Claire Carson

The association between orthostatic hypotension and medication use in the British Women’s Heart and Health Study

OBJECTIVEnto determine the prevalence of orthostatic hypotension (OH) and associations with medication use in community-dwelling older women.nnnDESIGNncross-sectional analysis using data from the British Womens Heart and Health Study.nnnSETTINGngeneral practices in 23 towns in the UK.nnnPARTICIPANTSn3,775 women aged 60-80 years from 1999 to 2001.nnnMAIN OUTCOME MEASUREnorthostatic hypotension-drop of > or =20 mmHg in systolic and/or a drop of > or =10 mmHg in diastolic blood pressure on standing.nnnRESULTSnprevalence of OH was 28% (95% confidence interval [CI] 26.6, 29.4), which increased with age and hypertension. Regardless of treatment status or diagnosed hypertension, raised blood pressure was strongly associated with OH (P < 0.001). OH was strongly associated with number of antihypertensives taken (none vs three or more: odds ratio [OR] 2.24, 95% CI 1.47-3.40, P < 0.001); the association was slightly attenuated after allowing for age and co-morbidities (OR 1.99; 95% CI 1.30, 3.05; P = 0.003). Women with multiple co-morbidities had markedly increased odds of OH independent of age, number and type of medications taken (none vs four or more diagnoses: OR 2.28, 95% CI 1.58-3.30, P = 0.005).nnnCONCLUSIONnuncontrolled hypertension, use of three or more antihypertensives and multiple co-morbidities are predictors of OH in older women. Detection or monitoring of OH in these groups may prevent women from suffering its adverse consequences.

Secondhand smoke (SHS) exposure is associated with circulating markers of inflammation and endothelial function in adult men and women.

Aims 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. Methods 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. Results 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 ≤0.05 and >0.7 ng/ml were one-third to one half the size of differences between cotinine ≤0.05 ng/ml and current smokers, but were of similar magnitude for VWF and t-PA. Conclusions 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.

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

Aims/hypothesisThe 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.MethodsIn this prospective study, non-diabetic men (nu2009=u20093,519) and women (nu2009=u20093,404) aged 60–79xa0years were followed up for 7xa0years. There were 169 and 128 incident cases of type 2 diabetes in men and women, respectively.ResultsBMI, 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 (AUCu2009=u20090.726 and 0.713, respectively); WHR was the weakest predictor (AUCu2009=u20090.656). In women, WC was a significantly stronger predictor (AUCu2009=u20090.780) than either BMI (AUCu2009=u20090.733) or WHR (AUCu2009=u20090.728; pu2009<u20090.01 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 100xa0cm in men and 92xa0cm in women.Conclusions/interpretationIn older men, BMI and WC yielded similar prediction of risk of type 2 diabetes, whereas WC was clearly a superior predictor in older women.

Prospective study of matrix metalloproteinase-9 and risk of myocardial infarction and stroke in older men and women

Objectives The endopeptidase matrix metalloproteinase-9 (MMP-9) is implicated in atherosclerotic plaque rupture. We investigate prospective associations between MMP-9 and MI or stroke in an older general population cohort, accounting for established and novel cardiovascular risk factors. Methods Baseline serum MMP-9 was measured in incident MI (n = 368) and stroke (n = 299) cases and two controls per case, ‘nested’ in prospective 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. Results Geometric mean MMP-9 was 528 ng/mL (IQR 397, 743) in MI cases compared to 501 ng/mL (IQR 370, 743) in controls, p = 0.10. Participants in the top compared to bottom third of MMP-9 levels had an age-adjusted odds ratio for MI of 1.53 (95% CI 1.09, 2.13), which attenuated to 1.18 (95% CI 0.81, 1.70) after adjustment for established and novel cardiovascular risk factors. There was weak evidence that OR differed according to pre-existing CVD; the OR for MI in 187 participants with pre-existing CVD was 2.20 (1.04, 4.64) and 1.24 (0.84, 1.82) in 715 participants without (LR test for interaction p = 0.06). Geometric mean MMP-9 levels were higher in stroke cases than controls; 522 ng/mL (IQR 363, 673) vs 487 (IQR 393, 704), p = 0.045; however adjustments similarly attenuated the associations. Conclusions While serum MMP-9 is univariately associated with risk of MI and stroke, it is not a strong independent risk marker for either.

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

Diabet. Med. 28, 23–30 (2011)

Influence of area and individual lifecourse deprivation on health behaviours: findings from the British Women's Heart and Health Study.

Background Variable findings have been reported on the contribution of census-based measures of area deprivation over and above that of individual socioeconomic position (SEP) on health outcomes. This study aims to examine the association between residence in a deprived area and health behaviours (diet, smoking and physical inactivity), and how this association is influenced by lifecourse SEP of individuals. Design A population-based longitudinal study of women aged 60-79 years in 1999-2001 recruited from one general practice in each of 23 British towns. Methods Three thousand five hundred twenty-two women were included in the analyses. Area deprivation scores were derived from postcode for residence and lifecourse SEP scores were calculated using 10 individual level indicators of childhood and adult circumstances. To allow direct comparisons of effect of area deprivation and individual SEP, we standardized both measures by generating relative indices of inequality. Results Both area deprivation and lifecourse SEP were independent predictors of eating fruit and vegetables [odds ratio (OR): 2.87, 95% confidence interval (CI): 2.22-3.72; comparing highest with lowest area Index of Multiple Deprivation of inequality (OR: 3.07, 95% CI: 2.33-4.06) for lifecourse SEP index of inequality] and exercise habits (OR: 2.39, 95% CI: 1.86-3.06 area deprivation; OR: 2.7, 95% CI: 2.07-3.51 individual SEP). Area deprivation was a stronger predictor of smoking behaviour (OR: 2.34, 95% CI: 1.91-3.08) than individual lifecourse SEP (OR: 1.51, 95% CI: 1.17-1.95). Conclusion Most health behaviours among older women were independently associated with both living in deprived areas and individual lifecourse SEP. This suggests that additional health promotion approaches focusing on improving environments would have potential to improve health behaviour. Eur J Cardiovasc Prev Rehabil 16:169-173

Life-course socio-economic position, area deprivation and Type 2 diabetes: findings from the British Women's Heart and Health Study

Objectivesu2003 We examined whether area deprivation influenced risk of Type 2 diabetes, fasting blood glucose and insulin resistance over and above the effect of individual socio‐economic position (SEP) measured across the life course.

Circulating TNFα levels in older men and women do not show independent prospective relations with MI or stroke

Background Tumour necrosis factor alpha (TNFα) is a pro-inflammatory cytokine implicated in atherosclerotic plaque formation. We investigated whether circulating TNFα is prospectively associated with myocardial infarction (MI) or stroke in the older general population, independently of established cardiovascular risk factors and other inflammatory markers related to CHD risk. Methods We measured baseline TNFα concentrations in stored serum samples of 362 incident MI and 299 incident stroke cases and controls (2 per case, frequency matched by age, gender and town) who were ‘nested’ in parallel prospective studies of 4252 men and 4286 women aged 60–79 years assessed in general practices in 24 British towns in 1998–2000 and followed up for an average 7 years for fatal and non-fatal MI and stroke. Results TNFα levels were 11.4% (95% CI 9.5, 13.3%) higher among MI cases than controls; geometric mean 1.84 pg/mL compared to 1.63 pg/mL, p (difference) < 0.001. Participants in the top third of baseline TNFα levels had an age-adjusted odds ratio (OR) for MI of 1.75 (95%CI 1.22, 2.49) compared with those in the bottom third, which was reduced to 1.47 (95%CI 1.01, 2.14) after adjustment for established cardiovascular risk factors. However, further adjustment for C-reactive protein and interleukin-6 abolished the association OR 1.33 (95% CI 0.91, 1.66) and the linear trend. Excluding subjects with pre-existing CVD did not materially affect results. No significant association between TNFα and stroke was observed. Conclusions This study suggests that TNFα is not a strong independent risk marker for MI, and is not associated with risk of stroke.

The association between graded physical activity in postmenopausal British women, and the prevalence and incidence of hip and wrist fractures

BACKGROUNDnphysical activity is promoted for older women as a means of maintaining health and avoiding falls and fractures. Findings relating physical activity of older women to risk of falls and fracture are contradictory. The association between level of physical activity and prevalent and incident hip and wrist fractures was examined in a large representative sample of postmenopausal British women.nnnMETHODSndata from the British Womens Heart and Health Study, a cohort study of 4286 postmenopausal women aged 60-79, from 23 UK towns were used. Information on physical activity, anthropometry, falls and hip and wrist fractures from baseline examination and questionnaire (1999-2001) and follow-up questionnaire (2007) were available. Cross-sectional baseline prevalence data were analysed using logistic regression and cohort incidence data using a Cox proportional hazards model examining the association of physical activity with fracture outcomes.nnnRESULTSn3003 (70%) women, with complete baseline data, were studied. 13.6% had previously fractured a wrist and 1.3% a hip. Analyses unadjusted for confounders showed moderate protective associations between activity and fracture risk. After adjustment for confounders there was a weak trend towards fewer hip fractures (adjusted OR 0.13 [0.01, 1.18]) and more wrist fractures (adjusted OR 1.35 [0.76, 2.48]), amongst most active compared with inactive women. The crude incidence rate of wrist and/or hip fracture was 7.0 [5.9, 8.2] per 1000 person-years. No evidence was found for an association between physical activity and combined incident hip and/or wrist fracture (adjusted rate ratio inactive versus most active 1.69 [0.67, 4.24]).nnnCONCLUSIONnno clear associations between graded physical activity and hip/wrist fractures were seen but estimates were imprecise. Physical activities are heterogeneous and individual fracture types and mechanisms differ. Very large prospective observational studies are required to disentangle the precise effects of different activity patterns on different fracture types.

The association of renal impairment with all-cause and cardiovascular disease mortality

Background. The prognostic value of reduced glomerular filtration rate (GFR) was examined in a community-based cohort of British women. Methods. Serum creatinine measurements were available for 90% (n = 3851) of a representative random sample of 4286 women aged 60-79 years. GFR was estimated using the Modification of Diet in Renal Disease equation. Hazard ratios (HR) were calculated using Cox regression with outcomes of all-cause and cardiovascular disease (CVD) mortality. Results. Eight hundred and thirty-two women (21.6%) had a GFR <60 ml/min/1.73 m(2). Over a median follow-up of 5.6 years, there were 318 deaths (100 CVD deaths). Women with GFR <60 ml/min/1.73 m(2) compared to all others showed only a borderline increased risk of all-cause mortality [HR 1.35 (95% confidence intervals: 0.99, 1.85)] and CVD mortality [1.34 (0.97, 1.85)]. Adjustment for conventional CVD risk factors had little impact. The association with CVD mortality was attenuated in women with pre-existing CVD [adjusted HR: 0.51 (0.24, 1.04)]. Only the subset of women without CVD at baseline were at risk for later CVD death [adjusted HR: 1.80 (1.13, 2.88)]. Conclusions. A substantial proportion of older British women have GFR <60 ml/min/1.73 m(2) without strong evidence for statistical association with all-cause mortality. The effect on CVD mortality is partly explained by existing CVD and its risk factors. GFR measurement appears only to play a useful role in the subset of older women without pre-existing CVD who are at higher risk of premature CVD death.