sites of the carotid arteries using B-mode ultrasound. The authors assessed its relation to CHD incidence over 4-7 years of follow-up (1987-1993) in four US communities (Forsyth County, North Carolina; Jackson, Mississippi; Minneapolis, Minnesota; and Washington County, Maryland) from samples of 7,289 women and 5,552 men aged 45-64 years who were free of clinical CHD at baseline. There were 96 incident events for women and 194 for men. In sex-specific Cox proportional hazards models adjusted only for age, race, and center, the hazard rate ratio comparing extreme mean IMT (> or = 1 mm) to not extreme (< 1 mm) was 5.07 for women (95% confidence interval 3.08-8.36) and 1.85 for men (95% confidence interval 1.28-2.69). The relation was graded (monotonic), and models with cubic splines indicated significant nonlinearity. The strength of the association was reduced by including major CHD risk factors, but remained elevated at higher IMT. Up to 1 mm mean IMT, women had lower adjusted annual event rates than did men, but above 1 mm their event rate was closer to that of men. Thus, mean carotid IMT is a noninvasive predictor of future CHD incidence.     

Options for treatment of persistent aneurysm perfusion after endovascular repair

The association between serum uric acid level and risk of coronary heart disease (CHD) over 21 years was investigated among 6411 middle-aged Japanese-American men who were participants in the Honolulu Heart Program. In an age-stratified Cox regression model, high serum uric acid (quartile 4 [>6.7 mg/dl], relative to quartile 1 [<5.0 mg/dl]) was a significant predictor of definite CHD (RR = 1.33; 95% confidence interval = 1.08-1.63; p = 0.006). However, when adjustment for confounders (body mass index, heavy alcohol consumption, triglycerides, diastolic blood pressure, blood glucose, and the ratio of animal to vegetable protein) was made, the association of high uric acid with coronary events was substantially reduced and became nonsignificant (RR = 1.14; 95% confidence interval = 0.92-1.42; p = 0.21). There was a significant interaction between serum uric acid and drinking status (P = 0.03). Thus, the risk of definite CHD associated with high urate levels (quartile 4), relative to low levels (quartile 1), was elevated in the abstainers (RR = 1.40; 95% confidence interval = 1.01-1.93; p = 0.02), but not in light and moderate drinkers (RR = 1.1 1; 95% confidence interval = 0.79-1.55; p = 0.58) or among the heavy drinkers (>40 ml of ethanol/day; RR = 0.57; 95% confidence interval = 0.27-1.21; p = 0.08). It is concluded that elevated uric acid may be associated with higher CHD among alcohol abstainers. Whether raised urate is an etiological factor for CHD or a manifestation of existing arterial disease in nondrinkers deserves further investigation.     

Coagulation factor VII and the risk of coronary heart disease in healthy men

Numerous investigations have demonstrated the role of thrombus formation in the pathogenesis of coronary heart disease (CHD). A tendency to thrombosis may also be indicated by elevated levels of coagulation factor VII clotting activity (FVIIc). Significant associations of FVIIc with increased coronary risk, however, have been found only in the Northwick Park Heart Study. Here we present the results of the 8-year follow-up of FVIIc measurements in 2780 healthy men of the Prospective Cardiovascular Münster study. In the study population (age at entry, 49.3 +/- 6.1 years, mean +/- SD), 130 CHD events occurred during follow-up. FVIIc was significantly higher in subjects with coronary events than in those without (112.4 +/- 20.1% vs 108.7 +/- 21.4%, P = .023). Compared with individuals without coronary events, FVIIc was not significantly higher in men with nonfatal events (111.7 +/- 20.4%; P = .196, n = 93), but there was a tendency toward higher FVIIc activity in subjects with fatal events (114.6 +/- 19.5%; P = .076, n = 37). In the multiple logistic regression analysis, we did not find FVIIc to be an independent risk factor for CHD, and the significance of FVIIc disappeared after total cholesterol, LDL-cholesterol, and triglycerides were taken into account. The increase in the number of CHD events through higher levels of FVIIc was more pronounced in the presence of additional cardiovascular risk factors: smoking; myocardial infarction events in family; angina pectoris; high levels of fibrinogen, total cholesterol, LDL cholesterol, and triglycerides; and a low level of HDL cholesterol. We conclude that FVIIc is a risk factor for CHD, especially in the presence of additional risk factors, and must be taken into account when assessing cardiovascular risk in men.     

Serum cholesterol level and mortality due to suicide and trauma in the Honolulu Heart Program

BACKGROUND: Recent results from cholesterol level-lowering trials and some, but not all, observational studies support an intriguing link between low or lowered serum cholesterol levels and violent death. The reasons behind this relationship are far from clear. METHODS: In this report, we further investigate this issue by assessing the relationship of baseline serum cholesterol levels with long-term risk of mortality due to trauma and suicide in a cohort of 7309 middle-aged Japanese-American men. RESULTS: After 23 years of follow-up, a total of 75 traumatic fatalities and 24 deaths by suicide were documented. Rather than an inverse relation, a positive association between serum cholesterol level and risk of suicide death was observed. After controlling for potential confounders, the relative risk of suicide associated with an increment of 0.98 mmol/L (38 mg/dL) in serum cholesterol level (1 SD) was 1.46 (95% confidence interval, 1.04 to 2.05; P = .02). Multivariate analysis of traumatic mortality failed to detect a relation with serum cholesterol level (relative risk = 0.89; 95% confidence interval, 0.70 to 1.13; P = .44). Heavy alcohol consumption (> 1200 mL of alcohol per month, top quintile) was an independent risk factor for trauma death relative to abstinence (relative risk = 1.86; 95% confidence interval, 1.07 to 3.22; P = .02). CONCLUSIONS: These findings contradict the hypothesis of an inverse relation between serum cholesterol level and suicide, but they support the hypothesis that heavy alcohol consumption is a risk factor for traumatic fatal events.     

Calcium intake and the incidence of forearm and hip fractures among men

High calcium intakes are thought to be associated with strong bones and lower risk of fractures. However, findings from epidemiologic studies have not been consistent. In addition, the vast majority of such studies were conducted among women, leading to a relative lack of data concerning men. The objective of this study therefore was to investigate the relation between adult calcium intake and risk of fractures among men in the Health Professionals Follow-up Study (HPFS). During 331,234 person-years of follow-up over an 8-y period, 201 forearm and 56 hip fractures due to low or moderate trauma were reported among 43,063 men 40-75 y of age in 1986 when they first completed a questionnaire about diet and lifestyle factors. After controlling for age, smoking status, body mass index (BMI), physical activity, alcohol consumption and total energy intake, the relative risk (RR) of forearm fractures for men in the highest quintile of calcium intake (from foods plus supplements) compared with those in the lowest quintile was 0.98 [95% confidence interval (CI) = 0.59-1.61; P for trend = 0.78]; for hip fractures, the comparable RR was 1.19 (95% CI = 0.42-3.35; P for trend = 0.58). Relative risks for consuming >2.5 glasses (600 mL) of milk per day compared with one (240 mL) or fewer per week were 1.06 (95% CI = 0.69-1.62; P for trend = 0.82) for forearm fractures and 0.97 (95% CI = 0.39-2.42; P for trend = 0.56) for hip fractures. In conclusion, these results do not support a relation between calcium intake and the incidence of forearm or hip fractures in men.     

Trends in the incidence of myocardial infarction and in mortality due to coronary heart disease, 1987 to 1994

BACKGROUND AND METHODS: To clarify the determinants of contemporary trends in mortality from coronary heart disease (CHD), we conducted surveillance of hospital admissions for myocardial infarction and of in-hospital and out-of-hospital deaths due to CHD among 35-to-74-year-old residents of four communities of varying size in the United States (a total of 352,481 persons in 1994). Between 1987 and 1994, we estimate that there were 11,869 hospitalizations for myocardial infarction (on the basis of 8572 hospitalizations sampled) and 3407 fatal coronary events (3023 sampled). RESULTS: The largest average annual decrease in mortality due to CHD occurred among white men (change in mortality, -4.7 percent; 95 percent confidence interval, -2.2 to -7.1 percent), followed by white women (-4.5 percent; 95 percent confidence interval, -0.7 to -8.2 percent), black women (-4.1 percent; 95 percent confidence interval, -10.3 to +2.5 percent), and black men (-2.5 percent; 95 percent confidence interval, -6.9 to +2.2 percent). Overall, in-hospital mortality from CHD fell by 5.1 percent per year, whereas out-of-hospital mortality declined by 3.6 percent per year. There was no evidence of a decline in the incidence of hospitalization for a first myocardial infarction among either men or women; in fact, such hospital admissions increased by 7.4 percent per year (95 percent confidence interval for the change, +0.5 to +14.8 percent) among black women and 2.9 percent per year (95 percent confidence interval, -3.6 to +9.9 percent) among black men. Rates of recurrent myocardial infarction decreased, and survival after myocardial infarction improved. CONCLUSIONS: From 1987 to 1994, we observed a stable or slightly increasing incidence of hospitalization for myocardial infarction. Nevertheless, there were significant annual decreases in mortality from CHD. The decline in mortality in the four communities we studied may be due largely to improvements in the treatment and secondary prevention of myocardial infarction.     

A prospective study of dietary calcium and other nutrients and the risk of symptomatic kidney stones

BACKGROUND: A high dietary calcium intake is strongly suspected of increasing the risk of kidney stones. However, a high intake of calcium can reduce the urinary excretion of oxalate, which is thought to lower the risk. The concept that a higher dietary calcium intake increases the risk of kidney stones therefore requires examination. METHODS: We conducted a prospective study of the relation between dietary calcium intake and the risk of symptomatic kidney stones in a cohort of 45,619 men, 40 to 75 years of age, who had no history of kidney stones. Dietary calcium was measured by means of a semiquantitative food-frequency questionnaire in 1986. During four years of follow-up, 505 cases of kidney stones were documented. RESULTS: After adjustment for age, dietary calcium intake was inversely associated with the risk of kidney stones; the relative risk of kidney stones for men in the highest as compared with the lowest quintile group for calcium intake was 0.56 (95 percent confidence interval, 0.43 to 0.73; P for trend, < 0.001). This reduction in risk decreased only slightly (relative risk, 0.66; 95 percent confidence interval, 0.49 to 0.90) after further adjustment for other potential risk factors, including alcohol consumption and dietary intake of animal protein, potassium, and fluid. Intake of animal protein was directly associated with the risk of stone formation (relative risk for men with the highest intake as compared with those with the lowest, 1.33; 95 percent confidence interval, 1.00 to 1.77); potassium intake (relative risk, 0.49; 95 percent confidence interval, 0.35 to 0.68) and fluid intake (relative risk, 0.71; 95 percent confidence interval, 0.52 to 0.97) were inversely related to the risk of kidney stones. CONCLUSIONS: A high dietary calcium intake decreases the risk of symptomatic kidney stones.     

Associations of urinary albumin excretion rate with vascular disease in europid nondiabetic subjects

Microalbuminuria and its association with vascular disease has previously been reported in nondiabetic individuals. The aims of this study were to determine whether there is a cross-sectional relationship between urinary albumin excretion rate and cardiovascular disease in nondiabetic subjects and to investigate hereditary predisposition to microalbuminuria by studying offspring of the main study population. Europid patients, aged 40-70 years, were randomly selected from a large inner-city general practice; there was a 62.6% attendance rate, and a study population of 959 remained after exclusions. Blood pressure, ankle systolic pressure, height, and weight were measured. Albumin excretion rate was calculated from overnight and morning urine collections. Venous blood was taken for lipids, fibrinogen, and factor VII; and resting electrocardiograms were carried out. Offspring (aged 15-40 years) of those found to be microalbuminuric were invited to attend for the same tests, and controls were selected by age and sex matching the parents. There was no association between parents' albumin excretion rate with that of their offspring, and there were no significant differences in albumin excretion rate between offspring subjects and their controls. There were no statistically significant associations of prevalent coronary heart disease (CHD) with albumin excretion rate or microalbuminuria in either sex [CHD in women: odds ratio (OR) 1.85; 95% confidence interval (CI) 0.19,9.0] [CHD in men: OR 2.13; 95% CI (0.64, 6.59)]. In women, there were significant associations between albumin excretion rate and peripheral vascular disease (positive) and fibrinogen (negative). Because established risk factors may not be as strongly associated with CHD in cross-sectional studies, we intend to follow this group prospectively.     

Assembly and activation of the intrinsic fibrinolytic pathway on the surface of human endothelial cells in culture

Factor XII has long been implicated in the intrinsic pathway of fibrinolysis, but the mechanism by which it triggers plasminogen activation and targets fibrinolysis has not been established. In the present study, the assembly and function of activated Factor XII (F.XIIa), prourokinase (pro-u-PA), high molecular weight kininogen (H-kininogen), and prekallikrein on human umbilical vein endothelial cells (HUVEC) was investigated. 125I-prekallikrein was shown to bind to HUVEC via receptor-bound H-kininogen in the presence of 50 microM ZnCl2. After the addition of F.XIIa, 78% of the 125I-prekallikrein initially bound to HUVEC was converted to 125I-kallikrein. However, only 6% of the HUVEC-bound 125I-pro-u-PA was thereby activated. This discrepancy was shown to be related to rapid dissociation (> 50% within 15 min) of prekallikrein/kallikrein, but not pro-u-PA, from HUVEC. Increasing the level of cell-bound kallikrein increased the portion of cell-bound pro-u-PA activated, indicating that their co-localization was important for this pathway. Finally, F.XIIa was shown to trigger plasminogen activation on HUVEC via this pathway. This assembly of reactants on the endothelium suggests a mechanism whereby local fibrinolysis may be triggered by blood coagulation.     

Association of fibrinogen, C-reactive protein, albumin, or leukocyte count with coronary heart disease: meta-analyses of prospective studies

CONTEXT: A large number of epidemiologic studies have reported on associations between various "inflammatory" factors and coronary heart disease (CHD). OBJECTIVE: To assess the associations of blood levels of fibrinogen, C-reactive protein (CRP), and albumin and leukocyte count with the subsequent risk of CHD. DATA SOURCES: Meta-analyses of any long-term prospective studies of CHD published before 1998 on any of these 4 factors. Studies were identified by MEDLINE searches, scanning of relevant reference lists, hand searching of cardiology, epidemiology, and other relevant journals, and discussions with authors of relevant reports. STUDY SELECTION: All relevant studies identified were included. DATA EXTRACTION: The following information was abstracted from published reports (supplemented, in several cases, by the authors): size and type of cohort, mean age, mean duration of follow-up, assay methods, degree of adjustment for confounders, and relationship of CHD risk to the baseline assay results. DATA SYNTHESIS: For fibrinogen, with 4018 CHD cases in 18 studies, comparison of individuals in the top third with those in the bottom third of the baseline measurements yielded a combined risk ratio of 1.8 (95% confidence interval [CI], 1.6-2.0) associated with a difference in long-term usual mean fibrinogen levels of 2.9 pmol/L (0.1 g/dL) between the top and bottom thirds (10.3 vs 7.4 pmol/L [0.35 vs 0.25 g/dL]). For CRP, with 1053 CHD cases in 7 studies, the combined risk ratio of 1.7 (95% CI, 1.4-2.1) was associated with a difference of 1.4 mg/L (2.4 vs 1.0 mg/L). For albumin, with 3770 CHD cases in 8 studies, the combined risk ratio of 1.5 (95% CI, 1.3-1.7) was associated with a difference of 4 g/L (38 vs 42 g/L, ie, an inverse association). For leukocyte count, with 5337 CHD cases in the 7 largest studies, the combined risk ratio of 1.4 (95% CI, 1.3-1.5) was associated with a difference of 2.8 x 10(9)/L (8.4 vs 5.6 x 10(9)/L). Each of these overall results was highly significant (P<.0001). CONCLUSIONS: The published results from these prospective studies are remarkably consistent for each factor, indicating moderate but highly statistically significant associations with CHD. Hence, even though mechanisms that might account for these associations are not clear, further study of the relevance of these factors to the causation of CHD is warranted.     

Increased coronary heart disease in Japanese-American men with mutation in the cholesteryl ester transfer protein gene despite increased HDL levels

Plasma high density lipoprotein (HDL) levels are strongly genetically determined and show a general inverse relationship with coronary heart disease (CHD). The cholesteryl ester transfer protein (CETP) mediates the transfer of cholesteryl esters from HDL to other lipoproteins and is a key participant in the reverse transport of cholesterol from the periphery to the liver. A high prevalence of two different CETP gene mutations (D442G, 5.1%; intron 14G:A, 0.5%), was found in 3,469 men of Japanese ancestry in the Honolulu Heart Program and mutations were associated with decreased CETP (-35%) and increased HDL chol levels (+10% for D442G). However, the overall prevalence of definite CHD was 21% in men with mutations and 16% in men without mutations. The relative risk (RR) of CHD was 1.43 in men with mutations (P < .05); after adjustment for CHD risk factors, the RR was 1.55 (P = .02); after additional adjustment for HDL levels, the RR was 1.68 (P = .008). Similar RR values were obtained for the D442G mutation alone. Increased CHD in men with mutations was primarily observed for HDL chol 41-60 mg/dl; for HDL chol > 60 mg/dl men with and without mutations had low CHD prevalence. Thus, genetic CETP deficiency appears to be an independent risk factor for CHD, primarily due to increased CHD prevalence in men with the D442G mutation and HDL cholesterol between 41 and 60 mg/dl. The findings suggest that both HDL concentration and the dynamics of cholesterol transport through HDL (i.e., reverse cholesterol transport) determine the anti-atherogenicity of the HDL fraction.     

Epidemiology of coagulation factors, inhibitors and activation markers: The Third Glasgow MONICA Survey. II. Relationships to cardiovascular risk factors and prevalent cardiovascular disease

Coagulation factor activity (fibrinogen, VII, VIII and IX), coagulation inhibitor activity (antithrombin, protein C, protein S), and coagulation activation markers (prothrombin fragment F1, 2; thrombin-antithrombin complexes) were measured in 746 men and 816 women aged 25-74 years, randomly sampled from the north Glasgow population in the Third MONICA Survey. After age-adjustment, significant associations with cardiovascular risk factors were observed. Serum cholesterol and triglyceride were associated with increases in factors VII and IX, as well as antithrombin, protein C and protein S; and with increased fibrinogen and factor VIII in women. Apart from factor VIII (related to blood pressure in men, but not in women), similar associations were observed for blood pressure and body mass index. Smoking status and/or smoking markers were related to fibrinogen, factor IX, antithrombin and protein S. Alcohol intake was related to protein S, and inversely to fibrinogen and antithrombin in men. Low social class was associated with fibrinogen, factor VIII, factor IX, and with antithrombin, protein S, and low protein C in men. Serum vitamin C was associated inversely with coagulation factors and coagulation inhibitors. The only associations of activation markers were with low serum vitamin C, and with alcohol consumption and low social class in men. Prevalent cardiovascular disease was associated only with fibrinogen. These associations of coagulation factors and inhibitors with cardiovascular risk factors are plausibly relevant to thrombotic risk in cardiovascular disease. In general, 'worse' values of risk factors are associated with increased plasma levels of both coagulation factors and inhibitors, without significant increase in coagulation activation markers. However, the association of lower serum vitamin C with increased coagulation activation markers is of potential therapeutic interest.     

Associations between skeletal muscle properties, physical fitness, physical activity and coronary heart disease risk factors in men

High physical fitness and physical activity are associated with favourable lipid levels, especially a high level of high density lipoprotein cholesterol (HDL-C). A person's skeletal muscle properties, metabolism and percentage of different muscle fibres (ST-%), which may modify coronary heart disease (CHD) risk factors, such as serum insulin, obesity and serum sex hormones may also influence his fitness level and leisure-time physical activity. We studied the associations of physical fitness, physical activity and ST-% with serum lipids and lipoproteins in 72 healthy men. Their parameters were compared with those of 20 men with defined CHD. Significant interrelationships between ST-%, fitness and leisure-time physical activity index (LTPAI) were observed. Multiple regression analysis showed that ST-%, fitness and leisure-time physical activity explained about 32% of the variation in HDL-C in the healthy men. In healthy men ST-% correlated positively with fitness (r(s) = 0.62, P < 0.001) and with LTPAI (r(s) = 0.62, P < 0.001). Fitness level also correlated significantly with LTPAI (r(s) = 0.81, P < 0.001). Serum insulin showed negative associations with ST-% (r(s) = -0.63, P < 0.001) and fitness (r(s) = -0.54, P < 0.001) and LTPAI (r(s) = -0.62, P < 0.001). Free fraction of testosterone correlated negatively with serum HDL-C level (r(s) = -0.34, P < 0.01), with fitness (r(s) = -0.41, P < 0.001) and with LTPAI (r(s) = -0.54, P < 0.001). In sedentary men with the lowest fitness and physical activity the mean of ST-% (45%) was similar to that in CHD patients (44%). However, ST-% in men in the highest tertile of physical activity and fitness (68%) was significantly higher than in CHD patients and in men in the lowest tertile of physical activity and fitness. Skeletal muscle enzyme activity in lipid metabolism was significantly lower in both CHD patients and in sedentary and low-fit men than that in fitter and physically active men. The present data imply that skeletal muscle properties are important determinants of risk profiles, such as physical activity, fitness and serum lipid and lipoprotein patterns. Although fitness is a graded, independent predictor of mortality from CHD, a relatively high fitness level is not enough. This was clearly observed in the clustering analysis, in which the healthy men, according to their ST-%, fitness, leisure-time physical activity and serum sex hormone binding globulin (SHBG), fell into three natural groups: (i) Inactive men with lowest ST-% (mean 42%), lowest fitness (10.7 METs) and lowest HDL-C (1.36 mm/l); (ii) Fit men with high ST-% (66%), high fitness (14.5 METs) and moderately high HDL-C (1.54 mol/l); (iii) Active men with high ST-% (66%), highest fitness (14.9 METs) and highest serum HDL (1.83 mmol/l). The results support the idea that both fitness and physical activity give further protection against CHD by modifying risk factors. Our findings also suggest that skeletal muscle properties should be considered in the studies which assess CHD risk factors and their modifications especially in the field of health-related fitness.     

Psychological disorder and mortality in French older adults: do social relations modify the association?

The possible modifying effect of social relations on the association between depression and mortality was examined in a community-based cohort study. A total of 3,777 randomly selected persons 65 years of age and older in southwest France were followed over a 5-year period from 1988 in the Personnes Agees Quid (PAQUID). At study entry, the prevalence of elevated depressive symptomatology was 12.9% for men and 14.7% for women, and the reported relative isolation was 14.1% for men and 26.0% for women. During a total of 16,984 person-years of follow-up, 849 deaths occurred. Among participants with high levels of depressive symptomatology, the age-adjusted mortality rate ratio was 2.10 (95% confidence interval 1.7-2.7) in men and 1.76 (95% confidence interval 1.4-2.3) in women. When compared with individuals with the most connections, men and women with few social network connections were also at increased risk of mortality: age-adjusted rate ratio = 2.69 (95% confidence interval 1.9-3.8) for men and 1.56 (95% confidence interval 1.0-2.4) for women. Satisfaction with social support had a small but nonsignificant effect on mortality risk. For women, the excess risks due to depressive symptoms and few network connections are observed only in the 65- to 74-year age group, after adjusting for health and health behaviors. Social relations did not significantly modify the depression-mortality associations for either men or women, although the depression-mortality effect was reduced by 12.8% in men. The latter findings do not appear to be compatible with the buffering hypothesis, whereby we would expect social relations to decrease the depression-mortality association. Nonetheless, there are independent effects from these two factors, and older men who are depressed and not socially connected are at increased risk of dying earlier.     

Calcium, vitamin D, and dairy foods and the occurrence of colon cancer in men

To examine the associations between intakes of calcium, Vitamin D, and dairy foods and the risk of colon cancer, the authors analyzed data from a prospective study of 47,935 US male professionals, 40-75 years of age and free of cancer in 1986. Within this cohort, 203 new cases of colon cancer were documented between 1986 and 1992. After adjusting for age and total energy intake, the authors found that the intake of calcium from foods and supplements was inversely associated with colon cancer risk (relative risk (RR) = 0.58, 95% confidence interval (CI) 0.39-087 between high and low intakes of calcium). However, after adjusting for confounding variables, they found that the trend was no longer statistically significant (p = 0.22), and the relative risk for the highest quintile group of intake was attenuated: 0.75 (95% CI 0.48-1.15). Similar results were observed for total vitamin D intake; the age- and energy-adjusted relative risk was 0.54% (95% CI 0/34-0/85) for the highest versus lowest quintile group, and this was attenuated in the multivariate model (RR = 0.66, 95% CI 0.42-1.05). The inverse association was weaker for dietary vitamin D (RR highest vs. lowest quintile = 0.88. 95% CI 0.54-1.42) and strongest for vitamin D arising from vitamin supplements (RR = 0.48, 95% CI 0.22-1.02). Thus, it is possible that other components of multivitamin use rather than vitamin D accounted for the reduction in risk. Consumption of milk and fermented dairy products was not significantly associated with the risk of colon cancer; individuals consuming two or more glasses of "whole" or skim milk per day had a relative risk of 1.09 (95% CI 0.69-1.72), compared with those who consumed "whole or skim milk less than once a month. These prospective data do not support the hypothesis that calcium intake is strongly protective against colon cancer risk, although a modest association cannot be excluded.