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ABSTRACT: OBJECTIVE: We have examined the association between serum phosphate and alkaline phosphatase (ALP) with incident cardiovascular disease (CVD) outcomes and total mortality in older men.Approach and Results-A prospective study of 3381 men, aged 60 to 79 years, without a history of myocardial infarction or stroke followed up for an average 11 years during which there were 605 major CVD events (fatal coronary heart disease and nonfatal myocardial infarction, stroke, and CVD death) and 984 total deaths. ALP but not serum phosphate was associated with increased risk of coronary heart disease and overall CVD events which persisted after adjustment for CVD risk factors and markers of inflammation and after exclusion of men with chronic kidney disease (adjusted hazard ratio per SD, 1.19 [1.05, 1.34]; P=0.007 and 1.10 [1.01, 1.21]; P=0.04). In contrast, serum phosphate was only associated with increased CVD mortality owing to noncoronary heart disease or stroke causes (adjusted hazard ratio per SD, 1.35 [1.01, 1.83]; P=0.04). Both raised phosphate and ALP were associated with significantly increased total mortality after full adjustment and exclusion of men with chronic kidney disease. CONCLUSIONS: ALP but not serum phosphate is associated with coronary heart disease risk in elderly men. High levels of ALP and serum phosphate are both associated with increased total mortality.
Arteriosclerosis Thrombosis and Vascular Biology 02/2013; · 6.37 Impact Factor
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ABSTRACT: BACKGROUND AND PURPOSE: The association between adiposity and adipocytes and risk of stroke in older adults is uncertain. We have examined the association between adiposity measures and adipocytes (adiponectin and leptin) with incident stroke events in older men. METHODS: Prospective study of 3411 men aged 60 to 79 years with no previous diagnosis of myocardial infarction, heart failure, or stroke followed-up for an average of 9 years, during which there were 192 incident major stroke events. RESULTS: In age-adjusted analyses, body mass index and waist circumference were not significantly associated with risk of stroke in older men, although obese men (body mass index >30 kg/m(2)) showed the lowest risk of stroke. Despite the strong positive correlation between leptin and body mass index and waist circumference, risk of stroke was significantly increased in those in the top quartile of the leptin distribution. The increased risk remained after adjustment for potential confounders, including systolic blood pressure (adjusted hazard ratios top quartile versus bottom quartile: 2.03; confidence interval, 1.27-3.27]). Further adjustment for markers of inflammation (c-reactive protein), endothelial dysfunction (von Willebrand factor), fibrinolytic activity (d-dimer), and γ-glutamyl transferase attenuated the increased risk, but risk remained significantly increased (adjusted hazard ratios, 1.73; confidence interval, 1.06-2.83]). By contrast, no association was seen between adiponectin and risk of stroke. CONCLUSIONS: Conventional adiposity measures were not associated with increased stroke risk in older men. However, leptin (a good marker of percent fat mass), but not adiponectin, predicted stroke, suggesting a link between fat mass and stroke risk.
Stroke 11/2012; · 5.73 Impact Factor
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ABSTRACT: To determine how much physical activity (PA) is needed to protect against diabetes onset in older adults, whether protection is greater among overweight individuals, and whether taking up moderate activity in later life is beneficial.
Men (4,252) from a U.K. population-based cohort self-reported usual PA (regular walking and cycling, recreational activity, and sport) in 1996 and in 1998-2000, alongside other health behaviors and medical history. Fasting blood lipids were measured. Median follow-up was 7.1 years, during which 135 cases of type 2 diabetes (validated self-report) occurred.
Among 3,012 men free from cardiovascular disease and diabetes in 1998-2000, 9% reported no usual leisure-time PA, 23% occasional PA, and 15% vigorous PA. Compared with men reporting no activity, men reporting occasional, light, moderate, moderately vigorous, and vigorous PA had lower diabetes risks: hazard ratio (HR) 0.58 (95% CI 0.33-1.02), 0.39 (0.20-0.74), 0.38 (0.19-0.73), 0.39 (0.20-0.77), and 0.33 (0.16-0.70), respectively; P (trend) = 0.002, adjusted for age, social class, tobacco, alcohol, diet, and blood lipids. Adjustment for BMI, waist circumference, or fasting insulin attenuated HRs. HRs were stronger in men with BMI ≥28 vs. <28 kg/m(2) (interaction P = 0.02). Compared with men reporting light activity or less in 1996 and 2000, men who became at least moderately active by 2000 or remained at least moderately active at both times had adjusted HRs of 0.62 (0.34-1.12) and 0.51 (0.31-0.82), respectively.
Even light PA markedly reduced diabetes risk in older men, especially among the overweight or obese. Taking up or maintaining at least moderate PA in older adulthood strongly protected against diabetes.
Diabetes care 06/2012; 35(9):1876-83. · 8.09 Impact Factor
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ABSTRACT: Abnormalities in blood coagulation and the fibrinolytic system have been associated with increased risk of stroke, but few prospective studies have studied the associations in older adults. We have examined the associations between fibrin D-dimer, tissue-type plasminogen activator, and von Willebrand factor (vWF) and risk of stroke in older men and examined their predictive roles separately in normotensive and hypertensive men.
Prospective study of 3358 men aged 60 to 79 years with no previous diagnosis of myocardial infarction or stroke and without atrial fibrillation followed-up for an average of 9 years, during which there were 187 incident stroke events.
Increased levels of D-dimer and vWF were associated with significantly increased risk of major stroke events after adjustment for potential confounders, including systolic blood pressure (adjusted hazard ratios and 95% confidence interval per standard deviation increase in D-dimer and vWF were 1.24 [95% confidence interval, 1.08-1.44] and 1.25 [95% confidence interval, 1.09-1.45], respectively). No associations were seen with tPA after adjustment. The positive associations between D-dimer and vWF and incident stroke remained after additional adjustment for markers of inflammation (C-reactive protein, IL-6). D-dimer was associated with stroke in both normotensive and hypertensive men; vWF showed stronger associations in normotensive than in hypertensive men (test for interaction: P=0.52 for D-dimer; P<0.01 for vWF).
Fibrin D-dimer and vWF are associated with increased risk of stroke in older men. These associations were not explained by their associations with inflammation. D-dimer may be a useful marker to identify those at high risk for stroke among hypertensive men.
Stroke 03/2012; 43(5):1206-11. · 5.73 Impact Factor
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ABSTRACT: The relationship between γ-glutamyl transferase (GGT) and heart failure (HF) in older adults is unknown. We have examined the relationship between GGT, other markers of hepatic function (alanine aminotransferase, aspartate transaminase, and alkaline phosphatase), and incident HF in older men.
This was a prospective study of 3494 men aged 60 to 79 years with no diagnosed HF or myocardial infarction followed up for a mean period of 9 years, in whom there were 168 incident HF cases. Elevated GGT (top quartile, ≥38 U/L) was associated with significantly increased risk of incident HF in men aged<70 years but not in men aged≥70 years (test for age-GGT interaction, P<0.0001). The increased risk of HF associated with elevated GGT persisted after adjustment for a wide range of established and novel risk factors for HF, including diabetes, stroke, obesity, systolic blood pressure, atrial fibrillation, lung function, inflammation (C-reactive protein), endothelial dysfunction (von Willebrand factor), leptin, and N terminal pro brain natriuretic peptide (adjusted hazard ratio [95% CI], 1.91 [1.07, 3.42]). Other liver function markers showed no significant associations with HF after similar adjustments.
Elevated GGT was associated with increased risk of HF in men aged<70 years. Additional studies are now needed to determine the mechanisms responsible.
Arteriosclerosis Thrombosis and Vascular Biology 03/2012; 32(3):830-5. · 6.37 Impact Factor
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ABSTRACT: We examined the relationship between body mass index (BMI), waist circumference, and incident HF in men with and without pre-existing coronary heart disease (CHD) and assessed the contribution of plasma leptin concentration to these associations.
Leptin has been proposed as a potential link between obesity and heart failure (HF).
This was a prospective study of 4,080 men age 60 to 79 years with no diagnosed HF followed for a mean period of 9 years, in whom there were 228 incident HF cases.
Increased BMI was associated with significantly increased risk of HF in men with and without pre-existing CHD (myocardial infarction or angina) after adjustment for cardiovascular risk factors including C-reactive protein. The adjusted hazard ratios (HRs) associated with a 1-SD increase in BMI were 1.37 (95% confidence interval [CI]: 1.09 to 1.72) and 1.18 (95% CI: 1.00 to 1.39) in men with and without CHD, respectively. Increased leptin was significantly associated with an increased risk of HF in men without pre-existing CHD, independent of BMI and potential mediators (adjusted HR for a 1-SD increase in log leptin: 1.30 [95% CI: 1.06 to 1.61]; p = 0.01). However, no association was seen in those with pre-existing CHD (corresponding HR: 1.06 [95% CI: 0.77 to 1.45]; p = 0.72). Adjustment for leptin abolished the association between BMI and HF in men with no CHD; in those with CHD, the association between BMI and HF remained significant (p = 0.03). Similar patterns were seen for waist circumference.
In the absence of established CHD, the association between obesity and HF may be mediated by plasma leptin. In those with CHD, obesity appears to increase the risk of HF independent of leptin.
Journal of the American College of Cardiology 10/2011; 58(18):1870-7. · 14.16 Impact Factor
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ABSTRACT: We aimed to compare the predictive capabilities of N-terminal pro-brain natriuretic peptide (NT-proBNP) and C-reactive protein (CRP) for risk of cardiovascular disease (CVD) in older men with and without pre-existing CVD.
The clinical utility of NT-proBNP in CVD risk stratification in the general population remains unclear.
A prospective study of 3,649 men age 60 to 79 years were followed for a mean of 9 years during which there were 608 major CVD events (major fatal and nonfatal coronary heart disease, stroke, and CVD death).
NT-proBNP was significantly associated with risk of all major CVD outcomes after adjustment for CV risk factors in both men with and without CVD. The adjusted standardized hazard ratios for CVD events in those without pre-existing CVD and those with pre-existing CVD were 1.49 (95% confidence interval [CI]: 1.33 to 1.65) and 1.52 (95% CI: 1.33 to 1.75), respectively. CRP was associated with CVD outcomes only in men without pre-existing CVD (adjusted standardized hazard ratios: 1.22 [95% CI: 1.10 to 1.34] and 1.00 [95% CI: 0.86 to 1.38], respectively). NT-proBNP was more strongly associated with CVD outcome than CRP, particularly among those with pre-existing CVD. Inclusion of NT-proBNP in a Framingham-based model yielded significant improvement in C-statistics in both men with and without CVD and resulted in a net reclassification improvement of 8.8% (p = 0.0009) and 8.2% (p < 0.05), respectively, for major CVD events. Inclusion of CRP in the Framingham-based model did not improve prediction in either group (net reclassification improvement 3.8% and 0.6%, respectively).
NT-proBNP, but not CRP, improved prediction of major CVD events in older men with and without pre-existing CVD.
Journal of the American College of Cardiology 06/2011; 58(1):56-64. · 14.16 Impact Factor
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ABSTRACT: We have examined the influence of age at onset and duration on the impact of diabetes mellitus on cardiovascular disease risk and all cause-mortality among men aged 60 to 79 years.
A prospective study of 4045 men aged 60 to 79 years followed up for a mean of 9 years, during which there were 372 major coronary heart disease (CHD) events (fatal and nonfatal myocardial infarction [MI]), 455 deaths from cardiovascular disease, and 1112 deaths from all causes. Men were classified as having (1) no history of MI and diabetes, (2) late-onset diabetes (diagnosed at ≥60 years or undiagnosed diabetes [fasting blood glucose level, >126.1 mg/dL]), (3) early-onset diabetes (diagnosed before age 60 years), or (4) prior MI.
Men who had both MI and diabetes were excluded. Both early and late onset of diabetes were associated with a significantly increased risk of major CHD events and all-cause mortality compared with nondiabetic men who had no CHD, even after adjustment for conventional risk factors and novel risk markers (levels of C-reactive protein and von Willebrand factor and renal dysfunction). Only men with early-onset diabetes (associated with a duration of 16.7 years) showed risk similar to those with previous MI and no diabetes. The adjusted relative risks (95% confidence intervals) for major CHD events were 1.00 (reference), 1.54 (1.07-2.21), 2.39 (1.41-4.05), and 2.51 (1.88-3.36) for groups 1 through 4, respectively.
Both early and late onset of diabetes are associated with increased risk of major CHD events and mortality, but only early onset of diabetes (associated with >10 years' duration) appears to be a CHD equivalent.
Archives of internal medicine 03/2011; 171(5):404-10. · 11.46 Impact Factor
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Barbara J Jefferis,
Peter Whincup,
Paul Welsh,
Goya Wannamethee,
Ann Rumley, Lucy Lennon,
Andy Thomson,
Debbie Lawlor,
Claire Carson,
Shah Ebrahim,
Gordon Lowe
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ABSTRACT: 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.
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.
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; 522ng/mL (IQR 363, 673) vs 487 (IQR 393, 704), p=0.045; however adjustments similarly attenuated the associations.
While serum MMP-9 is univariately associated with risk of MI and stroke, it is not a strong independent risk marker for either.
Atherosclerosis 08/2009; 208(2):557-63. · 3.79 Impact Factor
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ABSTRACT: To examine whether adult social class and childhood social class are related to metabolic syndrome in later life, independent of adult behavioral factors.
This was a population-based cross-sectional study comprising 2,968 men aged 60-79 years.
Adult social class and childhood social class were both inversely related to metabolic syndrome. Mutual adjustment attenuated the relation of metabolic syndrome with childhood social class; that with adult social class was little affected. However, the relation with adult social class was markedly attenuated by adjustment for smoking status, physical activity, and alcohol consumption. High waist circumference was independently associated with adult social class.
The association between adult social class and metabolic syndrome was largely explained by behavioral factors. In addition, central adiposity, a component of metabolic syndrome, was associated with adult social class. Focusing on healthier behaviors and obesity, rather than specific efforts to reduce social inequalities surrounding metabolic syndrome, is likely to be particularly important in reducing social inequalities that affect people with coronary disease.
Diabetes care 10/2008; 31(12):2380-2. · 8.09 Impact Factor
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Naveed Sattar,
Alex McConnachie,
A Gerald Shaper,
Gerard J Blauw,
Brendan M Buckley,
Anton J de Craen,
Ian Ford,
Nita G Forouhi,
Dilys J Freeman,
J Wouter Jukema, Lucy Lennon,
Peter W Macfarlane,
Michael B Murphy,
Chris J Packard,
David J Stott,
Rudi G Westendorp,
Peter H Whincup,
James Shepherd,
S Goya Wannamethee
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ABSTRACT: Clinical use of criteria for metabolic syndrome to simultaneously predict risk of cardiovascular disease and diabetes remains uncertain. We investigated to what extent metabolic syndrome and its individual components were related to risk for these two diseases in elderly populations.
We related metabolic syndrome (defined on the basis of criteria from the Third Report of the National Cholesterol Education Program) and its five individual components to the risk of events of incident cardiovascular disease and type 2 diabetes in 4812 non-diabetic individuals aged 70-82 years from the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER). We corroborated these data in a second prospective study (the British Regional Heart Study [BRHS]) of 2737 non-diabetic men aged 60-79 years.
In PROSPER, 772 cases of incident cardiovascular disease and 287 of diabetes occurred over 3.2 years. Metabolic syndrome was not associated with increased risk of cardiovascular disease in those without baseline disease (hazard ratio 1.07 [95% CI 0.86-1.32]) but was associated with increased risk of diabetes (4.41 [3.33-5.84]) as was each of its components, particularly fasting glucose (18.4 [13.9-24.5]). Results were similar in participants with existing cardiovascular disease. In BRHS, 440 cases of incident cardiovascular disease and 105 of diabetes occurred over 7 years. Metabolic syndrome was modestly associated with incident cardiovascular disease (relative risk 1.27 [1.04-1.56]) despite strong association with diabetes (7.47 [4.90-11.46]). In both studies, body-mass index or waist circumference, triglyceride, and glucose cutoff points were not associated with risk of cardiovascular disease, but all five components were associated with risk of new-onset diabetes.
Metabolic syndrome and its components are associated with type 2 diabetes but have weak or no association with vascular risk in elderly populations, suggesting that attempts to define criteria that simultaneously predict risk for both cardiovascular disease and diabetes are unhelpful. Clinical focus should remain on establishing optimum risk algorithms for each disease.
The Lancet 07/2008; 371(9628):1927-35. · 38.28 Impact Factor
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ABSTRACT: The objective of this study was to assess the relationship between putative markers of endothelial dysfunction (tissue plasminogen activator [t-PA] antigen and von Willebrand factor [vWF] antigen) and development of type 2 diabetes, as well as the role of inflammation, adipokines, hepatic function, and insulin resistance in modifying these relationships.
This was a prospective study of 3,562 nondiabetic men aged 60-79 years followed up for an average of 7 years during which there were 162 incident cases of type 2 diabetes.
Elevated t-PA (top third) was associated with a near threefold increase in risk of diabetes compared with the risk in those in the bottom third after adjustment for lifestyle factors and waist circumference (relative risk [RR] 2.98 [95%CI 1.79-5.00]; P(trend) < 0.0001); weaker but significant (marginal) associations were seen with vWF (1.24 [0.83-1.85]; P = 0.05 for trend). Both biomarkers of endothelial dysfunction correlated significantly with markers of inflammation (interleukin-6 [IL-6] and C-reactive protein [CRP]), hepatic function (gamma-glutamyl transferase [GGT]), and insulin resistance, with t-PA showing stronger associations with adiposity, hepatic function, and insulin resistance than vWF. t-PA was also significantly and inversely associated with adiponectin. Adjustment for IL-6, adiponectin, and GGT attenuated the association of incident diabetes with vWF (1.06 [0.71-1.60]), but the relationship seen with t-PA remained significant (adjusted RR 2.19 [1.29-3.70]). Subsequent adjustment for insulin attenuated the association further, but t-PA was still associated with a significant increase in risk (1.66 [0.96-2.85]; P(trend) = 0.02).
t-PA antigen, but not vWF antigen, is independently associated with risk of type 2 diabetes.
Diabetes care 06/2008; 31(5):995-1000. · 8.09 Impact Factor
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ABSTRACT: To examine the prospective relation of social engagement with cardiovascular disease (CVD) mortality, taking into account behavioral factors (smoking, physical activity, body weight, and alcohol consumption), socioeconomic factors, and presence of comorbidity and disability.
A socioeconomically representative cohort of 5925 men aged 52-74 years from 24 British towns was followed up from 1992-2006. A scale from 0-9 was used based on questions reflecting the frequency and extent of social engagement in 1992.
CVD mortality risk decreased with increasing social engagement score-age-adjusted hazard ratio (HR) for those with the highest social engagement score of 8-9 was 0.42 (95% confidence interval [95%CI], 0.32-0.53) compared to those with the lowest scores of 0-3 (p for trend < or = 0.0001). Further adjustment for behavioral factors (smoking, alcohol, physical activity, and body weight), disability, comorbidity, and socioeconomic factors reduced the strength of this association, although strong evidence of an association remained: HR 0.70 (95%CI, 0.53-0.93) for highest versus lowest social engagement scores (p for trend = 0.0004). Although the association appeared somewhat stronger in subjects with preexisting CVD (HR 0.59 for highest vs. lowest social engagement scores) than in those without (HR 0.79), there was no evidence of an interaction between social engagement and preexisting CVD (p = 0.61).
In our study of older men, social engagement appeared to have a modest protective effect on CVD mortality independent of behavioral factors, socioeconomic conditions, disease, and disability.
Annals of epidemiology 06/2008; 18(6):476-83. · 2.95 Impact Factor
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John Danesh,
Stephen Kaptoge,
Andrea G Mann,
Nadeem Sarwar,
Angela Wood,
Sara B Angleman,
Frances Wensley,
Julian P T Higgins, Lucy Lennon,
Gudny Eiriksdottir,
Ann Rumley,
Peter H Whincup,
Gordon D O Lowe,
Vilmundur Gudnason
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ABSTRACT: The relevance to coronary heart disease (CHD) of cytokines that govern inflammatory cascades, such as interleukin-6 (IL-6), may be underestimated because such mediators are short acting and prone to fluctuations. We evaluated associations of long-term circulating IL-6 levels with CHD risk (defined as nonfatal myocardial infarction [MI] or fatal CHD) in two population-based cohorts, involving serial measurements to enable correction for within-person variability. We updated a systematic review to put the new findings in context.
Measurements were made in samples obtained at baseline from 2,138 patients who had a first-ever nonfatal MI or died of CHD during follow-up, and from 4,267 controls in two cohorts comprising 24,230 participants. Correction for within-person variability was made using data from repeat measurements taken several years apart in several hundred participants. The year-to-year variability of IL-6 values within individuals was relatively high (regression dilution ratios of 0.41, 95% confidence interval [CI] 0.28-0.53, over 4 y, and 0.35, 95% CI 0.23-0.48, over 12 y). Ignoring this variability, we found an odds ratio for CHD, adjusted for several established risk factors, of 1.46 (95% CI 1.29-1.65) per 2 standard deviation (SD) increase of baseline IL-6 values, similar to that for baseline C-reactive protein. After correction for within-person variability, the odds ratio for CHD was 2.14 (95% CI 1.45-3.15) with long-term average ("usual") IL-6, similar to those for some established risk factors. Increasing IL-6 levels were associated with progressively increasing CHD risk. An updated systematic review of electronic databases and other sources identified 15 relevant previous population-based prospective studies of IL-6 and clinical coronary outcomes (i.e., MI or coronary death). Including the two current studies, the 17 available prospective studies gave a combined odds ratio of 1.61 (95% CI 1.42-1.83) per 2 SD increase in baseline IL-6 (corresponding to an odds ratio of 3.34 [95% CI 2.45-4.56] per 2 SD increase in usual [long-term average] IL-6 levels).
Long-term IL-6 levels are associated with CHD risk about as strongly as are some major established risk factors, but causality remains uncertain. These findings highlight the potential relevance of IL-6-mediated pathways to CHD.
PLoS Medicine 05/2008; 5(4):e78. · 16.27 Impact Factor
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ABSTRACT: Aging is associated with significant changes in body composition. Body mass index (BMI; in kg/m(2)) is not an accurate indicator of overweight and obesity in the elderly.
We examined the relation between other anthropometric indexes of body composition (both muscle mass and body fat) and all-cause mortality in men aged 60-79 y.
The study was a prospective study of 4107 men aged 60-79 y with no diagnosis of heart failure and who were followed for a mean period of 6 y, during which time there were 713 deaths.
Underweight men (BMI < 18.5) had exceptionally high mortality rates. After the exclusion of these men, increased adiposity [BMI, waist circumference (WC), and waist-to-hip ratio] showed little relation with mortality after adjustment for lifestyle characteristics. Muscle mass [indicated by midarm muscle circumference (MAMC)] was significantly and inversely associated with mortality. After adjustment for MAMC, obesity markers, particularly high WC (>102 cm) and waist-to-hip ratio (top quartile), were associated with increased mortality. A composite measure of MAMC and WC most effectively predicted mortality. Men with low WC (</=102 cm) and above-median muscle mass showed the lowest mortality risk. Men with WC > 102 cm and above-median muscle mass showed significantly increased mortality [age-adjusted relative risk: 1.36; 95% CI: 1.07, 1.74), and this increased to 1.55 (95% CI: 1.01, 2.39) in those with WC > 102 and low MAMC.
The findings suggest that the combined use of both WC and MAMC provides simple measures of body composition to assess mortality risk in older men.
American Journal of Clinical Nutrition 11/2007; 86(5):1339-46. · 6.67 Impact Factor
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ABSTRACT: We examined patterns in medication use for secondary prevention of cerebrovascular disease in older British men from 1999 to 2005, and investigated socio-demographic and disease-related influences on medication use.
Percentage use of antiplatelet drugs, blood pressure-lowering drugs and statins use was calculated in men, aged 65-87 years in 2005, who had been diagnosed with stroke or transient ischaemic attack (TIA) from a population-based cohort based in one general practice in each of 24 British towns.
In 1999, most men with cerebrovascular disease received antiplatelet drugs (67%). However, a few received blood pressure-lowering drugs (50%) and statins (13%). By 2005, the use of all drug types had increased; at least half of the patients received each type of drug. However, only one-third of patients received all three medication types and combined blood pressure treatment was limited. Older age, a diagnosis of TIA rather than stroke and absence of co-existing coronary heart disease were associated with lower rates of use of specific medication categories.
Despite improvements in secondary prevention medication use, there is scope for achieving the full potential of these medications, particularly by increasing combination blood pressure treatment and statin use and ensuring that older patients receive the benefits of prevention.
Journal of Public Health 10/2007; 29(3):251-7. · 2.06 Impact Factor
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ABSTRACT: High adiponectin levels have been associated with reduced cardiovascular risk but have been shown to predict mortality in those at high risk for vascular disease. We examined the relationship between adiponectin levels and mortality in older men with and without diagnosed cardiovascular disease (CVD) and heart failure.
Prospective study of 4046 men aged 60 to 79 years drawn from general practices in 24 British towns and followed up for a mean of 6 years, during which 734 deaths occurred. The men were divided into the following groups according to the presence of physician-diagnosed CVD and heart failure: (1) those with no CVD or heart failure; (2) those with CVD but without heart failure; and (3) those with heart failure (with or without CVD).
After adjustment for a wide range of baseline characteristics, adiponectin levels were positively associated with significantly increased all-cause and CVD mortality in men with no diagnosed CVD or heart failure (top third vs bottom third adjusted relative risk, 1.55 [95% confidence interval (CI), 1.19-2.02; P = .002 for trend] vs 1.53 [95% CI, 1.03-2.27; P = .02 for trend]), as well as in men with diagnosed heart failure ([adjusted relative risk, 2.37 [95% CI, 0.64-8.79; P = .04 for trend] vs 3.43 [95% CI, 0.54-21.70; P = .008 for trend]). No association was seen in those with diagnosed CVD without heart failure. Adjustment for weight loss and renal function made minor differences to these relationships.
In older men, high adiponectin levels are associated with increased all-cause and CVD mortality in those with heart failure and those free of CVD. Such observations suggest that adiponectin levels may reflect a balance of both protective and harmful factors.
Archives of Internal Medicine 08/2007; 167(14):1510-7. · 11.46 Impact Factor
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ABSTRACT: To assess the extent to which inflammatory, procoagulant, and endothelial biomarkers modify the relationship between diminished renal function and cardiovascular mortality.
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).
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.
European Heart Journal 12/2006; 27(24):2975-81. · 10.48 Impact Factor
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ABSTRACT: Although there has been concern about the levels of carbon monoxide exposure, particularly among older people, little is known about COHb levels and their determinants in the general population. We examined these issues in a study of older British men.
Cross-sectional study of 4252 men aged 60-79 years selected from one socially representative general practice in each of 24 British towns and who attended for examination between 1998 and 2000. Blood samples were measured for COHb and information on social, household and individual factors assessed by questionnaire. Analyses were based on 3603 men measured in or close to (< 10 miles) their place of residence.
The COHb distribution was positively skewed. Geometric mean COHb level was 0.46% and the median 0.50%; 9.2% of men had a COHb level of 2.5% or more and 0.1% of subjects had a level of 7.5% or more. Factors which were independently related to mean COHb level included season (highest in autumn and winter), region (highest in Northern England), gas cooking (slight increase) and central heating (slight decrease) and active smoking, the strongest determinant. Mean COHb levels were more than ten times greater in men smoking more than 20 cigarettes a day (3.29%) compared with non-smokers (0.32%); almost all subjects with COHb levels of 2.5% and above were smokers (93%). Pipe and cigar smoking was associated with more modest increases in COHb level. Passive cigarette smoking exposure had no independent association with COHb after adjustment for other factors. Active smoking accounted for 41% of variance in COHb level and all factors together for 47%.
An appreciable proportion of men have COHb levels of 2.5% or more at which symptomatic effects may occur, though very high levels are uncommon. The results confirm that smoking (particularly cigarette smoking) is the dominant influence on COHb levels.
BMC Public Health 01/2006; 6:189. · 2.00 Impact Factor
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ABSTRACT: We have examined the relationship between hepatic enzymes, the metabolic syndrome, insulin resistance, and type 2 diabetes and assessed the potential of hepatic enzyme measurements in determining diabetes risk.
We conducted a prospective study of 3,500 nondiabetic men aged 60-79 years who were followed-up for a mean period of 5 years and in whom there were 100 incident type 2 diabetes cases.
In cross-sectional analyses, alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) were strongly associated with obesity, insulin resistance, and the metabolic syndrome. Prospectively, the risk of type 2 diabetes significantly increased with increasing levels of ALT and GGT even after adjustment for confounders including BMI (top versus bottom quarter ALT: relative risk 2.72 [95% CI 1.47-5.02]; GGT: 3.68 [1.68-8.04]). Additional adjustment for insulin resistance attenuated the effects, but the relationships with ALT and GGT remained significant (1.91 [1.01-3.60] and 2.69 [1.21-5.97], respectively). Further adjustment for inflammatory markers (C-reactive protein) made minor differences. Among high-risk subjects (obese men or those with the metabolic syndrome), elevated GGT and ALT enhanced the prediction of diabetes risk.
Elevated levels of ALT and GGT within the normal range are independent predictors of type 2 diabetes in older men and are useful additional measures in identifying those at high risk of diabetes.
Diabetes Care 01/2006; 28(12):2913-8. · 8.09 Impact Factor
