Mild hyponatremia, hypernatremia and incident cardiovascular disease and mortality in older men: A population-based cohort study.

AIM: To examine the association between serum sodium concentration and incident major cardiovascular disease (CVD) outcomes and total mortality in older men. METHODS AND RESULTS: A prospective study of 3099 men aged 60-79 years without a history of cardiovascular disease followed up for an average 11 years during which there were 528 major CVD events (fatal coronary heart disease [CHD] and non-fatal MI, stroke and CVD death) and 873 total deaths. A U shaped relationship was seen between serum sodium concentration and major CVD events and mortality. Hyponatremia (<136 mEq/L) and low sodium within the normal range (136-138 mEq/L) showed significantly increased risk of major CVD events and total mortality compared to men within the upper normal range (139-143 mEq/L) after adjustment for a wide range of confounders and traditional risk factors [adjusted HRs 1.55 (1.13,2.12) and 1.40 (1.14,1.72) for major CVD events respectively and 1.30 (1.02,1.66) and 1.30 (1.11,1.53) respectively for total mortality]. Hyponatremia was associated with inflammation, NT-proBNP, low muscle mass and alkaline phosphatase; these factors contributed to the increased total mortality associated with hyponatremia but did not explain the increased risk of CVD events associated with hyponatremia or low normal sodium concentration. Hypernatremia (≥145 mEq/L) was associated with significantly increased risk of CVD events and mortality due to CVD causes. CONCLUSION: Mild hyponatremia even within the normal sodium range and hypernatremia are both associated with increased total mortality and major CVD events in older men without CVD which is not explained by known adverse CV risk factors.

Socio-demographic characteristics, lifestyle factors and burden of morbidity associated with self-reported hearing and vision impairments in older British community-dwelling men: a cross-sectional study.

BACKGROUND: Hearing and vision problems are common in older adults. We investigated the association of self-reported sensory impairment with lifestyle factors, chronic conditions, physical functioning, quality of life and social interaction. METHODS: A population-based cross-sectional study of participants of the British Regional Heart Study aged 63-85 years. RESULTS: A total of 3981 men (82% response rate) provided data. Twenty-seven per cent (n = 1074) reported hearing impairment including being able to hear with aid (n = 482), being unable to hear (no aid) (n = 424) and being unable to hear despite aid (n = 168). Three per cent (n = 124) reported vision impairment. Not being able to hear, irrespective of use of hearing aid, was associated with poor quality of life, poor social interaction and poor physical functioning. Men who could not hear despite hearing aid were more likely to report coronary heart disease (CHD) [age-adjusted odds ratios (ORs) 1.89 (95% confidence interval 1.36-2.63)]. Vision impairment was associated with symptoms of CHD including breathlessness [OR 2.06 (1.38-3.06)] and chest pain [OR 1.58 (1.07-2.35)]. Vision impairment was also associated with poor quality of life, poor social interaction and poor physical functioning. CONCLUSIONS: Sensory impairment is associated with poor physical functioning, poor health and poor social interaction in older men. Further research is warranted on pathways underlying these associations.

Neighborhood Deprivation and Changes in Oral Health in Older Age: A Longitudinal Population-Based Study.

The aim of this study was to examine the extent to which neighborhood-level socioeconomic factors (objective and perceived) are associated with poor oral health in older adults over time, independent of individual socioeconomic position. Data for this cross-sectional and longitudinal observation study came from a socially and geographically representative cohort of men aged 71 to 92 y in 2010-12 (n = 1,622), drawn from British general practices, which was followed up in 2018-19 (aged 78-98 y; N = 667). Dental measures at both times included number of teeth, periodontal pocket depth, self-rated oral health, and dry mouth. Neighborhood deprivation was based on Index of Multiple Deprivation (IMD) and a cumulative index measuring perceptions about local environment. Individual-level socioeconomic position was based on longest-held occupation. Multilevel and multivariate logistic regressions, adjusted for relevant sociodemographic, behavioral, and health-related factors, were performed to examine the relationships of dental measures with IMD and perceived neighborhood quality index, respectively. Cross-sectionally, risks of tooth loss, periodontal pockets, and dry mouth increased from IMD quintiles 1 to 5 (least to most deprived); odds ratios (ORs) for quintile 5 were 2.22 (95% confidence interval [CI], 1.41-3.51), 2.82 (95% CI, 1.72-4.64), and 1.51 (95% CI, 1.08-2.09), respectively, after adjusting for sociodemographic, behavioral, and health-related factors. Risks of increased pocket depth and dry mouth were significantly greater in quintile 5 (highest problems) of perceived neighborhood quality index compared to quintile 1. Over the 8-y follow-up, deterioration of dentition (tooth loss) was significantly higher in the most deprived IMD quintiles after full adjustment (OR for quintile 5 = 2.32; 95% CI, 1.09-4.89). Deterioration of dentition and dry mouth were significantly greater in quintile 5 of perceived neighborhood quality index. Neighborhood-level factors were associated with poor oral health in older age, both cross-sectionally and longitudinally, particularly with tooth loss, and dry mouth, independent of individual-level socioeconomic position.

The Relationships of Dentition, Use of Dental Prothesis and Oral Health Problems with Frailty, Disability and Diet Quality: Results from Population-Based Studies of Older Adults from the UK and USA.

OBJECTIVES: This study examined the relationships of dental status, use and types of dental prothesis and oral health problems, individually and combined, with diet quality, frailty and disability in two population-based studies of older adults. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: Men form the British Regional Heart Study (BRHS) (aged 85±4 years in 2018; n=1013) and Men and Women from the Health, Aging, and Body Composition (HABC) Study (aged 75±3 years in 1998-99; n=1975). MEASUREMENTS: Physical and dental examinations and questionnaires were collected with data available for dental status, oral problems related to eating, diet quality, Fried frailty phenotype, disability based on mobility limitations, and activities of daily living (ADL). The associations of dental status and oral health problems, individually and combined, with risk of frailty and disability were quantified. The relationship with diet quality was also assessed. RESULTS: In the BRHS, but not HABC Study, impaired natural dentition without the use of dentures was associated with frailty independently. This relationship was only established in the same group in those with oral problems (OR=3.24; 95% CI: 1.30-8.03). In the HABC Study, functional dentition with oral health problems was associated with greater risk of frailty (OR=2.21; 95% CI: 1.18-4.15). In both studies those who wore a full or partial denture in one or more jaw who reported oral problems were more likely to have disability. There was no association with diet quality in these groups. CONCLUSION: Older adults with impaired dentition even who use dentures who experience self-report oral problems related to eating may be at increased risk of frailty and disability. Further research is needed to establish whether improving oral problems could potentially reduce the occurrence of frailty and disability.

Are social inequalities in mortality in Britain narrowing? Time trends from 1978 to 2005 in a population-based study of older men.

OBJECTIVE: To examine whether social inequalities in all-cause and coronary heart disease (CHD) mortality in Britain have reduced between 1978 and 2005. DESIGN: A prospective study of a socioeconomically representative population. SETTING: 24 British towns. PARTICIPANTS: 7735 Men, aged 40-59 years at recruitment in 1978-1980 and followed up until 2005 through the National Health Service Central Register (164 120 person-years). MAIN OUTCOME MEASURES: Relative hazards and absolute risk differences for all-cause and CHD death comparing manual with non-manual social classes, calculated for different calendar periods. RESULTS: 3009 Deaths from all causes (1003 from CHD) occurred during follow-up. The overall hazard ratio (manual versus non-manual) was 1.56 (95% CI 1.45 to 1.69, p<0.001) for all-cause mortality and 1.54 (95% CI 1.35 to 1.76, p<0.001) for CHD mortality. The relative difference between these social groups tended to increase over time. The overall relative increase in hazard ratio comparing manual with non-manual groups over a 20-year calendar period was 1.22 (95% CI 0.83 to 1.80, p = 0.31) for all-cause mortality and 1.75 (95% CI 0.89 to 3.45, p = 0.11) for CHD mortality. The absolute difference in probability of survival to age 65 years between non-manual and manual groups fell from 29% in 1981 to 19% in 2001 for all-cause mortality and from 17% to 7% for CHD mortality. CONCLUSION: Relative differences in all-cause and CHD mortality between manual and non-manual social class groups persisted and may have increased during this period. Absolute differences in mortality between these social groups decreased as a result of falling overall mortality rates. Greater effort is needed to reduce social inequalities in all-cause and CHD mortality in the new millennium.

Effects of older age on fibrin D-dimer, C-reactive protein, and other hemostatic and inflammatory variables in men aged 60-79 years.

BACKGROUND: Previous studies have suggested that several hemostatic and inflammatory variables, which are risk predictors for arterial or venous thrombosis, increase with age. However, there is a lack of data from large population studies for reliable estimates of reference ranges. OBJECTIVES: To establish reliable reference ranges of hemostatic and inflammatory variables for 5-year age groups in older men and their implications for pathogenesis and diagnosis. PATIENTS AND METHODS: A total of 3861 men aged 60-79 years at the 20 years follow-up of the British Regional Heart Study. RESULTS: Several variables increased with age. The greatest median increases between 60-64 and 75-79 years age groups were observed for fibrin D-dimer (91%) and C-reactive protein (CRP) (57%). Significant median increases were also observed for von Willebrand factor antigen (23%), tissue plasminogen activator antigen (11%), factor VIII (10%), and fibrinogen (8%). In contrast, levels of classical cardiovascular risk factors neither decreased nor increased substantially with age, with the exception of systolic blood pressure (median increase 10%). CONCLUSIONS: The exponential increases in risk of arterial and venous thrombotic events in men between age 60 and 79 years (when most such events occur) may be related in part to increasing activation of blood coagulation, fibrinolysis, and inflammation; possibly related to the increasing inflammatory burden of both atherosclerotic and non-vascular disease. These increases also have implications for diagnosis of suspected acute venous thromboembolism (D-dimer), and recently proposed screening for prediction of coronary heart disease risk and detection of occult disease (CRP).

Prospective study of potentially virulent strains of Helicobacter pylori and coronary heart disease in middle-aged men.

BACKGROUND: Studies are needed to test claims that potentially virulent strains of Helicobacter pylori are more strongly related to coronary heart disease (CHD) than are other strains. METHODS AND RESULTS: We measured serum IgG antibodies to mixed H pylori antigens and separately to the virulence-associated H pylori antigen CagA (cytotoxin-associated gene product A) in 505 CHD cases and in 1025 age-matched controls "nested" in a prospective study of 7735 British men (mean duration of follow-up in controls, 16 years). Of the 505 cases, 401 (79%) were seropositive for H pylori antibodies compared with 740 (72%) of the 1025 controls, yielding an odds ratio for CHD of 1.55 (95% CI 1.19 to 2.03), which fell to 1.30 (95% CI 0.88 to 1. 90) after adjustments were made for standard vascular risk factors and indicators of socioeconomic status. Of the CHD cases, 240 (48%) were seropositive for IgG antibodies to CagA compared with 450 (44%) of the controls. When CagA-seropositive individuals were compared with H pylori-seronegative individuals, the odds ratio for CHD was 1. 42 (95% CI 1.06 to 1.91), which fell to 1.10 (95% CI 0.71 to 1.71) after adjustments. In an analysis restricted to the 1141 (75%) H pylori-seropositive participants, the odds ratio for CHD was 1.0 (95% CI 0.78 to 1.29) in CagA-seropositive men. No strong associations were observed between H pylori seropositivity and blood lipids, blood pressure, markers of systemic inflammation, or plasma homocysteine. CONCLUSIONS: H pylori infection is not strongly related to the incidence of CHD in late middle-aged men, and CagA-positive strains appear to be no more strongly related to the disease than other strains. However, further studies are required to confirm or refute the existence of any moderate associations, particularly at younger ages.

Fibrin D-dimer and coronary heart disease: prospective study and meta-analysis.

BACKGROUND: It is unknown whether modest increases of fibrin D-dimer, a circulating marker of fibrin turnover, are relevant to coronary heart disease (CHD) in the general population. METHODS AND RESULTS: We measured serum concentrations of D-dimer antigen in the stored baseline blood samples of 630 CHD cases and 1269 controls "nested" in a prospective cohort of 5661 men who were monitored for 16 years, and we conducted a meta-analysis of previous relevant studies to place our findings in context. In a comparison of men in the top third compared with those in the bottom third of baseline fibrin D-dimer values (tertile cutoffs, >94 versus <49 ng/mL), the odds ratio for CHD was 1.67 (95% CI, 1.31 to 2.13; P<0.0001) after adjustments for age and town. The odds ratio increased slightly after further adjustment for smoking, other classic risk factors, and indicators of socioeconomic status (1.79; 95% CI, 1.36 to 2.36). Strong correlations were observed of fibrin D-dimer values with circulating concentrations of C-reactive protein and serum amyloid A protein but not with smoking, blood lipids, blood pressure, and other risk factors. CONCLUSION: Although there may be an association between circulating D-dimer values and CHD, further studies are needed to determine the extent to which this is causal.

Burden of poor oral health in older age: findings from a population-based study of older British men.

OBJECTIVES: Evidence of the extent of poor oral health in the older UK adult population is limited. We describe the prevalence of oral health conditions, using objective clinical and subjective measures, in a population-based study of older men. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: A representative sample of men aged 71-92 years in 2010-2012 from the British Regional Heart Study, initially recruited in 1978-1980 from general practices across Britain. Physical examination among 1660 men included the number of teeth, and periodontal disease in index teeth in each sextant (loss of attachment, periodontal pocket, gingival bleeding). Postal questionnaires (completed by 2147 men including all participants who were clinically examined) included self-rated oral health, oral impacts on daily life and current perception of dry mouth experience. RESULTS: Among 1660 men clinically examined, 338 (20%) were edentulous and a further 728 (43%) had <21 teeth. For periodontal disease, 233 (19%) had loss of attachment (>5.5 mm) affecting 1-20% of sites while 303 (24%) had >20% sites affected. The prevalence of gingival bleeding was 16%. Among 2147 men who returned postal questionnaires, 35% reported fair/poor oral health; 11% reported difficulty eating due to oral health problems. 31% reported 1-2 symptoms of dry mouth and 20% reported 3-5 symptoms of dry mouth. The prevalence of edentulism, loss of attachment, or fair/poor self-rated oral health was greater in those from manual social class. CONCLUSIONS: These findings highlight the high burden of poor oral health in older British men. This was reflected in both the objective clinical and subjective measures of oral health conditions. The determinants of these oral health problems in older populations merit further research to reduce the burden and consequences of poor oral health in older people.

Cardiovascular risk profile and frailty in a population-based study of older British men.

BACKGROUND: Frailty in older age is known to be associated with cardiovascular disease (CVD) risk. However, the extent to which frailty is associated with the CVD risk profile has been little studied. Our aim was to examine the associations of a range of cardiovascular risk factors with frailty and to assess whether these are independent of established CVD. METHODS: Cross-sectional study of a socially representative sample of 1622 surviving men aged 71-92 examined in 2010-2012 across 24 British towns, from a prospective study initiated in 1978-1980. Frailty was defined using the Fried phenotype, including weight loss, grip strength, exhaustion, slowness and low physical activity. RESULTS: Among 1622 men, 303 (19%) were frail and 876 (54%) were pre-frail. Compared with non-frail, those with frailty had a higher odds of obesity (OR 2.03, 95% CI 1.38 to 2.99), high waist circumference (OR 2.30, 95% CI 1.67 to 3.17), low high-density lipoprotein-cholesterol (HDL-C) (OR 2.28, 95% CI 1.47 to 3.54) and hypertension (OR 1.79, 95% CI 1.27 to 2.54). Prevalence of these factors was also higher in those with frailty (prevalence in frail vs non-frail groups was 46% vs 31% for high waist circumference, 20% vs 11% for low HDL and 78% vs 65% for hypertension). Frail individuals had a worse cardiovascular risk profile with an increased risk of high heart rate, poor lung function (forced expiratory volume in 1 s (FEV1)), raised white cell count (WCC), poor renal function (low estimated glomerular filtration rate), low alanine transaminase and low serum sodium. Some risk factors (HDL-C, hypertension, WCC, FEV1, renal function and albumin) were also associated with being pre-frail. These associations remained when men with prevalent CVD were excluded. CONCLUSIONS: Frailty was associated with increased risk of a range of cardiovascular factors (including obesity, HDL-C, hypertension, heart rate, lung function, renal function) in older people; these associations were independent of established CVD.

The effect of the C677T and A1298C polymorphisms in the methylenetetrahydrofolate reductase gene on homocysteine levels in elderly men and women from the British regional heart study.

Total blood levels of homocysteine (tHcy) have been shown to depend on both environmental and genetic factors, and to be associated with the risk of developing atherosclerosis with its complications of coronary heart disease (CHD) and stroke. In this study, 408 men and 346 women from two towns, Dewsbury and Maidstone were examined for tHcy levels and genotyped for the C677T and the A1298C polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene. Blood tHcy was significantly higher in men from the CHD high risk town of Dewsbury (12.7 micromol/l) than in the low CHD risk town of Maidstone (11.5 micromol/l) P<0.001, but not in women (10.7 vs. 10.5 micromol/l), with women in both towns, thus, showing significantly lower tHcy than men. There was no difference between towns in folate or vitamin B12 levels but the conventional inverse relationship with tHcy was seen. Smoking men and women from both towns had significantly higher tHcy and lower folate levels than non-smoking individuals (P<0.001). The frequency of the 677T allele in Dewsbury was 0.35 (95% CI; 0.32-0.39) compared with 0.29 (95% CI; 0.26-0.32) in Maidstone (P<0.01). Similar frequency difference of borderline statistical significance was seen both for men (P=0.054) and women (P=0.048) in both the towns, suggesting a true regional frequency difference. The effect of the 677T on tHcy was highly significant in the group as a whole with the most profound effect seen in men (12.0 micromol/l for CC vs. 14.1 micromol/l for TT, P<0.001). By contrast, there was no significant effect of the A1298C polymorphism on tHcy, folate or vitamin B12 levels, with no evidence for an interaction with the C677T genotype. The regional differences in tHcy levels were still present after the adjustment for folate and vitamin B12 levels, smoking and the effect of the C677T polymorphism. This suggests that there may be other unidentified factors, either environmental or genetic, affecting tHcy levels, and thus potentially having an impact on the risk of developing hyperhomocysteinaemia and CHD. These observations may have a bearing on regional differences in tHcy levels and the variation in CHD risk between regions in the UK.

Validity of a self-reported history of doctor-diagnosed angina.

The objective of this study was to assess the validity of a self-reported history of doctor-diagnosed angina in population-based studies in men. Subjects were 5789 men from the British Regional Heart Study who reported being without an angina diagnosis at entry (1978-1980) and were alive at the end of 1992, aged 52 to 75 years. In 1992, subjects were asked in a self-administered questionnaire if they recalled ever having had a doctor diagnosis of angina. Self-report of diagnosed angina was compared with general practice (GP) record of angina obtained from reviews of medical records from study entry to the end of 1992. Men were followed for a further 3 years from 1992 for major ischemic heart disease events. The prevalence of diagnosed angina in 1992 was 10.1% according to self-reported history and 8.9% according to GP record review. There was substantial agreement between the two sources of information: 80% of men with a GP record of angina reported their diagnosis, and 70% of men who reported an angina diagnosis had confirmation of this from the record review. When all ischemic heart disease (angina or myocardial infarction) was considered, agreement was higher. Genuine angina was likely in many of the 177 men who had self-reported angina not confirmed by the GP record review: 78 had an ischemic heart disease history (myocardial infarction or coronary revascularization) identified by the review, and 31 had a GP record of angina after 1992. Angina symptoms, nitrate use, cardiological investigation, and surgical intervention for angina compared between agreement groups showed a very consistent pattern. All these indicators of angina were most common in men with both self-report and GP record of angina, least common in men with neither self-report nor GP record of angina, but had a substantially higher prevalence in men with self-reported angina only than in those with GP-recorded angina only. After 3 years follow-up from 1992, 9.5% of men with both self-report and GP record of angina, and 11.3% of men with self-reported angina only had experienced a new major ischemic heart disease event; compared to 5.7% of men with a GP record of angina only and 2.7% of those without angina by either criteria. This pattern of risk remained similar after adjustment for age and previous myocardial infarction. These results suggest that self-reported history of a doctor diagnosis of angina is a valid measure of diagnosed angina in population-based studies in men.

Low grade inflammation and coronary heart disease: prospective study and updated meta-analyses.

OBJECTIVE: To assess associations between baseline values of four different circulating markers of inflammation and future risk of coronary heart disease, potential triggers of systemic inflammation (such as persistent infection), and other markers of inflammation. DESIGN: Nested case-control comparisons in a prospective, population based cohort. SETTING: General practices in 18 towns in Britain. PARTICIPANTS: 506 men who died from coronary heart disease or had a non-fatal myocardial infarction and 1025 men who remained free of such disease until 1996 selected from 5661 men aged 40-59 years who provided blood samples in 1978-1980. MAIN OUTCOME MEASURES: Plasma concentrations of C reactive protein, serum amyloid A protein, and serum albumin and leucocyte count. Information on fatal and non-fatal coronary heart disease was obtained from medical records and death certificates. RESULTS: Compared with men in the bottom third of baseline measurements of C reactive protein, men in the top third had an odds ratio for coronary heart disease of 2.13 (95% confidence interval 1.38 to 3.28) after age, town, smoking, vascular risk factors, and indicators of socioeconomic status were adjusted for. Similar adjusted odds ratios were 1.65 (1.07 to 2.55) for serum amyloid A protein; 1.12 (0.71 to 1.77) for leucocyte count; and 0.67 (0.43 to 1.04) for albumin. No strong associations were observed of these factors with Helicobacter pylori seropositivity, Chlamydia pneumoniae IgG titres, or plasma total homocysteine concentrations. Baseline values of the acute phase reactants were significantly associated with one another (P<0.0001), although the association between low serum albumin concentration and leucocyte count was weaker (P=0.08). CONCLUSION: In the context of results from other relevant studies these findings suggest that some inflammatory processes, unrelated to the chronic infections studied here, are likely to be involved in coronary heart disease.

Chlamydia pneumoniae IgG titres and coronary heart disease: prospective study and meta-analysis.

OBJECTIVE: To examine the association between coronary heart disease and serum markers of chronic Chlamydia pneumoniae infection. DESIGN: "Nested" case-control analysis in a prospective cohort study and an updated meta-analysis of previous relevant studies. SETTING: General practices in 18 towns in Britain. PARTICIPANTS: Of the 5661 men aged 40-59 who provided blood samples during 1978-80, 496 men who died from coronary heart disease or had non-fatal myocardial infarction and 989 men who had not developed coronary heart disease by 1996 were included. MAIN OUTCOME MEASURES: IgG serum antibodies to C pneumoniae in baseline samples; details of fatal and non-fatal coronary heart disease from medical records and death certificates. RESULTS: 200 (40%) of the 496 men with coronary heart disease were in the top third of C pneumoniae titres compared with 329 (33%) of the 989 controls. The corresponding odds ratio for coronary heart disease was 1.66 (95% confidence interval 1.25 to 2.21), which fell to 1.22 (0.82 to 1.82) after adjustment for smoking and indicators of socioeconomic status. No strong associations were observed between C pneumoniae IgG titres and blood lipid concentrations, blood pressure, or plasma homocysteine concentration. In aggregate, the present study and 14 other prospective studies of C pneumoniae IgG titres included 3169 cases, yielding a combined odds ratio of 1. 15 (0.97 to 1.36), with no significant heterogeneity among the separate studies (chi(2)=10.5, df=14; P>0.1). CONCLUSION: This study, together with a meta-analysis of previous prospective studies, reliably excludes the existence of any strong association between C pneumoniae IgG titres and incident coronary heart disease. Further studies are required, however, to confirm or refute any modest association that may exist, particularly at younger ages.

Circulating inflammatory and hemostatic biomarkers are associated with risk of myocardial infarction and coronary death, but not angina pectoris, in older men.

AIMS: The extent to which hemostatic and inflammatory biomarkers are related to angina pectoris as compared with myocardial infarction (MI) remains uncertain. We examined the relationship between a wide range of inflammatory and hemostatic biomarkers, including markers of activated coagulation, fibrinolysis and endothelial dysfunction and viscosity, with incident myocardial infarction (MI) or coronary heart disease (CHD) death and incident angina pectoris uncomplicated by MI or CHD death in older men. METHODS: A prospective study of 3217 men aged 60-79 years with no baseline CHD (angina or MI) and who were not on warfarin, followed up for 7 years during which there were 198 MI/CHD death cases and 220 incident uncomplicated angina cases. RESULTS: Inflammatory biomarkers [C-reactive protein (CRP), interleukin-6, fibrinogen], plasma viscosity and hemostatic biomarkers [von Willebrand factor (VWF) and fibrin D-dimer] were associated with a significant increased risk of MI/CHD death but not with uncomplicated angina even after adjustment for age and conventional risk factors. Adjustment for CRP attenuated the relationships between VWF, fibrin D-dimer and plasma viscosity with MI/CHD death. Comparisons of differing associations with risk of MI/CHD deaths and uncomplicated angina were significant for the inflammatory markers (P < 0.05) and marginally significant for fibrin D-dimer (P = 0.05). In contrast, established risk factors including blood pressure and high-density lipoprotein (HDL)-cholesterol were associated with both MI/CHD death and uncomplicated angina. CONCLUSION: Circulating biomarkers of inflammation and hemostasis are associated with incident MI/CHD death but not incident angina uncomplicated by MI or CHD death in older men.

Socioeconomic inequalities in coronary heart disease risk in older age: contribution of established and novel coronary risk factors.

BACKGROUND: Evidence on socioeconomic inequalities in coronary heart disease (CHD) and their pathways in the elderly is limited. Little is also known about the contributions that novel coronary risk factors (particularly inflammatory/hemostatic markers) make to socioeconomic inequalities in CHD. OBJECTIVES: To examine the extent of socioeconomic inequalities in CHD in older age, and the contributions (relative and absolute) of established and novel coronary risk factors. METHODS: A population-based cohort of 3761 British men aged 60-79 years was followed up for 6.5 years for CHD mortality and incidence (fatal and non-fatal). Social class was based on longest-held occupation recorded at 40-59 years. RESULTS: There was a graded relationship between social class and CHD incidence. The hazard ratio for CHD incidence comparing social class V (unskilled workers) with social class I (professionals) was 2.70 [95% confidence interval (CI) 1.37-5.35; P-value for trend = 0.008]. This was reduced to 2.14 (95% CI 1.06-4.33; P-value for trend = 0.11) after adjustment for behavioral factors (cigarette smoking, physical activity, body mass index, and alcohol consumption), which explained 38% of the relative risk gradient (41% of absolute risk). Additional adjustment for inflammatory markers (C-reactive protein, interleukin-6, and von Willebrand factor) explained 55% of the relative risk gradient (59% of absolute risk). Blood pressure and lipids made little difference to these estimates; results were similar for CHD mortality. CONCLUSIONS: Socioeconomic inequalities in CHD persist in the elderly and are at least partly explained by behavioral risk factors; novel (inflammatory) coronary risk markers made some further contribution. Reducing inequalities in behavioral factors (especially cigarette smoking) could reduce these social inequalities by at least one-third.

The value of gamma-glutamyltransferase in cardiovascular risk prediction in men without diagnosed cardiovascular disease or diabetes.

AIMS: We have examined the relationship between gamma-glutamyltransferase (GGT) and major coronary heart disease (CHD) and stroke events and cardiovascular mortality in men free of cardiovascular disease (CVD). METHODS: A prospective study of 6997 men aged 40-59 with no history of CVD (CHD or stroke) or diabetes drawn from general practices in 24 British towns and followed up for 24 years. RESULTS: GGT was significantly and positively associated with increased risk of fatal (but not non-fatal CHD events), major stroke events and total CVD mortality after adjustment for established CVD risk factors. Risk of fatal CHD and CVD mortality was only elevated in the top quarter (22IU/L); risk of stroke tended to increase with increasing GGT. The adjusted relative risks (Q4 vs. Q1) were 1.43 (1.09,1.84) for fatal CHD events, 1.56 (1.20,2.04) for stroke incidence and 1.40 (1.16,1.70) for CVD mortality. When stratified by age groups stronger associations were seen between GGT and CVD mortality in the younger men (<55 years) (p=0.01 for interaction). GGT significantly predicted CVD outcomes especially in those at low and medium CHD risk based on Framingham risk score (FRS). CONCLUSION: Elevated GGT is associated with significantly increased risk of stroke, fatal CHD events and CVD mortality independent of established CVD risk factors and may be a useful additional marker for long-term CVD risk.

Serum matrix metalloproteinase-9 and coronary heart disease: a prospective study in middle-aged men.

BACKGROUND: Matrix metalloproteinase-9 (MMP-9) has a potential role in arterial plaque rupture, but its relation to risk of coronary heart disease (CHD) is uncertain. AIM: To determine whether circulating levels of serum MMP-9 are prospectively related to the risk of CHD in the general population. METHODS: We measured baseline MMP-9 levels in stored serum samples of subjects in a case-control study nested within a prospective study of 5661 men followed up for 16 years for CHD events (465 cases, 1076 controls). RESULTS: MMP-9 values were associated with cigarette smoking, and with several inflammatory and haemostatic markers, but not with age, body mass index, blood pressure or lipid measurements. Men in the top third of baseline MMP-9 levels had an age-adjusted odds ratio (OR) for CHD of 1.37 (95% CI 1.04-1.82) compared with those in the bottom third. Adjustment for conventional risk factors (smoking in particular) reduced the odds ratio to borderline significance: OR 1.28 (95% CI 0.95-1.74), while additional adjustment for two markers of generalized inflammation, interleukin-6 and C-reactive protein, further attenuated the association: OR 1.13 (0.82-1.56). CONCLUSION: Serum MMP-9 has a modest association with incident CHD in the general population, which is not independent of cigarette smoking exposure and circulating markers of generalized inflammation. MMP-9 is unlikely to be a clinically useful biomarker of CHD risk, but may still play a role in the pathogenesis of CHD.

Cardiovascular disease incidence and mortality in older men with diabetes and in men with coronary heart disease.

OBJECTIVE: To examine the relation of diabetes and coronary heart disease (CHD; myocardial infarction (MI) or angina) to the incidence of major CHD and stroke events and total mortality. METHODS: Prospective study of 5934 men aged 52-74 years followed up for 10 years. The men were divided into five groups according to their diabetes and CHD status. RESULTS: During the follow up there were 662 major CHD events, 305 major stroke events, and 1357 deaths from all causes (637 cardiovascular disease (CVD) deaths, 417 CHD deaths). Men with diabetes had significantly increased cardiovascular and total mortality risk compared with non-diabetic men with no CHD but lower risk than men with prior MI only. The adjusted relative risk for CHD deaths was 2.82 (95% confidence interval (CI) 1.85 to 4.28) in men with diabetes only, 2.12 (95% CI 1.53 to 2.93) in men with angina only, 3.91 (95% CI 3.07 to 4.99) in men with MI, and 8.93 (95% CI 6.13 to 12.99) in men with both diabetes and CHD. Case fatality among men with diabetes only was similar to those with prior MI only. CHD and CVD mortality increased with increasing duration of diabetes with risk eventually approaching that of patients with MI without diabetes. CONCLUSION: Men with diabetes only have a CVD risk intermediate between men with angina and men with prior MI. Their absolute risk is high and the prognosis for diabetic patients who develop CHD is extremely poor.