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Biomedical subjects

Peter H Whincup

Publications and source records attributed to Peter H Whincup.

At least 19 recordsLinked to original sources
PubMed2006

Renal function and cardiovascular mortality in elderly men: the role of inflammatory, procoagulant, and endothelial biomarkers.

AIMS: To assess the extent to which inflammatory, procoagulant, and endothelial biomarkers modify the relationship between diminished renal function and cardiovascular mortality. METHODS AND RESULTS: Prospective study of 4029 men aged 60-79 years followed up for a mean period of 6 years, during which 304 cardiovascular deaths occurred. Predicted estimated glomerular filtration rate (eGFR) was used as a measure of renal function. Reduced eGFR was associated with increased prevalence of established cardiovascular risk factors [cardiovascular disease, diabetes, hypertension, left ventricular (LV) hypertrophy, and dyslipidaemia] and higher levels of inflammatory markers [interleukin 6 (IL-6), C-reactive protein], endothelial markers [von Willebrand factor (vWF) and tissue plasminogen activator], activated coagulation markers (fibrin D-dimer), and blood viscosity. Cardiovascular mortality risk increased with decreasing levels of eGFR, particularly among men with eGFR <60 mL/min per 1.73 m(2) even after adjustment for established risk factors (adjusted RR 1.49, 95% CI 1.10, 2.03; <60 vs. > or =70 mL/min per 1.73 m(2)). The association was attenuated after further adjustment for vWF, D-dimer, and IL-6 (adjusted RR 1.34, 95% CI 0.98-1.82). CONCLUSION: Mild-to-moderate renal insufficiency is associated with significantly increased cardiovascular mortality in elderly men, which is partly explained by the increased prevalence of established risk factors, markers of coagulation, endothelium, and inflammation.

Aged↗
PubMed2006

Adiponectin and coronary heart disease: a prospective study and meta-analysis.

BACKGROUND: There is uncertainty about the association between circulating concentrations of adiponectin and coronary heart disease (CHD) risk. We report new data from a prospective study in the context of a meta-analysis of previously published prospective studies. METHODS AND RESULTS: We measured baseline adiponectin levels in stored serum samples of 589 men with fatal CHD or nonfatal myocardial infarction and in 1231 controls nested within a prospective study of 5661 men (aged 40 to 59 years) recruited during 1978-1980, as well as in paired samples obtained 4 years apart from 221 of these participants. Baseline adiponectin concentrations correlated (P < 0.0001) positively with HDL cholesterol (r = 0.33) and inversely with C-reactive protein (r = -0.11) and BMI (r = -0.21), and the year-to-year consistency of adiponectin values was comparable to those of blood pressure and total cholesterol levels. No significant difference between median adiponectin levels at baseline was observed between cases and controls (10.2 versus 10.8 microg/mL; P = 0.5), despite the fact that body mass index, HDL, and C-reactive protein were all significant predictors of events in this cohort. The odds ratio for CHD was 0.89 (95% CI, 0.67 to 1.18) in a comparison of men in the top third of adiponectin concentrations compared with those in the bottom third, similar to a meta-analysis (including the present study) of 7 prospective studies involving a total of 1318 CHD cases (odds ratio, 0.84 [95% CI, 0.70 to 1.01]). CONCLUSIONS: In contrast to the strong associations previously reported between adiponectin levels and risk of type 2 diabetes, any association with CHD risk is comparatively moderate and requires further investigation.

Adiponectin↗
PubMed2006

The relations of body composition and adiposity measures to ill health and physical disability in elderly men.

Although body build is related to disability and mortality in older people, the independent contributions of adiposity and lean mass are not fully defined. The authors examined the relations of body composition (fat mass index, fat-free mass index) and adiposity (body mass index, waist circumference) to ill health and physical disability in a cross-sectional study of 4,252 British men aged 60-79 years in 1998-2000. Increased body mass index, waist circumference, and fat mass index were associated with increased prevalence of cardiovascular disease, overall ill health, and disability. Adjusted odds ratios of cardiovascular disease (top vs. bottom fifth) were 1.58 (95% confidence interval (CI): 1.23, 2.03) for fat mass index, 1.45 (95% CI: 1.14, 1.86) for body mass index, and 1.27 (95% CI: 0.99, 1.62) for waist circumference. For overall "poor/fair" health, the corresponding odds ratios were 1.71 (95% CI: 1.33, 2.21), 1.49 (95% CI: 1.17, 1.90), and 1.64 (95% CI: 1.28, 2.09) and, for mobility limitation, they were 1.56 (95% CI: 1.17, 2.06), 1.96 (95% CI: 1.48, 2.56), and 1.88 (95% CI: 1.42, 2.49). A high fat-free mass index was associated with only a decreased prevalence of respiratory problems and cancer (odds ratios=0.45 (95% CI: 0.33, 0.62) and 0.62 (95% CI: 0.42, 0.94), respectively). Body fatness, not fat-free mass, is associated with cardiovascular disease and disability in older men. Simple measures of overweight, such as body mass index and waist circumference, are good indicators of the likelihood of morbidity in older men. Prevention of weight gain with increasing age is likely to reduce morbidity and disability among older men.

Adiposity↗
PubMed2006

Secondary prevention of coronary heart disease in older patients after the national service framework: population based study.

OBJECTIVE: To examine the extent of uptake of medication for secondary prevention of coronary heart disease in older British men and women before (1998-2001) and after (2003) the implementation of the national service framework. DESIGN: Two population based, longitudinal studies of men and women aged 60-79 in 1998-2001, based in one general practice in each of 24 British towns. PARTICIPANTS: Men and women with established coronary heart disease at the two time points (respectively 817 and 465 in 1998-2001, 857 and 548 in 2003), aged 60-79 in 1998-2001. MAIN OUTCOME MEASURES: Prevalence of use of antiplatelet medication, statins, beta blockers, angiotensin converting enzyme (ACE) inhibitors, and other blood pressure lowering treatments (individually and in combination) assessed in 1998-2001 and 2003. RESULTS: Between 1998-2001 and 2003, the use of all individual drugs had increased in both men and women, especially for statins (from 34% to 65% in men and from 48% to 67% in women with myocardial infarction). However, less than half received beta blockers and ACE inhibitors, even by 2003. Prevalences of medication use were lower in patients with angina than in those with myocardial infarction. The proportions of patients receiving more than one drug increased over time; by 2003 about half of patients with myocardial infarction and a third of those with angina were receiving antiplatelet medication, statins, and blood pressure lowering treatments. CONCLUSIONS: Between 1998-2001 and 2003, statin uptake and the use of combined drug treatment in elderly men and women increased markedly. Further potential exists, however, for reducing the risk of recurrent coronary heart disease in older patients, particularly by improving the uptake of medication among angina patients, and by more extensive use of blood pressure lowering treatment (particularly with beta blockers and ACE inhibitors).

Adrenergic beta-Antagonists↗
PubMed2006

Associations of vitamin C status, fruit and vegetable intakes, and markers of inflammation and hemostasis.

BACKGROUND: It has been suggested that a high dietary intake and high circulating concentrations of vitamin C may protect against ischemic heart disease. OBJECTIVES: The objective was to examine the associations between dietary and plasma vitamin C concentrations, fruit and vegetable intakes, and markers of inflammation and hemostasis associated with cardiovascular disease in older men free of cardiovascular disease. DESIGN: This cross-sectional study examined 3258 men aged 60-79 y with no physician diagnosis of myocardial infarction, stroke, or diabetes and who were drawn from general practices in 24 British towns. Fruit and vegetable intakes and dietary vitamin C were assessed by using a food-frequency questionnaire. RESULTS: Plasma vitamin C, fruit intake, and dietary vitamin C intake were significantly and inversely associated with mean concentrations of C-reactive protein, an acute phase reactant, and tissue plasminogen activator (t-PA) antigen, a marker of endothelial dysfunction, even after adjustment for confounders. Vegetable intake was correlated significantly (inversely) only with t-PA. For plasma vitamin C (highest versus lowest quartile), the adjusted odds of elevated C-reactive protein and t-PA (highest tertile versus lowest tertile) were 0.56 (95% CI: 0.44, 0.71) and 0.79 (0.62, 1.00); for fruit intake, the corresponding odds ratios were 0.76 (0.60, 0.95) and 0.76 (0.61, 0.95). Plasma (but not dietary) vitamin C also showed inverse associations with both fibrinogen concentrations and blood viscosity. No associations were seen with von Willebrand factor or factor VIII. CONCLUSION: The findings suggest that vitamin C has antiinflammatory effects and is associated with lower endothelial dysfunction in men with no history of cardiovascular disease or diabetes.

Acute-Phase Proteins↗
PubMed2006

Does breastfeeding influence risk of type 2 diabetes in later life? A quantitative analysis of published evidence.

BACKGROUND: Observational evidence suggests that having been breastfed in infancy may reduce the prevalence of type 2 diabetes in later life. OBJECTIVE: The objective was to examine the influence of initial breastfeeding on type 2 diabetes and blood glucose and insulin concentrations. DESIGN: A systematic review of published studies identified 1010 reports; 23 examined the relation between infant feeding and type 2 diabetes in later life or risk factors for diabetes. Risk factors in infants were examined separately from those in children and adults. All estimates were pooled by using fixed-effect models; differences <0 and ratios <1 imply a beneficial effect of breastfeeding. RESULTS: Subjects who were breastfed had a lower risk of type 2 diabetes in later life than did those who were formula fed (7 studies; 76 744 subjects; odds ratio: 0.61; 95% CI: 0.44, 0.85; P = 0.003). Children and adults without diabetes who had been breastfed had marginally lower fasting insulin concentrations than did those who were formula fed (6 studies; 4800 subjects; percentage difference: -3%; 95% CI: -8%, 1%; P = 0.13); no significant difference in fasting glucose concentrations was observed. Breastfed infants had lower mean preprandial blood glucose (12 studies; 560 subjects; mean difference: -0.17 mmol/L; 95% CI: -0.28, -0.05 mmol/L; P = 0.005) and insulin (7 studies; 291 subjects; mean difference: -2.86 pmol/L; 95% CI: -5.76, 0.04 pmol/L; P = 0.054) concentrations than did those who were formula fed. CONCLUSION: Breastfeeding in infancy is associated with a reduced risk of type 2 diabetes, with marginally lower insulin concentrations in later life, and with lower blood glucose and serum insulin concentrations in infancy.

Adolescent↗
PubMed2006

A study of TH01 and IGF2-INS-TH haplotypes in relation to smoking initiation in three independent surveys.

OBJECTIVES: Recent studies suggest an association between a microsatellite locus (TH01) located in intron 1 of the tyrosine hydroxylase gene (TH) and nicotine dependence. We aimed here to study whether both TH01 and haplotypes of the wider IGF2-INS-TH region influence initiation of regular smoking in current smokers. METHODS: A total of 3637 individuals from three independent studies (two of adults and one of adolescents) were analysed in relation to the age of first regular smoking (AFRS). Haplotypes and genotypes were obtained for the polymorphisms TH01, IGF2 ApaI, INS HphI and DRD4 VNTR (48 bp)n. Association between IGF2-INS-TH haplotypes and AFRS was tested by a regression model. A genotype-based genetic model assuming additivity was followed in order to estimate the effect of individual loci. RESULTS: Overall, no significant associations were found after correcting for multiple tests. However, an IGF2-INS-TH haplotype (*5) was found to be nominally associated with AFRS at younger ages in adult smokers. Analyses of individual loci points to TH01 as a possible candidate influencing initiation of regular smoking. An AFRS-lowering trend nominally associated with allele 9 in a dosage-dependent manner was identified in both adult cohorts. TH01 did not show association or trend with age of initiation (first puff) either in adolescents or in the adolescents smoking regularly at age 18. CONCLUSION: This study adds to the genetic evaluation of the associations of TH01 with smoking predisposition. Differences between historical and prospective surveys, different biological pathways and possible functional roles of this microsatellite in smoking initiation are discussed.

Genetic Predisposition to Disease↗
PubMed2006

Age at puberty and adult blood pressure and body size in a British birth cohort study.

OBJECTIVE: To investigate the association between age at puberty and blood pressure at age 53 years. DESIGN: A prospective birth cohort study with regular contacts through childhood and adulthood until the age of 53 years. PARTICIPANTS: A total of 1193 men and 1204 women, from a sample of 5362 born in Britain in March 1946. MAIN OUTCOME MEASURE: Blood pressure at age 53 years. RESULTS: Regression models indicated that men who had reached puberty latest had a lower mean systolic blood pressure (SBP; P = 0.03) and diastolic blood pressure (DBP; P = 0.01) at 53 years than others. The mean SBP (95% confidence interval) was 6.4 mmHg (1.8, 10.9) greater in the earliest puberty group compared with the latest; for DBP the difference was 4.6 mmHg (1.9, 7.4). The associations were not accounted for by current body size, even though later puberty was associated with a decreasing body mass index (BMI) at 53 years. Neither were they accounted for by prepubertal body size, birth weight, or childhood and adult social class. Although women who reached puberty early had a higher BMI and shorter stature at 53 years compared with other women, they did not have higher blood pressure. CONCLUSIONS: Better health behaviours in men reaching puberty late may explain the association between age at puberty and blood pressure. Alternatively, age at puberty may be a marker of the whole growth trajectory, distinguishing characteristics important in the later development of high blood pressure. The association of early puberty with high adult BMI in both sexes highlights the importance of controlling obesity in those who mature early.

Aging↗
PubMed2006

Modifiable lifestyle factors and the metabolic syndrome in older men: Effects of lifestyle changes.

OBJECTIVES: To examine the influence of lifestyle factors and changes in these factors on risk of the metabolic syndrome in elderly men. DESIGN: Cross-sectional and longitudinal analyses of cohort study. SETTING: General practices in 24 British towns. PARTICIPANTS: Three thousand fifty-one men aged 60 to 79 with no diabetes mellitus or diagnosis of coronary heart disease. MEASUREMENTS: Lifestyle factors (smoking, physical activity, alcohol intake, body weight, dietary fat and carbohydrate intake) including recent changes in the previous 3 years (physical activity and body weight); metabolic syndrome. RESULTS: After adjustment for each of the other modifiable lifestyle factors, overweight/obesity and physical inactivity were associated with a significantly higher risk of the metabolic syndrome, as were cigarette smoking and a high-carbohydrate diet (>57% of energy). Alcohol intake and dietary fat intake were not related to the metabolic syndrome. Long-term ex-smokers showed similar risk to never smokers. Taking up physical activity and losing weight in the previous 3 years were associated with a reduction in risk of the metabolic syndrome. CONCLUSION: Overweight/obesity, physical inactivity, a high-carbohydrate diet, and cigarette smoking are associated with higher risk of the metabolic syndrome in elderly men. Modification of lifestyle factors, even later in life, has considerable potential for primary prevention of the metabolic syndrome.

Aged↗
PubMed2005

Secondary prevention of coronary heart disease in older British men: extent of inequalities before and after implementation of the National Service Framework.

BACKGROUND: Deficiencies in implementation of secondary prevention of coronary heart disease (CHD) have been identified. We explored the extent of medication use for secondary prevention of CHD since the introduction of the National Service Framework (NSF) for CHD and the influence of patient age, social class, region and time since diagnosis in older British men. METHODS: Prospective study in 24 British towns using patient information on medication use in 1998-2000 and 2003. Subjects were men with medically recorded diagnosis of myocardial infarction or angina, aged 62-85 years in 2003. Prevalence of medication use (aspirin, statins, angiotensin-converting enzyme (ACE) inhibitors and beta-blockers) in 1998-2000 and 2003 was ascertained. RESULTS: Prevalence of use of all drugs increased in 2003 and was markedly higher in patients with a history of myocardial infarction than angina. Older age was related to lower prevalence of drug use, particularly statins. In 2000, older subjects (74-85 years) were 60% [95% confidence interval (CI) = 41-72 per cent] less likely to receive statins compared with younger subjects (62-73 years); this pattern changed very little between 2000 and 2003. Although social class appeared to have little relation to drug use, the prevalence of use of all medications decreased with increasing time since diagnosis. CONCLUSIONS: Although the uptake of medications for secondary prevention in CHD patients increased since the NSF in 2000, marked age inequalities in statin use were present both in 1998-2000 and 2003. Further action is needed to reduce these inequalities, because older patients are at particularly high risk of recurrent and fatal CHD.

Aged↗
PubMed2005

Sex differences in the association between birth weight and total cholesterol. A meta-analysis.

PURPOSE: Determine whether a sex difference exists in the association between birth weight and total cholesterol later in life. METHODS: Meta-analysis of within-study differences in regression coefficients of cholesterol on birth weight. RESULTS: A total of 34 regression coefficients from 30 studies were included in the analyses; these provided data on 33,650 males and 23,129 females. There was evidence that the inverse association between birth weight and total cholesterol was stronger in males compared to females. The pooled within-study difference in age-adjusted regression coefficients was -0.03 mmol/l (-0.06, -0.01), p = 0.02 and the pooled within-study difference in age and body mass index adjusted regression coefficients was -0.04 mmol/l (-0.07, -0.02), p = 0.002. There was no evidence of heterogeneity in these meta-analyses (both p values > 0.6). CONCLUSIONS: These results provide some evidence for a sex difference in the birth weight-total cholesterol association. This is consistent with studies of fetal growth which suggest that birth size reflects different biological processes for females and males. However, other very large studies are required to confirm this finding.

Adolescent↗
PubMed2005

Trends in rates of different forms of diagnosed coronary heart disease, 1978 to 2000: prospective, population based study of British men.

OBJECTIVE: To examine trends over time in rates of different forms of diagnosed coronary heart disease among British men, during a period in which mortality due to coronary heart disease has been declining. DESIGN: Prospective cohort study covering the period 1978-80 to 1998-2000. PARTICIPANTS: 7735 men, aged 40-59 at entry, randomly selected from one general practice in each of 24 British towns. MAIN OUTCOME MEASURES: Trends in the rates of major coronary events, first diagnosed angina and first diagnosed coronary heart disease (any fatal or non-fatal documented event or diagnosis). Events were ascertained from NHS central registers and reviews of medical records from general practices. RESULTS: Over the 20 year period, 1561 major coronary events occurred; 1087 and 1816 men had new diagnoses of angina and coronary heart disease, respectively. The age adjusted annual relative changes were -3.6% (95% confidence interval -4.8% to -2.4%, P < 0.001) for all major coronary events, 2.6% (1.1% to 4.0%, P < 0.001) for first diagnosed angina and -0.8% (-1.8% to 0.3%, P = 0.18) for first diagnosed coronary heart disease. The fall in major coronary events occurred across all categories of event (fatal and non-fatal, first and recurrent). Similarly, first diagnosed angina increased for both uncomplicated angina and angina after myocardial infarction. The age adjusted annual relative change in case fatality at 28 days of first major coronary events was -1.4% (-3.1% to 0.4%, P = 0.12). CONCLUSIONS: Among British middle aged men, a substantial decline in the rate of major coronary events over the past two decades seems to have been largely offset by an increase in the incidence of diagnosed angina. Overall there was little change in the incidence of first diagnosed coronary heart disease. A continuing need exists for resources and services for coronary heart disease in general, and for new angina in particular.

Adult↗
PubMed2005

Lifestyle and cardiovascular disease in middle-aged British men: the effect of adjusting for within-person variation.

AIMS: To examine the effect that within-person variation has on the estimated risk associations between cigarette smoking, physical inactivity, and increased body mass index (BMI) and the development of cardiovascular disease (CVD) in middle-aged British men. METHODS AND RESULTS: In total, 6452 men aged 40-59 with no prior evidence of CVD were followed for major CVD events (fatal/non-fatal myocardial infarction or stroke) and all-cause mortality over 20 years; lifestyle characteristics were ascertained at regular points throughout the study. A major CVD event within the first 20 years was observed in 1194 men (18.5%). Use of baseline assessments of cigarette smoking and physical activity in analyses resulted in underestimation of the associations between average cumulative exposure to these factors and major CVD risk. After correction for within-person variation, major CVD rates were over four times higher for heavy smokers (> or =40 cigarettes/day) compared with never smokers and three times higher for physically inactive men compared with moderately active men. Major CVD risk increased by 6% for each 1 kg/m(2) increase in usual BMI. If all men had experienced the risk levels of the men who had never regularly smoked cigarettes, were moderately active, and had a BMI of < or =25 kg/m(2) (6% of the population), 66% of the observed major CVD events would have been prevented or postponed (63% before adjustment for within-person variation). Adjustment for a range of other risk factors had little effect on the results. Similar results were obtained for all-cause mortality. CONCLUSION: Failure to take account of within-person variation can lead to underestimation of the importance of lifestyle characteristics in determining CVD risk. Primary prevention through lifestyle modification has a great preventive potential.

Body Mass Index↗
PubMed2005

Associations between cigarette smoking, pipe/cigar smoking, and smoking cessation, and haemostatic and inflammatory markers for cardiovascular disease.

AIMS: To examine the associations between cigarette smoking, pipe/cigar smoking, and years since quitting smoking, and inflammatory and haemostatic markers. METHODS AND RESULTS: A study in 2920 men aged 60-79 with no history of myocardial infarction, angina, stroke, or diabetes, and who were not on warfarin, from general practices in 24 British towns. After adjustment for other major cardiovascular risk factors, compared with never smokers, current cigarette smokers showed significantly higher levels of C-reactive protein (2.53 vs. 1.35 mg/L), white cell count (7.92 vs. 6.42 x 10(9)/L), and fibrinogen (3.51 vs. 3.13 g/L). They also showed higher levels of haematocrit, blood and plasma viscosity, tissue plasminogen activator antigen, and fibrin D-dimer, and lower levels of albumin. Primary pipe/cigar smokers showed levels similar to never smokers. Ex-cigarette smokers and secondary pipe/cigar smokers showed intermediate levels although secondary pipe/cigar smokers showed higher odds of having elevated white cell count and fibrinogen than ex-cigarette smokers. Most inflammatory and haemostatic levels improved within 5 years of smoking cessation but took over 20 years to revert to levels of never smokers. CONCLUSION: These findings suggest that activation of inflammation and haemostasis may be potential mechanisms by which cigarette and pipe/cigar smoking increase cardiovascular risk.

Adult↗
PubMed2005

Are early life factors responsible for international differences in adult blood pressure? An ecological study.

BACKGROUND: Although low birthweight has been related to higher mean blood pressure in individuals, there have been very few studies on the contribution of the 'fetal origins hypothesis' to international variations in mean blood pressure. METHODS: Standardized data on mean blood pressure levels in adults aged 20-29 years (available from the INTERSALT study countries) were related to data on mean birthweight and infant mortality rates (IMRs) approximately 25 years earlier (available from the World Health Organization and the United Nations statistics for 24 of these countries). RESULTS: Population mean systolic pressure was inversely correlated with IMR (r = -0.66, P < 0.001) and positively correlated with mean birthweight (r = 0.36, P = 0.108). These correlations were little affected by adjustment either for current body mass index or for current sodium, potassium, and alcohol intake. CONCLUSIONS: The directions of these associations suggest that low mean birthweight and high infant mortality are not important determinants of high population mean adult blood pressure levels.

Adult↗
PubMed2005

The metabolic syndrome and insulin resistance: relationship to haemostatic and inflammatory markers in older non-diabetic men.

AIMS: We have examined the cross-sectional relationship between insulin resistance, the metabolic syndrome and haemostatic and inflammatory markers. METHODS AND RESULTS: We carried out the study in 2722 non-diabetic men aged 60-79 years with no history of coronary heart disease or stroke and who were not on warfarin treatment, drawn from general practices in 24 British towns. Insulin resistance (HOMA) was significantly associated with increased inflammatory markers (C-reactive protein (CRP), white cell count), coagulation factors VII-IX, von Willebrand factor (VWF) and tissue plasminogen activator (t-PA) antigens (markers of endothelial dysfunction) and blood viscosity after adjustment for age, smoking, physical activity, alcohol intake and waist circumference. Relationships with fibrinogen and fibrin D-dimer were weak. The relationship between HOMA and CRP was abolished after adjustment for t-PA. The prevalence of the metabolic syndrome was similar using World Health Organization (WHO) and National Cholesterol Education Program definitions (26.7% and 27.0%) but associations between the metabolic syndrome and increased haemostatic markers, particularly for raised factor VIII and VWF were stronger using WHO criteria. CONCLUSION: Insulin resistance and the metabolic syndrome showed significant associations with markers of haemostasis and inflammation, which may be relevant to their associations with cardiovascular disease.

Aged↗