Effects of levodopa on cognitive functioning in moderate-to-severe Parkinson's disease (MSPD).

Although improved cognition has been reported in patients with mild Parkinson's disease (PD) following the administration of levodopa, mixed results have been found in moderately-to-severely affected PD patients (MSPD), particularly in studies conducted since 1980. In the present study, 16 MSPD patients were tested on separate days, once following overnight levodopa withdrawal and once while optimally treated. A battery of neuropsychological tests that assess a range of cognitive functions (i.e., attention, language, visuospatial, memory, and executive), as well as a measure of depression, were used. Although patients performed better on a measure of confrontation naming in the untreated than in the treated condition, there were no significant differences for any of the other cognitive variables or for the depression scale variable. Thus, these data suggest that there are generally no adverse or beneficial effects of levodopa therapy on cognition in MSPD patients.

Neuropsychological functioning following bilateral subthalamic nucleus stimulation in Parkinson's disease.

The cognitive effects of subthalamic nucleus (STN) stimulation in Parkinson's disease (PD) have been examined. However, there are no reported studies that evaluate, by incorporating a disease control group, whether neuropsychological performance in surgical patients changes beyond the variability of the assessment measures. To examine this issue, 17 PD patients were tested before and after bilateral STN stimulator implantation, both on and off stimulation. Eleven matched PD controls were administered the same repeatable neuropsychological test battery twice. Relative to changes seen in the controls, the surgery for electrode placement mildly adversely affected attention and language functions. STN stimulation, per se, had little effect on cognition. The STN DBS procedure as a whole resulted in a mild decline in delayed verbal recall and language functions. There were no surgery, stimulation, or procedure effects on depression scale scores. In contrast to these group findings, one DBS patient demonstrated significant cognitive decline following surgery.

Associations of plasma fibrinogen assays, C-reactive protein and interleukin-6 with previous myocardial infarction.

BACKGROUND: The association of plasma fibrinogen with myocardial infarction (MI) may (like that of C-reactive protein, CRP) be a marker of subclinical inflammation, mediated by cytokines such as interleukin-6 (IL-6). There are well-recognized discrepancies between commonly performed fibrinogen assays. Increased ratio of clottable fibrinogen to intact fibrinogen (measured by a recently developed immunoassay) has been proposed as a measure of hyperfunctional fibrinogen, and is elevated in acute MI. OBJECTIVE: To compare the associations of intact fibrinogen and four routine fibrinogen assays (two von Clauss assays; one prothrombin-time derived; and one immunonephelometric) in a case-control study of previous MI. PATIENTS/METHODS: Cases (n=399) were recruited 3-9 months after their event; 413 controls were age- and sex- matched from the case-control study local population. Intact fibrinogen was measured in 50% of subjects. RESULTS: All routine fibrinogen assays showed high intercorrelations (r=0.82-0.93) and significant (P<0.0001) increased mean levels in cases vs. controls. These four routine assays correlated only moderately with intact fibrinogen (r=0.45-0.62), while intact fibrinogen showed only a small, nonsignificant increase in cases vs. controls. Consequently, the ratio of each of the four routine assays to the intact fibrinogen assay was significantly higher (P<0.0003) in cases vs. controls. Each fibrinogen assay correlated with plasma levels of CRP and IL-6 (which were also elevated in cases vs. controls). Each routine fibrinogen assay remained significantly elevated in cases vs. controls after further adjustment for C-reactive protein and interleukin-6. CONCLUSIONS: These data provide evidence for acquired, increased hyperfunctional plasma fibrinogen in MI survivors, which is not associated with markers of inflammatory reactions. The causes and significance of these results remain to be established in prospective studies.

Phenotypic features of myoclonus-dystonia in three kindreds.

BACKGROUND: Myoclonus-dystonia (M-D) is a movement disorder with involuntary jerks and dystonic contractions. Autosomal dominant alcohol-responsive M-D is associated with mutations in the epsilon-sarcoglycan gene (SGCE) (six families) and with a missense change in the D2 dopamine receptor (DRD2)gene (one family). OBJECTIVE: To investigate the clinical phenotype associated with M-D including motor symptoms, psychiatric disorders, and neuropsychological deficits. METHODS: Fifty individuals in three M-D families were evaluated and a standardized neurologic examination and DNA analysis were performed. Psychiatric profiles were established with the Diagnostic Interviews for Genetic Studies (DIGS) and the Yale-Brown Obsessive-Compulsive Scale (YBOCS). Cognition was evaluated with standardized neuropsychological tests. RESULTS: Distinct truncating mutations in the SGCE gene were identified in each family. Additionally, a missense alteration in the DRD2 gene was previously found in one family. Motor expression was variable, with onset of myoclonus or dystonia or both affecting the upper body and progression to myoclonus and dystonia in most cases. Psychiatric profiles revealed depression, obsessive-compulsive disorder, substance abuse, anxiety/panic/phobic disorders, and psychosis in two families, and depression only in the third family. Averaged scores from cognitive testing showed impaired verbal learning and memory in one family, impaired memory in the second family, and no cognitive deficits in the third family. CONCLUSIONS: Cognitive deficits may be associated with M-D. Psychiatric abnormalities correlate with the motor symptoms in affected individuals. Assessment of additional M-D families with known mutations is needed to determine whether these are characteristic phenotypic manifestations of M-D.

Randomised controlled trial of specialist nurse intervention in heart failure.

OBJECTIVES: To determine whether specialist nurse intervention improves outcome in patients with chronic heart failure. DESIGN: Randomised controlled trial. SETTING: Acute medical admissions unit in a teaching hospital. PARTICIPANTS: 165 patients admitted with heart failure due to left ventricular systolic dysfunction. The intervention started before discharge and continued thereafter with home visits for up to 1 year. MAIN OUTCOME MEASURES: Time to first event analysis of death from all causes or readmission to hospital with worsening heart failure. RESULTS: 31 patients (37%) in the intervention group died or were readmitted with heart failure compared with 45 (53%) in the usual care group (hazard ratio=0.61, 95% confidence interval 0.33 to 0.96). Compared with usual care, patients in the intervention group had fewer readmissions for any reason (86 v 114, P=0.018), fewer admissions for heart failure (19 v 45, P<0.001) and spent fewer days in hospital for heart failure (mean 3.43 v 7.46 days, P=0.0051). CONCLUSIONS: Specially trained nurses can improve the outcome of patients admitted to hospital with heart failure.

Left ventricular dysfunction, natriuretic peptides, and mortality in an urban population.

OBJECTIVE: To report the mortality of left ventricular systolic dysfunction (LVD), assessed objectively by echocardiography, and its association with natriuretic peptide hormones in a random sample of 1640 men and women aged 25-74 years from a geographical, urban population. METHODS: Left ventricular function was measured by echocardiography in 1640 attendees studied in 1992-3. LVD was defined as a left ventricular ejection fraction (LVEF) 30% (p < 0.001). The median (interquartile range) BNP concentration in those who died was 16.9 pg/ml (8.8-27) and 7.8 pg/ml (3.4-13) in survivors (p < 0.0001). Similarly, N-ANP had a median concentration of 2.35 ng/ml (1.32-3.36) in those with a fatal outcome and 1.27 ng/ml (0.9-2.0) in those alive at four years (p < 0.0001). Subjects with an LVEF /= 17.9 pg/ml compared with 6.8% if their BNP was below this concentration (p = 0.013). Multivariate analysis revealed the independent predictors of four year all cause mortality to be increasing age (p < 0.001), a BNP concentration >/= 17.9 pg/ml (p = 0.006), the presence of ischaemic heart disease (p = 0.03), and male sex (p = 0.04). CONCLUSIONS: LVD is associated with a considerable mortality rate in this population. BNP also independently predicts outcome. In addition to its role as a diagnostic aid in chronic heart failure and LVD, it provides prognostic information and clarifies the meaning of a given degree of LVD.

Delay in calling for help during myocardial infarction: reasons for the delay and subsequent pattern of accessing care.

OBJECTIVE: To determine the reasons for delay in calling for help during acute myocardial infarction and the reasons for choice of first medical contact. DESIGN: Review of routine medical records and one to one semi-structured interviews. SETTING: Community survey in city of Glasgow, north of the river Clyde. PATIENTS: 228 men and 85 women aged between 25 and 65 years, respectively, who survived acute myocardial infarction between October 1994 and December 1996. RESULTS: Only 25% of the subjects made a call for help within one hour of the onset of coronary symptoms; in 40% the delay was greater than four hours. Symptoms were not recognised as coronary in origin in the majority of cases. In all cases where delay was more than one hour the main reasons for the delay were thinking that symptoms would go away or that they were not serious. Requesting the attendance of a general practitioner was the first course of action in the majority of cases (55%); the main reason given was that the patient believed this should always be the first course of action. Reluctance to call the emergency services reflected the belief that the symptoms were not serious enough to warrant an ambulance. CONCLUSIONS: Strategies to reduce patient delay times in this deprived urban population must focus on educating the public on the recognition and diversity of coronary symptoms and the benefits of presenting promptly to hospital by way of the emergency ambulance service.

A program for neuropsychological investigation of deep brain stimulation (PNIDBS) in movement disorder patients: development, feasibility, and preliminary data.

OBJECTIVE: This technical report and feasibility study propose a standardized method for collecting neuropsychological data in patients undergoing the deep brain stimulation (DBS) procedure. BACKGROUND: Programs for standardizing motor data collected in studies investigating surgical therapies for Parkinson disease are already widely used (e.g., Core Assessment Program for Intracerebral Transplantations). The development and rationale for the proposed Program for Neuropsychological Investigation of Deep Brain Stimulation (PNIDBS) are outlined, and support for the feasibility of these methodologies is provided via preliminary data. METHOD: The PNIDBS includes a core battery of neuropsychological tests that assesses a wide range of cognitive functions (attention, language, visuospatial, memory, and executive) as well as depression. Using the PNIDBS, three Parkinson disease and two dystonia patients were evaluated at baseline and after surgery, once with stimulation off and once with stimulation on. RESULTS: Patients with severe motor disabilities were able to complete the PNIDBS. These preliminary data suggest that the DBS procedure as a whole had a minimal impact on cognitive functioning in most patients studied. There was also some evidence that the one patient who showed cognitive decline after the DBS procedure had demographic and clinical characteristics that may have put him at risk for this decline. CONCLUSIONS: The procedures in the PNIDBS were systematically developed and are feasible to execute. The relatively brief core battery has multiple versions and can be supplemented to meet individual investigator needs. By evaluating the components of the DBS procedure (electrode placement and stimulation), the PNIDBS can address clinical questions regarding the cognitive effects of the DBS procedure as well as investigate basic scientific issues regarding how different cognitive functions are affected when subcortical-prefrontal circuits are manipulated by the DBS procedure.

Measuring the costs and benefits of heart disease monitoring.

OBJECTIVE: To evaluate the costs and benefits of alternative systems of coronary heart disease monitoring in Scotland. DESIGN: An option appraisal was conducted to evaluate the costs and benefits of implementing a coronary heart disease monitoring system. This involved a review of existing Scottish datasets and relevant reports, specification of options, definition and weighting of benefit criteria by key stakeholders, assessment of options by experts, and costing of options. The options were assessed by 33 stakeholders (grouped as cardiologists, patient representatives, general practitioners, public health physicians, and policy makers), plus 13 topic experts. SETTING: Scotland (population 5.1 million). RESULTS: Between group mean benefit weights were: mortality rates and case fatality (10.6), quality of life (9.8), patient function (8.8), hospital activity (7.8), primary care activity (9.25), prescribing (5.72), socioeconomic impact (4.0), risk factors (7.4), prevalence (5.0), incidence (6.0), case registration (6.82), international comparability (4.2), breadth of coverage (8.8), and frequency (5.8). Differences between group weights were significant for prevalence (p = 0.048) and international comparability (p = 0.032). Four monitoring options were identified: a community epidemiology model, based on MONICA (monitoring trends and determinants in cardiovascular disease) study methodology applied to a series of eight representative communities, had the highest benefits, at an average annual discounted cost of approximately pound 360,000; models based on the Australian cardiovascular disease monitoring scheme and on enhanced routine data offered fewer benefits at discounted average annual costs ranging from pound 165,000 to pound 195,000; finally, a coronary heart disease registry modelled on the Scottish Cancer Registry scheme would have had fewer benefits and substantially higher costs than the other options. CONCLUSIONS: The most beneficial coronary heart disease monitoring system is the community epidemiology model, based on MONICA methodology. Option appraisal potentially offers an explicit and transparent methodology for evidence based policy development.

The prevalence of dyspepsia and use of antisecretory medication in North Glasgow: role of Helicobacter pylori vs. lifestyle factors.

AIMS: To determine the prevalence of dyspepsia and associated antisecretory medication usage, and their associations with H. pylori infection in the general population. In addition, to compare the importance of H. pylori infection relative to other potential causes of dyspepsia: alcohol, smoking and obesity. METHODS: The study examined a random population sample of 784 men and 827 women from Glasgow. They completed a validated dyspepsia questionnaire and had their H. pylori status determined by serology. RESULTS: The overall prevalence of dyspepsia was 12%; prescribed antisecretory medication had been used over the last 6 months by 7%. The odds ratio (95% CI) for dyspepsia, comparing H. pylori-positives to negatives was 1.79 (1.03, 3.09) for men and 1.11 (0.70, 1.78) for women. Ever-smoking (both sexes) and obesity (women) had higher odds ratios for dyspepsia than did H. pylori. Adjustment for age, social class, ever-smoking, ever-drinking and obesity reduced the H. pylori odds ratios for dyspepsia to 1.38 (0.73, 2.60) for men and 0.99 (0. 57, 1.73) for women. The association between H. pylori and antisecretory medication usage was similar to that for dyspepsia. CONCLUSION: Obesity and smoking are more important risk factors, for dyspepsia and antisecretory medication usage, than is H. pylori. Reducing the burden and cost of dyspepsia will require lifestyle modification and not merely H. pylori eradication.

Age and health indications assessed by silhouette photographs.

OBJECTIVE: To test the hypothesis that overweight and central fat distribution make people look older and have poorer health. DESIGN: We asked 201 male and 161 female observers aged 28-67 y with body mass index (BMI) 17-45 kg/m2, to estimate the age of eight silhouette photographs of female volunteers with known BMI and waist and hips. Silhouette photographs were presented individually and grouped in three trios for analysis: trio A, each subject had waist to hip ratio = 0.7, BMI for each subject was 22, 24, 29 kg/m2; trio B, each subject had BMI = 22 kg/m2, waist to hip ratio for each subject was 0.66, 0.73, 0.99; and trio C, each subject had BMI = 29 kg/m2, waist to hip ratio for each subject was 0.76, 0.88, 0.99. The observers were then asked to judge the likelihood of developing heart disease, health and longevity of the silhouettes which were presented in four pairs controlling either for BMI or waist to hip ratio. RESULTS: The age of a silhouette with BMI 22 kg/m2 was estimated to be 35 y, 24 kg/m2 to be 45 y, and 30 kg/m2 to be 55 y, when waist to hip ratio was matched at 0.7. When BMI was controlled at either 22 or 29 kg/m2, higher waist to hip ratio led to a greater age estimation. An increase from a 65 cm to 88 cm waist circumference led to an estimate of 25 y older. Narrow hips was also judged as older. The silhouettes judged the more likely to be healthy and live longer were those with the lower waist to hip ratio (by 70% observers), and the lower BMI (by 90% observers). Waist to hip ratio appeared less influential when BMI of the silhouettes was high. The observers' own BMI, age or sex had little influences on their assessments of the age and health status of the silhouette photographs. CONCLUSIONS: Using novel sets of silhouette photographs, it was shown that overweight or central fat distribution and narrow hips suggest a person is older and has poorer health: People with BMI 29.7 kg/m2 appear to be 15-18 y older than those with BMI 22.2 kg/m2, each extra cm on the waist makes women appear to look a year older, and progressively less healthy. BMI and age of the observers had little influences on the findings.

Prescribing and emergency admissions for heart failure in greater Glasgow.

BACKGROUND: We sought to determine whether there is an association between the rate of prescription of angiotensin-converting enzyme (ACE) inhibitors and the rate of hospitalization for heart failure. METHODS AND RESULTS: We conducted a cross-sectional study linking prescribing data with hospital admission data from 215 primary health care practices in Greater Glasgow, United Kingdom. We obtained numbers of prescriptions of diuretics. ACE inhibitors, and digoxin and numbers of admissions for heart failure. The mean practice rate of diuretic prescription was 0.7 per patient per year, the mean practice rate of ACE inhibitor prescription was 0.06 per patient per year, the mean practice rate of digoxin prescription was 0.09 per patient per year, and the mean practice rate of admission for heart failure was 3.29 per 1,000 patients per year. There was a strong and significant association between the rate of diuretic prescription and the rate of digoxin prescription. There was only a moderate inverse association between the ratio of ACE inhibitor to diuretic prescriptions and the rate of admissions for heart failure. CONCLUSIONS: ACE inhibitors are underused. Rates of diuretic and digoxin prescriptions correlate strongly and are presumably both markers for similar cardiovascular morbidity. There was no evidence that ACE inhibitors modulated the rate of heart failure admissions.

Contribution of modern cardiovascular treatment and risk factor changes to the decline in coronary heart disease mortality in Scotland between 1975 and 1994.

OBJECTIVE: To estimate the fall in coronary heart disease (CHD) mortality in Scotland attributable to medical and surgical treatments, and risk factor changes, between 1975 and 1994. DESIGN: A cohort model combining effectiveness data from meta-analyses with information on treatment uptake in all patient categories in Scotland. SETTING AND PATIENTS: The whole Scottish population of 5.1 million, including all patients with recognised CHD. INTERVENTIONS: All cardiological, medical, and surgical treatments, and all risk factor changes between 1975 and 1994. Data were obtained from epidemiological surveys, routine National Health Service sources, and local audits. MAIN OUTCOME MEASURES: Deaths from CHD in 1975 and 1994. RESULTS: There were 15 234 deaths from CHD in 1994, 6205 fewer deaths than expected if there had been no decline from 1975 mortality rates. In 1994, the total number of deaths prevented or postponed by all treatments and risk factor reductions was estimated at 6747 (minimum 4790, maximum 10 695). Forty per cent of this benefit was attributed to treatments (initial treatments for acute myocardial infarction 10%, treatments for hypertension 9%, for secondary prevention 8%, for heart failure 8%, aspirin for angina 2%, coronary artery bypass grafting surgery 2%, and angioplasty 0.1%). Fifty one per cent of the reduction in deaths was attributed to measurable risk factor reductions (smoking 36%, cholesterol 6%, secular fall in blood pressure 6%, and changes in deprivation 3%). Other, unquantified factors apparently accounted for the remaining 9%. These proportions remained relatively consistent across a wide range of assumptions and estimates in a sensitivity analysis. CONCLUSIONS: Medical treatments and risk factor changes apparently prevented or postponed about 6750 coronary deaths in Scotland in 1994. Modest gains from individual treatments produced a large cumulative survival benefit. Reductions in major risk factors explained about half the fall in coronary mortality, emphasising the importance and future potential of prevention strategies.

Biochemical detection of left-ventricular systolic dysfunction.

BACKGROUND: In previous studies on the use of natriuretic peptides to detect left-ventricular systolic dysfunction, a higher rate of cardiac disorders in the control groups than in the study groups could have led to bias. We investigated the effectiveness of plasma N-terminal atrial natriuretic peptide (NT-ANP) and brain natriuretic peptide (BNP) concentrations to show left-ventricular systolic dysfunction in a random sample of the general population. METHODS: We randomly selected 2000 participants aged 25-74 years from family physicians' lists in Glasgow, UK. We sent all participants questionnaires. 1653 respondents underwent echocardiography and electrocardiography. We took a left-ventricular ejection fraction of 30% or less to show left-ventricular systolic dysfunction. NT-ANP and BNP were measured in plasma by RIAs. FINDINGS: 1252 participants had analysable electrocardiograms and echocardiograms, completed questionnaires, and available blood samples. Median concentrations of NT-ANP and BNP were significantly higher in participants with left-ventricular systolic dysfunction (2.8 ng/mL [IQR 1.8-4.6] and 24.0 pg/mL [18.0-33.0]) than in those without (1.3 ng/mL [0.9-1.8] and 7.7 pg/mL [3.4-13.0]; each p < 0.001). Among participants with left-ventricular systolic dysfunction, both symptomatic and asymptomatic subgroups had raised NT-ANP and BNP concentrations. A BNP concentration of 17.9 pg/mL or more gave a sensitivity of 77% and specificity of 87% in all participants, and 92% and 72% in participants aged 55 years or older. INTERPRETATION: Measurement of BNP could be a cost-effective method of screening for left-ventricular systolic dysfunction in the general population, especially if its use were targeted to individuals at high risk.

Importance of heart failure as a cause of death. Changing contribution to overall mortality and coronary heart disease mortality in Scotland 1979-1992.

AIMS: As heart failure is a syndrome arising from another condition, such as coronary heart disease, it is rarely officially coded as the underlying cause of death regardless of the cause recorded by the physician at the time of certification. We sought to assess the true contribution of heart failure to overall mortality and coronary heart disease mortality and to examine how this contribution has changed over time. METHODS AND RESULTS: We carried out a retrospective analysis of all death certificates in Scotland between 1979 and 1992 for which heart failure was coded as the underlying or a contributory cause of death. From a total of 833622 deaths in Scotland between 1979 and 1992, heart failure was coded as the underlying cause in only 1.5% (13695), but as a contributory cause in a further 14.3% (126073). In 1979, 28.5% of male and 40.4% of female deaths attributed to coronary heart disease (coded as the underlying cause of death) also had a coding for heart failure. In 1992 these percentages had risen significantly to 34.1% and 44.8%, respectively (both P<0.001). Mortality rates for heart failure as the underlying or contributory cause of death, standardized by age and sex, fell significantly over the period studied in all ages and in both sexes: by 31% in men and 41% in women <65 years and 15.8% in men and 5.1% in women > or =65 years, respectively (P<0.01 for all changes). CONCLUSIONS: Death from heart failure is substantially underestimated by official statistics. Furthermore, one third or more of deaths currently attributed to coronary heart disease may be related to heart failure and this proportion appears to be increasing. While the absolute numbers of deaths caused by heart failure remains constant, this study is the first to show that standardized mortality rates are declining.

Symptomatic and asymptomatic left-ventricular systolic dysfunction in an urban population.

BACKGROUND: In most previous epidemiological studies on the prevalence of chronic heart failure (CHF) the disorder has been defined on clinical criteria. In a cross-sectional survey of 2000 men and women aged 25-74, randomly sampled from one geographical area, we assessed left-ventricular systolic function by echocardiography. METHODS: 1640 (83%) of those invited took part. They completed a questionnaire on current medication, history, and symptoms of breathlessness. Blood pressure was measured and electrocardiography (ECG) and echocardiography were done. Left-ventricular ejection fraction was measurable in 1467 (89.5%) participants by the biplane Simpson's rate method. FINDINGS: The mean left-ventricular ejection fraction was 47.3%. The prevalence of definite left-ventricular systolic dysfunction (defined as a left-ventricular ejection fraction < or = 30%) was 2.9% overall (43 participants); it increased with age and was higher in men than in women (4.0 vs 2.0%). The left-ventricular systolic dysfunction was symptomatic in 1.5% of participants and asymptomatic in 1.4%, 83% of participants with left-ventricular systolic dysfunction had evidence of ischaemic heart disease (IHD) from history or ECG criteria compared with 21% of those without this abnormality (p < 0.001). Hypertension was also more common in those with left-ventricular systolic dysfunction (72 vs 38%, p < 0.001), but there was no difference between those with and without left-ventricular systolic dysfunction in the rate of hypertension without IHD. INTERPRETATION: Left-ventricular systolic dysfunction was at least twice as common as symptomatic heart failure defined by clinical criteria. The main risk factors are IHD and hypertension in the presence of IHD; screening of such high-risk groups for left-ventricular systolic dysfunction should be considered.

Helicobacter pylori infection and coronary heart disease in the North Glasgow MONICA population.

AIM: Recent evidence suggests that Helicobacter pylori infection is associated with coronary heart disease. We investigated whether H. Pylori infection is related to prevalent coronary heart disease, in a random sample of 1428 men and women aged 25-74 years. METHODS AND RESULTS: Coronary heart disease was assessed by questionnaire and electrocardiography (ECG). Standard risk factors for coronary heart disease, fibrinogen concentration and serum concentrations of H. pylori-specific IgG antibody were measured. H. pylori seropositivity increased with age (P < or = 0.001) and was significantly more prevalent in men than women. H. pylori infection was associated with current smoking and a higher systolic blood pressure in men but not in women. There was no significant increase in the odds ratio in those seropositive for H. pylori with regard to any manifestation of coronary heart disease, after adjustment for age, standard cardiovascular risk factors and social class. Likewise, age-adjusted plasma fibrinogen was no higher in seropositives. CONCLUSION: Seropositivity to H. pylori is associated with a trend towards a greater prevalence of coronary heart disease. However, that association is likely to be spurious and can be adequately explained by the much stronger association of H. pylori infection with age and social class, both of which are linked with coronary heart disease.

Epidemiology of coagulation factors, inhibitors and activation markers: the Third Glasgow MONICA Survey. I. Illustrative reference ranges by age, sex and hormone use.

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 747 men and 817 women aged 25-74 years, randomly sampled from the north Glasgow population in the Third MONICA Survey. Significant effects of age, sex, menopause and hormone use were observed and specific reference ranges are presented to illustrate these effects. Significant correlations were observed between several coagulation factors and inhibitors. Increased levels of factors VII, VIII and IX and decreased levels of protein C were associated with increased coagulation activation. In general, increases in coagulation factors with age were greater than increases in coagulation inhibitors, especially in men; this imbalance may favour increased coagulation activation and hence increased thrombotic risk with age.

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.