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.

Do women exhibit greater differences in established and novel risk factors between diabetes and non-diabetes than men? The British Regional Heart Study and British Women's Heart Health Study.

AIMS/HYPOTHESIS: Type 2 diabetes is associated with greater relative risk of CHD in women than in men, which is not fully explained by conventional cardiovascular risk factors. We assessed whether cardiovascular risk factors including more novel factors such as markers of insulin resistance, inflammation, activated coagulation and endothelial dysfunction differ more between diabetic and non-diabetic women than between diabetic and non-diabetic men, and the role of insulin resistance. METHODS: A cross-sectional study of non-diabetic and diabetic men and women (n = 7,529) aged 60-79 years with no previous myocardial infarction who underwent an examination was conducted. Measurements of anthropometry, blood pressure and fasting measurements of lipids, insulin, glucose and haemostatic and inflammatory markers were taken. RESULTS: Non-diabetic women tended to have more favourable risk factors and were less insulin resistant than non-diabetic men, but this was diminished in the diabetic state. Levels of waist circumference, BMI, von Willebrand factor (VWF), WBC count, insulin resistance (HOMA-IR), diastolic blood pressure, HDL-cholesterol, tissue plasminogen activator (t-PA) and factor VIII differed more between diabetic and non-diabetic women than between diabetic and non-diabetic men (test for diabetes × sex interaction p < 0.05). The more adverse effect of diabetes on these risk markers in women was associated with, and thereby largely attenuated by, insulin resistance. CONCLUSIONS/INTERPRETATION: The greater adverse influence of diabetes per se on adiposity and HOMA-IR and downstream blood pressure, lipids, endothelial dysfunction and systemic inflammation in women compared with men may contribute to their greater relative risk of coronary heart disease.

The potential for a two-stage diabetes risk algorithm combining non-laboratory-based scores with subsequent routine non-fasting blood tests: results from prospective studies in older men and women.

AIM: To develop strategies based on simple clinical assessment and blood markers to identify older individuals at high risk for Type 2 diabetes. METHODS: A prospective study of non-diabetic men (n = 3523) and women (n = 3404) aged 60-79 years followed for 7 years, during which there were 297 incident cases of Type 2 diabetes. Logistic regression was used to develop scores to predict incident cases, starting with clinical predictors and adding blood markers that predicted the incidence of diabetes. Receiving operating characteristic analyses were used to assess improvement in prediction. RESULTS: The area under the curve for a simple clinical assessment score, which included age, sex, family history of diabetes, smoking status, BMI, waist circumference, hypertension and recall of doctor diagnosis of coronary heart disease was 0.765 (0.740, 0.791); sensitivity and specificity in the top quintile of the score were 50.3 and 81.4%, respectively. Addition of simple fasting blood markers HDL cholesterol, triglyceride and glucose improved prediction [area under the curve = 0.817 (0.793, 0.840), P < 0.0001; sensitivity 63.8%; specificity 82.0%]. An alternative model adding blood markers not dependent on fasting yielded similar results. Further addition of C-reactive protein made no improvement. Blood measurements made small differences to reclassification of risk in those in the lowest three quintiles of the non-laboratory score. CONCLUSION: In large population settings, simple clinical assessments could be used in the first instance to identify older adults who would benefit from further testing with routine (non-fasting) blood markers to identify those at most likely to be at elevated diabetes risk.

Assessing prediction of diabetes in older adults using different adiposity measures: a 7 year prospective study in 6,923 older men and women.

AIMS/HYPOTHESIS: The aim of this study was to examine whether waist circumference (WC) or WHR improve diabetes prediction beyond body mass index in older men and women, and to define optimal cut-off points. METHODS: In this prospective study, non-diabetic men (n = 3,519) and women (n = 3,404) aged 60-79 years were followed up for 7 years. There were 169 and 128 incident cases of type 2 diabetes in men and women, respectively. RESULTS: BMI, WC and WHR all showed strong associations with incident type 2 diabetes independent of potential confounders. In men, the adjusted relative risks (top vs lowest quartile) were 4.71 (95% CI 2.45-9.03) for BMI, 3.53 (95% CI 1.92-6.48) for WC and 2.76 (95% CI 1.58-4.82) for WHR. For women, the corresponding relative risks were 4.10 (95% CI 2.16-7.79), 12.18 (95% CI 4.83-30.74) and 5.61 (95% CI 2.84-11.09) for BMI, WC and WHR, respectively. Receiver-operating characteristic curve analysis revealed similar associations for BMI and WC in predicting diabetes in men (AUC = 0.726 and 0.713, respectively); WHR was the weakest predictor (AUC = 0.656). In women, WC was a significantly stronger predictor (AUC = 0.780) than either BMI (AUC = 0.733) or WHR (AUC = 0.728; p < 0.01 for both). Inclusion of both WC and BMI did not improve prediction beyond BMI alone in men or WC alone in women. Optimal sensitivity and specificity for the prediction of type 2 diabetes was observed at a WC of 100 cm in men and 92 cm in women. CONCLUSIONS/INTERPRETATION: In older men, BMI and WC yielded similar prediction of risk of type 2 diabetes, whereas WC was clearly a superior predictor in older women.

The detection, treatment and control of high blood pressure in older British adults: cross-sectional findings from the British Women's Heart and Health Study and the British Regional Heart Study.

Among older people, the detection and control of hypertension is particularly important to reduce cardiovascular disease risk. This cross-sectional survey aimed to describe the detection, treatment and control of hypertension in older British adults. A total of 3059 women and 3007 men aged 60-79 years were randomly selected from general practice age/sex registers in 24 British towns and examined from 1998 to 2001. Of these, 52.6% women and 47.9% men had at least one indicator of hypertension (high blood pressure on examination, or taking antihypertensive medication or recalled a doctor diagnosis of high blood pressure). Among women, 50% of those with any indication of hypertension were on treatment and 29% were well controlled, and among men 45% were on treatment and 16% were well controlled. With the exception of alcohol use in men (adjusted odds ratio 0.67 (0.46, 0.98)), socioeconomic factors, area of residence and behavioural risk factors were not associated with good control among those with hypertension in either sex. Of those on treatment, 20.7% of women and 28% of men were on two classes of antihypertensive medication and 3.5 and 4.9%, respectively, were on three or more classes of antihypertensive medication. Among those with a doctor diagnosis of hypertension and taking antihypertensive medication, the proportion with well controlled blood pressure did not differ between those on more than one antihypertensive and those on just one in either sex. We conclude that targets of good control are rarely met in older individuals, who would benefit from the associated reduction in cardiovascular disease risk.

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.

Femoral atherosclerosis in an older British population: prevalence and risk factors.

Most estimates of the prevalence of peripheral atherosclerosis have been based on intermittent claudication or lower limb blood flow. The aim of this study was therefore to determine the prevalence of underlying femoral plaque, and to determine its association with other cardiovascular disease and risk factors. Presence of plaque was identified using ultrasound in a random sample of men (n=417) and women (n=367) aged 56-77 years. Coexistent cardiovascular disease, exercise and smoking were determined by questionnaire, blood pressure was recorded, and serum cholesterol and plasma fibrinogen were determined. Of the 784 subjects that were scanned, 502 (64%) demonstrated atherosclerotic plaque. Disease prevalence increased significantly with age (P<0.0001), and was more common in men (67.1 vs. 59.4%, P<0.05). Subjects with femoral plaque had a significantly greater odds of previous ischaemic heart disease (OR 2. 2, 95% CI 1.3, 3.7) and angina (OR 1.7, 95% CI 1.03, 2.7), but not of stroke or leg pain on exercise. Current and ex-smoking, raised serum total cholesterol and plasma fibrinogen levels, but not blood pressure, were associated with an increased risk of femoral plaque, independent of age and sex. Frequent exercise and a high HDL cholesterol were significantly associated with lower risk. In conclusion, therefore, atherosclerotic disease of the femoral artery affects almost two-thirds of the population in late middle age. It is associated with an increased prevalence of ischaemic heart disease and angina, but whether detecting at risk individuals using ultrasound offers advantages over simpler and less expensive risk factor scoring requires evaluation in trials.

Childhood blood pressure, body build, and birthweight: geographical associations with cardiovascular mortality.

STUDY OBJECTIVE: The aim was to examine whether blood pressure, body build, and birthweight differ between areas of England and Wales with widely differing adult cardiovascular mortality rates. DESIGN: This was a cross sectional survey of children in five towns with exceptionally high and five towns with exceptionally low current adult cardiovascular mortality. SETTING: The study was a school based survey. SUBJECTS: 3842 children aged 5.0-7.5 years were selected by stratified random sampling of primary schools (response rate 76%). MEASUREMENTS AND MAIN RESULTS: Blood pressure, pulse rate, height, and weight were measured and birthweight was assessed by maternal recall. Children in towns with high cardiovascular mortality rates were significantly shorter than those in towns with low cardiovascular mortality rates (mean difference 0.9 cm, 95% confidence interval 0.4 to 1.4 cm) and had slightly higher body mass indices (mean difference 0.12 kg/m2, 95% CI -0.03 to 0.27 kg/m2). Mean birthweights were slightly lower in high mortality towns (mean difference 34 g, 95% CI -10 to 78 g), while the proportion of children with low birthweight (< 2500 g) (8.1%) was significantly higher than that in low mortality towns (5.5%) (p = 0.005). Mean differences in blood pressure between high and low mortality towns were small and non-significant, even after adjustment for height. The differences in height between high and low mortality towns were largely independent of social class. However, differences in mean birthweight were markedly reduced once social class was taken into account. CONCLUSIONS: No geographical relationship between childhood blood pressure and adult cardiovascular mortality was detected. Although it is possible that the differences in mean height and body mass index between towns with differing adult cardiovascular mortality may have implications for future patterns of health in these towns, the absence of marked differences in birthweight and blood pressure suggests that hypotheses proposing a direct relationship between intrauterine experience and adult cardiovascular mortality will have limited relevance to geographical variation in cardiovascular disease in this generation.

Maternal factors and development of cardiovascular risk: evidence from a study of blood pressure in children.

It has been suggested that risks of hypertension and cardiovascular disease begin in utero and that maternal nutrition plays an important role. We have examined the relation between maternal factors and BP in a study of 1,311 children in which physical measurements at 9-11 years of age have been linked to a parental questionnaire; birth record data were also available in a subsample of 662 children. Maternal height was inversely related to childhood BP after adjustment for the child's current height. However, several social factors related to maternal nutrition in pregnancy in earlier studies (including social class, housing tenure, maternal educational attainment and maternal smoking in pregnancy) showed weak and inconsistent relations with BP at 9-11 years. Minimum maternal haemoglobin in pregnancy and change in mean corpuscular volume in pregnancy (identified as potentially important markers of maternal nutrition in earlier studies) showed no consistent relationships either with placental weight to birthweight ratio or with childhood BP, although both factors showed strong inverse associations with birthweight. The association between maternal height and childhood BP may reflect the influence of early life factors on cardiovascular risk. However, the absence of consistent relationships between social factors and BP in offspring provides little support for the possibility that maternal diet is an important influence on cardiovascular risk factors in childhood. Minimum maternal haemoglobin and change in maternal mean corpuscular volume are unlikely to be specific markers of maternal nutrition in pregnancy. More specific hypotheses relating maternal nutrition to the development of cardiovascular risk in offspring are required.

Scoring system to identify men at high risk of stroke: a strategy for general practice.

BACKGROUND: The major risk factors for stroke are well described and there is good evidence that the risks associated with hypertension and cigarette smoking are reversible by appropriate interventions. However, if disease prevention measures are to be efficient, it is important that a system which can identify individuals at high risk of stroke be available for use in general practice. AIM: A study was therefore undertaken to design an effective and practical system for detecting men aged 40 to 59 years at high risk of stroke in primary care. METHOD: Stroke incidence and risk factor data were examined in a cohort of 7735 men aged 40 to 59 years who had taken part in the British regional heart study. Analysis was performed using data from initial entry into the study and then from five and 11.5 years of follow up. Subjects were randomly selected from the age-sex register of one general practice in each of 24 different towns throughout the United Kingdom, representing the full range of cardiovascular mortality rates. RESULTS: A simple scoring system derived from logistic regression using age, systolic blood pressure, current cigarette consumption, and evidence of anginal chest pain was able to detect more than 80% of all strokes occurring within five years in the top fifth of the score distribution. The inclusion of other risk factors for stroke did not increase the score's predictive ability. The combination of smoking and hypertension, while much less sensitive than the scoring system, was a better indicator of risk than any single risk factor, all of whose predictive values were poor. CONCLUSION: Based on readily measured variables, this scoring system could be used in general practice to identify men at high risk of stroke who would benefit from further intervention. Effective identification of high risk individuals requires assessment of the combined effects of multiple risk factors.

Birth weight and blood pressure: cross sectional and longitudinal relations in childhood.

OBJECTIVE: To examine cross sectional and longitudinal relations between birth weight and blood pressure in childhood. DESIGN: Cross sectional study of primary school children aged 9-11 years, with analysis in relation to previous measurements at 5-7 years in a subgroup. SETTING: 20 primary schools in Guildford and Carlisle. SUBJECTS: 1511 children measured at 9-11 years (response rate 79%), including 549 who had been measured at 5-7 years. MAIN OUTCOME MEASURES: Blood pressure at 9-11 years, change in blood pressure between 5-7 and 9-11 years, birth weight (based on maternal recall), and placental weight (based on birth records). RESULTS: At 9-11 years birth weight was inversely related both to systolic blood pressure (regression coefficient -2.80 mm Hg/kg; 95% confidence interval -3.84 to -1.76) and to diastolic blood pressure (regression coefficient -1.42 mm Hg/kg; -2.14 to -0.70) once current height and body mass index were taken into account. Placental weight was inversely related to blood pressure after adjustment for current height and body mass index but placental ratio (placental weight to birth weight) was unrelated to blood pressure. Between 5-7 and 9-11 years systolic blood pressure rose more rapidly in children of lower birth weight (regression coefficient -1.71 mm Hg/kg; -3.35 to -0.07). This effect seemed to be stronger in girls. CONCLUSIONS: Birth weight rather than placental ratio is the early life factor most importantly related to blood pressure in childhood. The results support the possibility of "amplification" of the relation between birth weight and blood pressure, particularly in girls.

Cardiovascular risk factors in British children from towns with widely differing adult cardiovascular mortality.

OBJECTIVE: To examine whether cardiovascular risk factors differ in children from towns in England and Wales with widely differing adult cardiovascular death rates. DESIGN: School based survey conducted during 1994 in 10 towns, five with exceptionally high adult cardiovascular mortality (standardised mortality ratio 131-143) and five with exceptionally low adult cardiovascular mortality (64-75). Towns were surveyed in high-low pairs. SUBJECTS: 3415 white children aged 8-11 years with physical measurements (response rate 75%), including 1287 with blood samples (response rate 64%), of whom 515 had blood samples taken 30 minutes after a glucose load. RESULTS: Children in towns with high cardiovascular mortality were on average shorter than those in towns with low mortality (mean difference 1.2 cm; 95% confidence interval 0.3 to 2.1 cm; P = 0.02) and had a higher ponderal index (0.34 kg/m3; 0.16 to 0.52 kg/m3; P = 0.006). Mean systolic pressure was higher in high mortality towns, particularly after adjustment for height (2.0 mm Hg; 0.8 to 3.2 mm Hg; P = 0.009). Mean waist:hip ratio, total cholesterol concentration, and 30 minute post-load glucose measurements were similar in high and low mortality towns. The differences in height and blood pressure between high and low mortality towns were unaffected by standardisation for birth weight. CONCLUSIONS: The differences in height, ponderal index, and blood pressure between towns with high and low cardiovascular mortality, if persistent, may have important future public health implications. Their independence of birth weight suggests that the childhood environment rather than the intrauterine environment is involved in their development.

Passive exposure to tobacco smoke in children aged 5-7 years: individual, family, and community factors.

OBJECTIVE: To examine the importance of parental smoking on passive exposure to tobacco smoke in children and the social and geographical patterns of exposure. DESIGN: Cross sectional study. SETTING: Schools in 10 towns in England and Wales; five towns with high adult cardiovascular mortality and five with low rates. SUBJECTS: 4043 children aged 5-7 years of European origin. MAIN OUTCOME MEASURES: Salivary cotinine concentration and parents self reported smoking habits. RESULTS: 1061 (53.0%) children were exposed to cigarette smoke at home or by an outside carer. Geometric mean cotinine rose from 0.29 (95% confidence interval 0.28 to 0.31) ng/ml in children with no identified exposure to 4.05 (3.71 to 4.42) ng/ml in households where both parents smoked and 9.03 (6.73 to 12.10) ng/ml if both parents smoked more than 20 cigarettes a day. The effect of mothers' smoking was greater than that of fathers', especially at high levels of consumption. After adjustment for known exposures geometric mean cotinine concentrations rose from 0.52 ng/ml in social class I to 1.36 ng/ml in social class V (P < 0.0001); and were doubled in high mortality towns compared with the low mortality towns (P = 0.002). In children with no identified exposure similar trends by social class and town were observed and the cotinine concentrations correlated with the prevalence of parental smoking, both between towns (r = 0.69, P = 0.02) and between schools within towns (r = 0.50, P < 0.001). CONCLUSIONS: Mothers' smoking is more important that fathers' despite the lower levels of smoking by mothers. Children not exposed at home had low cotinine concentration, the level depending on the prevalence of smoking in the community.

Size at birth and blood pressure: cross sectional study in 8-11 year old children.

OBJECTIVE: To identify which patterns of fetal growth, represented by different measurements of size at birth, are associated with increased blood pressure in children aged 8-11 years. DESIGN AND SETTING: School based, cross sectional survey conducted in 10 towns in England and Wales in 1994. SUBJECTS: 3010 singleton children (response rate 75%) with physical measurements and information on birth weight from parental questionnaires. Hospital birth records were examined for 1573. MAIN OUTCOME MEASURES: Systolic and diastolic blood pressure at age 8-11 years. RESULTS: In the whole group birth weight was inversely related to systolic pressure (regression coefficient -1.48 mm Hg/kg; 95% confidence interval -2.20 to -0.76) after adjustment for current body size. There was no significant association between birth weight and diastolic pressure. The association with systolic pressure was much stronger in girls (-2.54 mm Hg/kg; -3.60 to -1.48) than in boys (-0.64 mm Hg/kg; -1.58 to 0.30), with a significant difference between the sexes (P = 0.006). Among the other neonatal measures, head circumference and placental weight were inversely associated with subsequent blood pressure in girls, and placental ratio (placental weight:birth weight) was positively associated with blood pressure in boys. Neither ponderal index at birth nor length:head circumference ratio was related to blood pressure in either sex. CONCLUSIONS: In these contemporary children the association between birth weight and blood pressure was apparent only in girls. There was no evidence that measures of size at birth, which may be related to nutrition at critical periods of pregnancy (thinness at birth or shortness in relation to head circumference), are related to blood pressure in the offspring.

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.

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.