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ABSTRACT: Changes and variation in retinal vessel width are related to vascular risk factors and prospectively related to cardiovascular disease in later life. Hence, assessment of vessel width may be a useful physio-marker and potential predictor of cardiovascular status. However, measurement of vessel calibre from retinal images is a challenging process to automate. This paper proposes an automated system to measure vessel calibre in retinal images, which is demonstrated in images of multi-ethnic school children. The diameter measurement is based on the detection of the centreline pixels from a vessel probability map image, determining the vessel orientation at these pixels, extracting the vessel segments and later using a two-dimensional model, which is optimized to fit various types of intensity profiles of vessel segments. The width is then estimated from parameters of the optimized model. The method is also quantitatively analyzed using monochromatic representations of different colour spaces. The algorithm is evaluated on a recently introduced public database CHASE_DB1, which is a subset of retinal images of multi-ethnic children from the Child Heart and Health Study in England (CHASE) dataset. Moreover, the precise estimation of retinal vascular widths is critical for epidemiologists to identify the risk factors. This work also introduces an interactive software tool for epidemiologists, with which retinal vessel calibre can be precisely marked.
Computerized medical imaging and graphics: the official journal of the Computerized Medical Imaging Society 01/2013; 37(1):48-60. · 1.04 Impact Factor
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Diabetologia 04/2012; 48(7):1429-1429. · 6.81 Impact Factor
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ABSTRACT: In England and Wales, approximately 20% extra deaths from coronary heart disease (CHD) occur between December and March, among older people. Circulating concentrations of tissue plasminogen activator (t-PA), von Willebrand factor (VWF) and fibrin D-dimer are associated with arterial disease, and tend to peak in winter. The potential contributions of these hemostatic activation measures to excess winter mortality are unknown.
To estimate contributions of hemostatic factors to excess winter mortality.
Seasonal patterns in t-PA, VWF and D-dimer were investigated in 4088 men aged 60-79 years from 24 British towns. Data on established coronary risk factors were collected by questionnaire, physical examination and blood sampling. The adjusted mean increase in hemostatic markers during winter months, after adjustment for a range of coronary risk factors, was combined with associations of each marker with CHD mortality obtained from 9 years' follow-up of participants, to predict degree of excess CHD winter mortality. Associations of hemostatic markers with CHD incidence from large meta-analyses were also used.
All three markers showed peaks in winter; the adjusted mean increases during winter months were 0.21, 0.15 and 0.12 standard deviations for t-PA, VWF and log(D-dimer), respectively. Predicted excess hazard ratios for winter CHD mortality were 3.0%, 2.4% and 3.1%, respectively, in combination, representing an 8.6% excess. This increased to 14% when applying meta-analysis estimates.
Seasonal patterns in three hemostatic markers predict at least 8.6% excess CHD mortality in winter in Great Britain, potentially accounting for over half the excess observed in recent years.
Journal of Thrombosis and Haemostasis 03/2012; 10(3):352-8. · 5.73 Impact Factor
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ABSTRACT: Circulating levels of C-reactive protein (CRP), fibrinogen, fibrin D-dimer, tissue plasminogen activator antigen (t-PA) and von Willebrand factor (VWF) are associated with incident coronary heart disease (CHD). However, their associations with metabolic syndrome and its components in large populations of men and women have not been well defined.
We compare the sex associations of these biomarkers with established CHD risk factors, metabolic syndrome and its components in a large cohort. Patients and Methods: 8302 men and women aged 45 years from the British 1958 birth cohort provided a blood sample. Analyses were restricted to 3457 men and 3464 women with complete data on all risk factors and no history of cardiovascular disease. Multiple regression analyses adjusted for smoking, social class, alcohol consumption and variables related to biomarker measurement error.
Adjusted sex differences in levels of all biomarkers (except VWF) varied according to presence/absence of metabolic syndrome, its components and obesity (BMI ≥30 kg m(-) (2)). Associations in women were up to twice as strong for CRP, fibrinogen and t-PA with markers of obesity (body mass index, waist circumference), blood pressure, blood lipids and metabolic syndrome. D-dimer showed weaker associations and less heterogeneity by sex. There was no evidence of sex interaction in associations with VWF.
Associations between CRP, fibrinogen and t-PA and metabolic syndrome and its components were stronger in women than in men. Understanding the reasons for these differences across sex will be important in understanding the pathophysiology of cardiovascular and metabolic disease in men and women.
Journal of Thrombosis and Haemostasis 09/2011; 9(12):2337-44. · 5.73 Impact Factor
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ABSTRACT: 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.
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.
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.
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.
Diabetologia 08/2011; 55(1):80-7. · 6.81 Impact Factor
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ABSTRACT: CD40 ligand(CD40L) is implicated in atherosclerotic plaque formation.
We investigated prospective associations between circulating soluble CD40L and myocardial infraction (MI) or stroke in an older general population cohort, accounting for established and novel cardiovascular risk factors.
Baseline serum CD40L (sCD40L) was measured in incident MI (n = 368) and stroke (n = 304) cases and two controls per case, 'nested' in prospective UK studies of 4252 men and 4286 women aged 60-79 years, sampled from general practices in Britain in 1998-2000, with 7-year follow-up for fatal and non-fatal MI and stroke.
sCD40L was higher in smokers and negatively associated with lung function and positively associated with total cholesterol and markers of inflammation, but not with other established cardiovascular disease (CVD) risk factors. Geometric mean sCD40L levels did not differ between MI cases and controls (5.94 ng mL(-1) vs. 5.82 ng mL(-1); P = 0.5) or between stroke cases and controls (5.61 ng mL(-1) vs. 5.28 ng mL(-1), P = 0.1). There was no strong evidence for elevated risk of MI or stroke in multivariable models comparing participants in the top to those in the bottom third of sCD40L. Age-adjusted odds ratios (ORs) were 1.39 [95% confidence interval (CI) 0.98, 1.96] for MI and 1.16 (0.78, 1.73) for stroke. These attenuated to 1.24 (95% CI 0.86, 1.79) and 1.18 (0.78, 1.78), respectively, after adjustment for established and novel CVD risk factors.
sCD40L is associated with other inflammatory markers but is not itself a strong independent risk marker for either stroke or MI.
Journal of Thrombosis and Haemostasis 06/2011; 9(8):1452-9. · 5.73 Impact Factor
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ABSTRACT: To develop strategies based on simple clinical assessment and blood markers to identify older individuals at high risk for Type 2 diabetes.
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.
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.
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.
Diabetic Medicine 01/2011; 28(1):23-30. · 2.90 Impact Factor
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ABSTRACT: To examine trends in initiation and continuation of statin treatment after myocardial infarction (MI) and their determinants, during a period of increasing usage.
9367 patients aged 30-84 with a first Myocardial Infarction (MI) in 1997-2006 were identified in DIN-LINK, an anonymised, UK primary care database. We assessed statin initiation (prescription within 6 months of MI) and continued therapy (% covered by a prescription on a given day of those prescribed a statin within 6 months). The influences of co-morbidities and socio-economic deprivation (Index of Multiple Deprivation) were examined. Statin initiation increased from 37% for MIs in 1997 to 92% in 2006. Continuation at 1 year remained stable over successive cohorts at approximately 80%, settling to about 76% in patients with 5-10 years follow up. Younger age, affluence, revascularisation in 6 months after MI, and absence of congestive heart failure, predicted higher initiation and continuation; a diagnosis of hypertension or diabetes predicted higher initiation, while smoking was associated with poorer continuation. Men had higher initiation and continued therapy, but these effects were largely explained by their younger age. Type of statin initially prescribed did not influence continued usage.
Statin use after MI increased markedly between 1997 and 2006, whilst continued therapy remained high and stable. Importantly, first choice of statin had no effect on continuation. Whilst the high current levels of initiation may have reached a ceiling, increasing continuation rates among smokers, older patients and those from lower socio-economic groups, should remain a priority.
Nutrition, metabolism, and cardiovascular diseases: NMCD 12/2010; 22(5):400-8. · 3.52 Impact Factor
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ABSTRACT: To examine whether second-hand smoke (SHS) exposure measured by serum cotinine is associated with increased coronary heart disease (CHD) and stroke risk among contemporary older British adults.
Prospective population-based study with self-reported medical history and health behaviours. Fasting blood samples were analysed for serum cotinine and cardiovascular disease (CVD) risk markers.
Primary care centres in 25 British towns in 1998-2001.
8512 60-79-year-old men and women selected from primary care registers.
Fatal and non-fatal myocardial infarction (MI; n=445) and stroke (n=386) during median 7.8-year follow-up.
Observational study of serum cotinine assayed from fasting blood sample using liquid chromatography tandem mass spectrometry method, and self-reported smoking history.
Among 5374 non-smokers without pre-existing CVD, geometric mean cotinine was 0.15 ng/ml (IQR 0.05-0.30). Compared with non-smokers with cotinine < or =0.05 ng/ml, higher cotinine levels (0.06-0.19, 0.2-0.7 and 0.71-15.0 ng/ml) showed little association with MI; adjusted HRs were 0.92 (95% CI 0.63 to 1.35), 1.07 (0.73 to 1.55) and 1.09 (0.69 to 1.72), p(trend)=0.69. Equivalent HRs for stroke were 0.82 (0.55 to 1.23), 0.74 (0.48 to 1.13) and 0.69 (0.41 to 1.17), p(trend)=0.065. The adjustment for sociodemographic, behavioural and CVD risk factors had little effect on the results. The HR of MI for smokers (1-9 cigarettes/day) compared with non-smokers with cotinine < or =0.05 ng/ml was 2.14 (1.39 to 3.52) and 1.03 (0.52 to 2.04) for stroke.
In contemporary older men and women, SHS exposure (predominantly at low levels) was not related to CHD or stroke risks, but we cannot rule out the possibility of modest effects at higher exposure levels.
Heart (British Cardiac Society) 06/2010; 96(11):854-9. · 4.22 Impact Factor
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ABSTRACT: Physical inactivity is implicated in unfavourable patterns of obesity and cardiometabolic risk in childhood. However, few studies have quantified these associations using objective physical activity measurements in children from different ethnic groups. We examined these associations in UK children of South Asian, black African-Caribbean and white European origin.
This was a cross-sectional study of 2,049 primary school children in three UK cities, who had standardised anthropometric measurements, provided fasting blood samples and wore activity monitors for up to 7 days. Data were analysed using multilevel linear regression and allowing for measurement error.
Overall physical activity levels showed strong inverse graded associations with adiposity markers (particularly sum of skinfold thicknesses), fasting insulin, HOMA insulin resistance, triacylglycerol and C-reactive protein; for an increase of 100 counts of physical activity per min of registered time, levels of these factors were 12.2% (95% CI 10.2-14.1%), 10.2% (95% CI 7.5-12.8%), 10.2% (95% CI 7.5-12.8%), 5.8% (95% CI 4.0-7.5%) and 19.2% (95% CI 13.9-24.2%) lower, respectively. Similar increments in physical activity levels were associated with lower diastolic blood pressure (1.0 mmHg, 95% CI 0.6-1.5 mmHg) and LDL-cholesterol (0.04 mmol/l, 95% CI 0.01-0.07 mmol/l), and higher HDL-cholesterol (0.02 mmol/l, 95% CI 0.01-0.04 mmol/l). Moreover, associations were broadly similar in strength in all ethnic groups. All associations between physical activity and cardiometabolic risk factors were reduced (albeit variably) after adjustment for adiposity.
Objectively measured physical activity correlates at least as well with obesity and cardiometabolic risk factors in South Asian and African-Caribbean children as in white European children, suggesting that efforts to increase activity levels in such groups would have equally beneficial effects.
Diabetologia 05/2010; 53(8):1620-30. · 6.81 Impact Factor
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ABSTRACT: In the UK, South Asian adults have increased risks of CHD, type 2 diabetes and central obesity. Black African-Caribbeans, in contrast, have increased risks of type 2 diabetes and general obesity but lower CHD risk. There is growing evidence that these risk differences emerge in early life and that nutritional factors may be important. We have therefore examined the variations in nutritional composition of the diets of South Asian, black African-Caribbean and white European children, using 24 h recalls of dietary intake collected during a cross-sectional survey of cardiovascular health in eighty-five primary schools in London, Birmingham and Leicester. In all, 2209 children aged 9-10 years took part, including 558 of South Asian, 560 of black African-Caribbean and 543 of white European ethnicity. Compared with white Europeans, South Asian children reported higher mean total energy intake; their intakes of total fat, polyunsaturated fat and protein (both absolute and as proportions of total energy intake) were higher and their intakes of carbohydrate as a proportion of energy (particularly sugars), vitamin C and D, Ca and haem Fe were lower. These differences were especially marked for Bangladeshi children. Black African-Caribbean children had lower intakes of total and saturated fat (both absolute and as proportions of energy intake), NSP, vitamin D and Ca. The lower total and saturated fat intakes were particularly marked among black African children. Appreciable ethnic differences exist in the nutritional composition of children's diets, which may contribute to future differences in chronic disease risk.
The British journal of nutrition 03/2010; 104(2):276-85. · 3.45 Impact Factor
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ABSTRACT: 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.
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.
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.
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.
Diabetologia 02/2010; 53(5):890-8. · 6.81 Impact Factor
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ABSTRACT: 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.
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.
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.
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.
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.
Journal of Thrombosis and Haemostasis 11/2009; 7(11):1779-86. · 5.73 Impact Factor
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ABSTRACT: The prevalence of Type 2 diabetes is increasing worldwide; predictions suggest that the disease will reach epidemic proportions this century. This study aims to estimate the extent of the increase in prevalence of diagnosed Type 2 diabetes in British men between 1978 and 2005.
A representative cohort of 7722 British men aged 40-59 years at entry in 1978-1980 were selected from general practices in 24 British towns. Seven sequential questionnaire surveys were carried out between 1978 and 2005, recording recall of a doctor diagnosis of diabetes at each time point. Logistic regression models with generalized estimating equations were fitted to provide age-adjusted estimates of the calendar year increases in odds of Type 2 diabetes, both overall and for consecutive periods, each of approximately 5 years.
The crude prevalence of Type 2 diabetes increased from 1.2% in 1978-1980 to 12.1% in 2005. The age-adjusted average annual increase in Type 2 diabetes prevalence for the 27-year study period was 7.0% [95% confidence interval (CI) 5.4%, 8.6%]. However, the age-adjusted annual rate of increase increased over time, from 4.3% (95% CI 0.4%, 8.2%) between 1979 and 1984 to 11.8% (95% CI 8.4%, 15.4%) between 2003 and 2005; P (trend) = 0.01. The highest annual increases occurred in subjects with higher mean body mass index levels and in towns in Scotland.
The prevalence of Type 2 diabetes has risen substantially in Britain during the last three decades; the recent rate of increase has been almost three times greater than that in the early 1980s.
Diabetic Medicine 09/2009; 26(8):766-72. · 2.90 Impact Factor
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ABSTRACT: The extent to which hemostatic and inflammatory biomarkers are related to angina pectoris as compared with myocardial infarction (MI) remains uncertain. We examined the relationship between a wide range of inflammatory and hemostatic biomarkers, including markers of activated coagulation, fibrinolysis and endothelial dysfunction and viscosity, with incident myocardial infarction (MI) or coronary heart disease (CHD) death and incident angina pectoris uncomplicated by MI or CHD death in older men.
A prospective study of 3217 men aged 60-79 years with no baseline CHD (angina or MI) and who were not on warfarin, followed up for 7 years during which there were 198 MI/CHD death cases and 220 incident uncomplicated angina cases.
Inflammatory biomarkers [C-reactive protein (CRP), interleukin-6, fibrinogen], plasma viscosity and hemostatic biomarkers [von Willebrand factor (VWF) and fibrin D-dimer] were associated with a significant increased risk of MI/CHD death but not with uncomplicated angina even after adjustment for age and conventional risk factors. Adjustment for CRP attenuated the relationships between VWF, fibrin D-dimer and plasma viscosity with MI/CHD death. Comparisons of differing associations with risk of MI/CHD deaths and uncomplicated angina were significant for the inflammatory markers (P < 0.05) and marginally significant for fibrin D-dimer (P = 0.05). In contrast, established risk factors including blood pressure and high-density lipoprotein (HDL)-cholesterol were associated with both MI/CHD death and uncomplicated angina.
Circulating biomarkers of inflammation and hemostasis are associated with incident MI/CHD death but not incident angina uncomplicated by MI or CHD death in older men.
Journal of Thrombosis and Haemostasis 09/2009; 7(10):1605-11. · 5.73 Impact Factor
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B J Jefferis,
G D O Lowe,
P Welsh,
A Rumley,
D A Lawlor,
S Ebrahim,
C Carson,
M Doig,
C Feyerabend,
L McMeekin,
S G Wannamethee,
D G Cook, P H Whincup
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ABSTRACT: Secondhand smoke (SHS) exposure is associated with elevated CHD risks. Yet the pathways through which this may operate have not been investigated in epidemiologic studies with objective SHS exposure measures and a wide range of CHD risk factors associated with active smoking. Therefore we investigate associations between SHS exposure and CHD risk factors, to clarify how SHS exposure may raise risk of CHD.
Cross-sectional population-based study of 5029 men and women aged 59-80 years from primary care practices in Great Britain. Smoking, behavioural and demographic information was reported in questionnaires; nurses made physical measurements and took blood samples for analysis of serum cotinine and markers of inflammation, hemostasis and endothelial dysfunction.
Active cigarette smokers had lower albumin and higher triglycerides, CRP, IL-6, white cell count, fibrinogen, blood viscosity, factor VIII, VWF and t-PA than non-smokers. Among non-smokers, serum cotinine levels were independently positively associated with CRP, fibrinogen, factor VIII, VWF and t-PA and inversely associated with albumin, after adjustment for age, gender, social and behavioural factors. The differences in CRP, fibrinogen and albumin between cotinine < or =0.05 and >0.7 ng/ml were one-third to one half the size of differences between cotinine < or =0.05 ng/ml and current smokers, but were of similar magnitude for VWF and t-PA.
Endothelial, inflammatory and haemostatic markers related to CHD risk showed independent associations with SHS exposure in the same direction as those for active smoking. Results aid understanding of the associations between SHS exposure and elevated CHD risks.
Atherosclerosis 07/2009; 208(2):550-6. · 3.79 Impact Factor
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ABSTRACT: Although obesity beginning early in life is becoming more common, its implications for coronary heart disease (CHD) risk in later life remain uncertain. We examined the relationship of body mass index (BMI) before 30 years of age to CHD risk in later life.
Systematic review of published studies relating BMI between age 2 and 30 years to later CHD risk. Studies were identified using Medline (1950 onwards), Embase (1980 onwards) and Web of Science (1970 onwards) databases (to November 2007).
Relative risks (RR) of CHD associated with a 1 standard deviation (s.d.) higher BMI (most based on a narrow age range at measurement) were extracted by two authors independently, and combined using random-effect models.
A total of 15 studies provided 17 estimates (731 337 participants, 23 894 CHD events) of the association of early BMI to later CHD outcome. BMI in early childhood (2-6 years, 3 estimates) showed a weak inverse association with CHD risk (RR 0.94, 95% CI 0.82-1.07). BMI in later childhood (7 to <18 years, 7 estimates) and BMI in early adult life (18-30 years, 7 estimates) were both positively related to later CHD risk (RR 1.09, 95% CI 1.00-1.20; RR 1.19, 95% CI 1.11-1.29 respectively). However, there was considerable statistical heterogeneity between study estimates. Results were unaffected by adjustment for social class and/or cigarette smoking, blood pressure and/or total cholesterol, in studies with available data. Gender and year of birth (1900-1976) had little effect on the association.
BMI is positively related to CHD risk from childhood onwards; the associations in young adults are consistent with those observed in middle age. Long-term control of BMI from childhood may be important to reduce the risk of CHD.
International journal of obesity (2005) 06/2009; 33(8):866-77. · 4.34 Impact Factor
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ABSTRACT: The 2004 UK Quality and Outcomes Framework (QOF) remunerates general practitioners for achieving a target blood pressure (BP) of <or=150/90 mm Hg for patients with ischaemic heart disease, stroke and hypertension. Using the DIN-LINK GP database, we investigated whether introducing the target altered BP recording. We extracted 3 164 189 BP measurements from 236 467 patients, with the above diagnoses from 2000 to 2005. Treatment was assessed by Read codes indicating prescriptions for antihypertensive drugs. Over this period, recorded systolic BP (SBP) fell: 36% had an SBP >150 mm Hg in 2000-2001, and only 19% in 2004-2005. However, there was a trend towards recording systolic values just below, rather than just above the 150 cut-off. In 2000-2001, 2.3% of patients had 148-149 recorded and 1.8% had 151-152. In 2004-2005, the figures were 4.2 and 1.3%, respectively. By smoothing the distribution we estimate that the true percentage of patients with SBP>150 mm Hg in 2004-2005 was 23%, rather than the 19% recorded. Moreover, patients with a recorded SBP=148-149 were more likely to have a recorded diastolic BP<or=90 (93%) than patients with SBP=151-152 (78%). However, patients just below the 150 mm Hg cut-off received more antihypertensive treatment than those just above it (odds ratio=1.20, 95% confidence interval 1.01-1.41). We conclude that blood pressure levels in UK primary care have continued to fall through the introduction of QOF, offering significant public health benefits in the future. This fall has been exaggerated due to values being clustered just below the QOF target, but there is no evidence of adverse effects of this on clinical management.
Journal of human hypertension 03/2009; 23(11):764-70. · 2.80 Impact Factor
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ABSTRACT: 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.
To determine whether circulating levels of serum MMP-9 are prospectively related to the risk of CHD in the general population.
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).
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).
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.
QJM: monthly journal of the Association of Physicians 09/2008; 101(10):785-91. · 2.33 Impact Factor
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ABSTRACT: To examine trends and demographic factors affecting persistence with ocular hypotensive therapy, from a period before prostaglandins were available to when they were the most common therapy.
Computerised patient records from 94 general practices across the United Kingdom, identified 5670 registered patients newly prescribed an ocular hypotensive drug (1993-2005). Persistence was defined as continuing therapy without a 90-day gap in prescription for (i) any ocular hypotensive and (ii) initial monotherapy. Time to failure with the treatment was compared using proportional hazard analyses, adjusted for age, gender, practice, year of initial treatment, and a sociodemographic indicator. Study findings were set in the context of a review of the literature.
Percentage persistent at 1-year rose after 1997 when prostaglandins were introduced; from 61% in 1994-1996 to 70% in 2002-2004. Persistence with any treatment did not differ between those initiated on beta-blockers compared to prostaglandins (1.05, 95% CI 0.93-1.17). However, 20% of subjects initiated on beta-blockers received a prostaglandin by 1 year. Conversely, 8% of those initiated on prostaglandins received a beta-blocker. When failure with initial therapy was considered, beta-blockers appeared worse (1.35, 95% CI 1.21-1.50); this was consistent with findings from six studies in the review (1.40, 95% CI 1.34-1.46). Neither gender nor social factors were associated with persistence, but younger subjects (35-64 years) were significantly more likely to fail as were those over 85 years.
Introduction of prostaglandins may explain an improvement in persistence over a decade. However, whether the higher cost of initiating patients on prostaglandins is justified remains questionable unless clinically indicated.
Eye (London, England) 08/2008; 23(5):1098-110. · 1.97 Impact Factor
