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.

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.

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.

Inequalities in coronary revascularisation during the 1990s: evidence from the British regional heart study.

OBJECTIVE: To investigate the influence of age and social circumstances on probability of revascularisation among British men. DESIGN: Prospective population based study SETTING: 24 medium sized British towns, none of which contained a hospital undertaking coronary artery bypass surgery. SUBJECTS: 5814 surviving participants of the BRHS (British regional heart study), aged 52-73 years, with no history of revascularisation when responding to a questionnaire in November 1992. MAIN OUTCOMES: Incident coronary revascularisations, as documented in general practitioner records, over the following 7.1 years and coronary angiography investigations reported by men in a further questionnaire in November 1996. RESULTS: 160 men underwent at least one revascularisation during this period (4.2/1000 person-years). In multifactorial analysis, which included adjustment for incidence of major coronary heart disease or angina, a lower incidence of revascularisation was found among men aged over 65 years in November 1992 (hazard ratio 0.62, 95% confidence interval (CI) 0.44 to 0.87), among men with manual occupations (0.73, 95% CI 0.53 to 1.02), among men living in households possessing no car (0.44, 95% CI 0.24 to 0.80) or one car (0.60, 95% CI 0.42 to 0.87) compared with two or more cars, among council tenants (0.49, 95% CI 0.25 to 0.97), and among men living outside southern England (0.71, 95% CI 0.51 to 0.99). Only car ownership was related to the incidence of diagnostic angiography: the odds ratio for angiography for those owning fewer than two cars was 0.62 (95% CI 0.42 to 0.89). CONCLUSION: During the 1990s, there were major inequalities in the probability of undergoing coronary revascularisation between British men according to socioeconomic status, age, and geographic location.

Low prevalence of lipid lowering drug use in older men with established coronary heart disease.

OBJECTIVE: To determine the prevalence and correlates of lipid lowering drug use among older British men with established coronary heart disease (CHD). DESIGN: Cross sectional survey within a cohort study (British regional heart study) carried out at 20 years of follow up in 1998-2000. SETTING: General practices in 24 British towns. PARTICIPANTS: 3689 men aged 60-75 years (response rate 76%). MAIN OUTCOME MEASURES: Diagnoses of myocardial infarction and angina based on detailed review of general practice records. Lipid lowering drug use and blood cholesterol concentrations ascertained at 20 year follow up examination. RESULTS: Among 286 men with definite myocardial infarction, 102 (36%) were taking a lipid lowering drug (93 (33%) a statin); among 360 men with definite angina without myocardial infarction, 84 (23%) were taking a lipid lowering drug (78 (21%) a statin). Most men with documented CHD who were not receiving a lipid lowering drug had a total cholesterol concentration of 5.0 mmol/l or more (87% of those with myocardial infarction, 82% with angina). Fewer than half of men with CHD receiving a statin had a total cholesterol concentration below 5.0 mmol/l (45% of those with myocardial infarction and 47% of those with angina). Only one third of the men taking a statin were receiving trial validated dosages. Among men with CHD, a history of revascularisation, more recent diagnosis, and younger age at diagnosis were associated with a higher probability of receiving lipid lowering drug treatment. CONCLUSION: Among patients with established CHD, the prevalence of lipid lowering drug use remains low and statin regimens suboptimal. Major improvements in secondary prevention are essential if the benefits of statins are to be realised.

Soluble adhesion molecules and prediction of coronary heart disease: a prospective study and meta-analysis.

BACKGROUND: Previous studies have suggested that circulating concentrations of soluble adhesion molecules are useful predictors of risk of coronary heart disease (CHD). Larger studies are needed, however, to test this hypothesis. METHODS: We measured serum concentrations of four soluble cell adhesion molecules (intercellular adhesion molecule-1 [ICAM-1], vascular cell adhesion molecule-1 [VCAM-1], E-selectin, and P-selectin) in the stored baseline serum samples of 643 men with coronary heart disease and 1278 controls nested in a prospective sutdy of 5661 men who were monitored for 16 years. We also did a meta-analysis of previous relevant studies to place our findings in context. RESULTS: Concentrations of soluble adhesion molecules were significantly associated with one another, with other markers of inflammation, and with some classic coronary risk factors. For ICAM-1, the odds ratio for CHD was 1.68 (95% CI 1.32-2.14) in a comparison of men in the top third with those in the bottom third of baseline measurements after adjustments for age and town. This decreased to 1.11 (0.75-1.64) after adjustment for some classic coronary risk factors and indicators of socioeconomic status. For the three other cell adhesion molecules, the odds ratios for CHD, first adjusted for age and town only, and then additionally adjusted for other risk factors, were: VCAM-1: 1.26 (0.99-1.61) and 0.96 (0.66-1.40); E-selectin: 1.27 (1.00-1.61) and 1.13 (0.78-1.62); and P-selectin: 1.23 (0.96-1.56) and 1.20 (0.81-1.76). INTERPRETATION: The measurement of these adhesion molecules is unlikely to add much predictive information to that provided by more established risk factors.

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.

Fibrinogen and factor VII levels are related to adiposity but not to fetal growth or social class in children aged 10-11 years.

Factors operating in fetal life or during childhood may be important in determining fibrinogen and factor VII concentrations in adult life, and particularly in explaining social gradients in cardiovascular disease risk. In 1994, the authors measured fibrinogen and factor VIIc levels in 641 children aged 10-11 years (61% response rate) from schools in five towns in England and Wales. Birth weight was obtained by maternal recall, and other data on measures of fetal growth were obtained from birth records. Fibrinogen levels were higher in girls (258.8 mg/dl) than in boys (245.4 mg/dl) (95% confidence interval (CI) for difference: 5.5, 21.5). Fibrinogen and factor VIIc levels were linearly related to adiposity, rising by 37.1 mg/dl (95% CI: 24.7, 49.5) and 13.0% of standard (95% CI: 6.3, 19.7), respectively, between the bottom and top quintiles of ponderal index (weight (kg)/height (m)3). Fibrinogen was independently related to heart rate (p < 0.001) and was negatively but nonsignificantly related to measures of physical activity. Factor VIIc was positively correlated with total cholesterol (p < 0.001). No relations were found with measures of fetal growth or social class. These data do not support the concept that fibrinogen or factor VII levels are determined in utero or by social factors in childhood. Adiposity and physical training appear to be the important determinants of fibrinogen and factor VII levels in childhood.

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

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

Flow-mediated dilation in 9- to 11-year-old children: the influence of intrauterine and childhood factors.

BACKGROUND: Early life factors, particularly size at birth, may influence later risk of cardiovascular disease, but a mechanism for this influence has not been established. We have examined the relation between birth weight and endothelial function (a key event in atherosclerosis) in a population-based study of children, taking into account classic cardiovascular risk factors in childhood. METHODS AND RESULTS: We studied 333 British children aged 9 to 11 years in whom information on birth weight, maternal factors, and risk factors (including blood pressure, lipid fractions, preload and postload glucose levels, smoking exposure, and socioeconomic status) was available. A noninvasive ultrasound technique was used to assess the ability of the brachial artery to dilate in response to increased blood flow (induced by forearm cuff occlusion and release), an endothelium-dependent response. Birth weight showed a significant, graded, positive association with flow-mediated dilation (0.027 mm/kg; 95% CI, 0.003 to 0.051 mm/kg; P=.02). Childhood cardiovascular risk factors (blood pressure, total and LDL cholesterol, and salivary cotinine level) showed no relation with flow-mediated dilation, but HDL cholesterol level was inversely related (-0.067 mm/mmol; 95% CI, -0.021 to -0.113 mm/mmol; P=.005). The relation between birth weight and flow-mediated dilation was not affected by adjustment for childhood body build, parity, cardiovascular risk factors, social class, or ethnicity. CONCLUSIONS: Low birth weight is associated with impaired endothelial function in childhood, a key early event in atherogenesis. Growth in utero may be associated with long-term changes in vascular function that are manifest by the first decade of life and that may influence the long-term risk of cardiovascular disease.

Effect of fresh fruit consumption on lung function and wheeze in children.

BACKGROUND: Fresh fruit consumption and vitamin C intake have been associated with improved lung function in adults. Whether this is due to enhancement of lung growth, to a reduction in lung function decline, or to protection against bronchospasm is unclear. METHODS: In a cross-sectional school based survey of 2650 children aged 8-11 from 10 towns in England and Wales the main outcome measure was forced expiratory volume in one second (FEV1) standardised for body size and sex. Exposure was assessed by a food frequency questionnaire to parents and by measurement of plasma levels of vitamin C in a subsample of 278 children. RESULTS: FEV1 was positively associated with frequency of fresh fruit consumption. After adjustment for possible confounding variables including social class and passive smoking, those who never ate any fresh fruit had an estimated FEV1 some 79 ml (4.3%) lower than those who ate these items more than once a day (95% CI 22 to 136 ml). The association between FEV1 and fruit consumption was stronger in subjects with wheeze than in non-wheezers (p = 0.020 for difference in trend), though wheeze itself was not related to fresh fruit consumption. Frequency of consumption of salads and of green vegetables were both associated with FEV1 but the relationships were weaker than for fresh fruit. Plasma vitamin C levels were unrelated to FEV1 (r = -0.01, p = 0.92) or to wheeze and were only weakly related to fresh fruit consumption (r = 0.13, p = 0.055). CONCLUSIONS: Fresh fruit consumption appears to have a beneficial effect on lung function in children. Further work is needed to confirm whether the effect is restricted to subjects who wheeze and to identify the specific nutrient involved.