Showing papers by "Peter W.F. Wilson published in 2010"
TL;DR: Current estrogen use may help to maintain bone in women, whereas current smoking was associated with bone loss in men, this population‐based study suggests.
Abstract: Few studies have evaluated risk factors for bone loss in elderly women and men. Thus, we examined risk factors for 4-year longitudinal change in bone mineral density (BMD) at the hip, radius, and spine in elders. Eight hundred elderly women and men from the population-based Framingham Osteoporosis Study had BMD assessed in 1988-1989 and again in 1992-1993. BMD was measured at femoral neck, trochanter, Ward's area, radial shaft, ultradistal radius, and lumbar spine using Lunar densitometers. We examined the relation of the following factors at baseline to percent BMD loss: age, weight, change in weight, height, smoking, caffeine, alcohol use, physical activity, serum 25-OH vitamin D, calcium intake, and current estrogen replacement in women. Multivariate regression analyses were conducted with simultaneous adjustment for all variables. Mean age at baseline was 74 years ± 4.5 years (range, 67-90 years). Average 4-year BMD loss for women (range, 3.4-4.8%) was greater than the loss for men (range, 0.2-3.6%) at all sites; however, BMD fell with age in both elderly women and elderly men. For women, lower baseline weight, weight loss in interim, and greater alcohol use were associated with BMD loss. Women who gained weight during the interim gained BMD or had little change in BMD. For women, current estrogen users had less bone loss than nonusers; at the femoral neck, nonusers lost up to 2.7% more BMD. For men, lower baseline weight and weight loss also were associated with BMD loss. Men who smoked cigarettes at baseline lost more BMD at the trochanter site. Surprisingly, bone loss was not affected by caffeine, physical activity, serum 25-OH vitamin D, or calcium intake. Risk factors consistently associated with bone loss in elders include female sex, thinness, and weight loss, while weight gain appears to protect against bone loss for both men and women. This population-based study suggests that current estrogen use may help to maintain bone in women, whereas current smoking was associated with bone loss in men. Even in the elderly years, potentially modifiable risk factors, such as weight, estrogen use, and cigarette smoking are important components of bone health.
719 citations
TL;DR: Clinical descriptors can assist clinicians in identifying high-risk patients within the broad range of risk for outpatients with atherothrombosis using simple clinical descriptors.
Abstract: Context Clinicians and trialists have difficulty with identifying which patients are highest risk for cardiovascular events. Prior ischemic events, polyvascular disease, and diabetes mellitus have all been identified as predictors of ischemic events, but their comparative contributions to future risk remain unclear. Objective To categorize the risk of cardiovascular events in stable outpatients with various initial manifestations of atherothrombosis using simple clinical descriptors. Design, Setting, and Patients Outpatients with coronary artery disease, cerebrovascular disease, or peripheral arterial disease or with multiple risk factors for atherothrombosis were enrolled in the global Reduction of Atherothrombosis for Continued Health (REACH) Registry and were followed up for as long as 4 years. Patients from 3647 centers in 29 countries were enrolled between 2003 and 2004 and followed up until 2008. Final database lock was in April 2009. Main Outcome Measures Rates of cardiovascular death, myocardial infarction, and stroke. Results A total of 45 227 patients with baseline data were included in this 4-year analysis. During the follow-up period, a total of 5481 patients experienced at least 1 event, including 2315 with cardiovascular death, 1228 with myocardial infarction, 1898 with stroke, and 40 with both a myocardial infarction and stroke on the same day. Among patients with atherothrombosis, those with a prior history of ischemic events at baseline (n = 21 890) had the highest rate of subsequent ischemic events (18.3%; 95% confidence interval [CI], 17.4%-19.1%); patients with stable coronary, cerebrovascular, or peripheral artery disease (n = 15 264) had a lower risk (12.2%; 95% CI, 11.4%-12.9%); and patients without established atherothrombosis but with risk factors only (n = 8073) had the lowest risk (9.1%; 95% CI, 8.3%-9.9%) (P Conclusion Clinical descriptors can assist clinicians in identifying high-risk patients within the broad range of risk for outpatients with atherothrombosis.
612 citations
TL;DR: Metformin use may decrease mortality among patients with diabetes when used as a means of secondary prevention, including subsets of patients in whom met formin use is not now recommended.
Abstract: Results: The mortality rates were 6.3% (95% confidence interval[CI],5.2%-7.4%)withmetforminand9.8%8.4%11.2%)withoutmetformin;theadjustedhazardratio(HR) was0.76(0.65-0.89;P.001).Associationwithlowermortalitywasconsistentamongsubgroups,noticeablyinpatients withahistoryofcongestiveheartfailure(HR,0.69;95%CI, 0.54-0.90;P=.006),patientsolderthan65years(0.77;0.620.95;P=.02),andpatientswithanestimatedcreatinineclearanceof30to60mL/min/1.73m 2 (0.64;95%CI,0.48-0.86; P=.003)(toconvertcreatinineclearancetomL/s/m 2 ,multiply by 0.0167). Conclusions: Metformin use may decrease mortality among patients with diabetes when used as a means of secondary prevention, including subsets of patients in whom metformin use is not now recommended. Metformin use should be tested prospectively in this population to confirm its effect on survival. Arch Intern Med. 2010;170(21):1892-1899
342 citations
TL;DR: The purpose of this Advisory is to highlight the gaps in existing research on cardiovascular disease (CVD) among Asian Americans, and to serve as a call to action on behalf of the American Heart Association to address these areas of need.
Abstract: In 2009, President Obama signed an Executive Order calling for strategies to improve the health of Asian Americans and to seek data on the health disparities in Asian American subgroups.1 Data on Asian American subgroups are scarce and many health disparities remain unknown. The purpose of this Advisory is to highlight the gaps in existing research on cardiovascular disease (CVD) among Asian Americans, and to serve as a call to action on behalf of the American Heart Association to address these areas of need.
Asian Americans are the fastest growing racial/ethnic group in the United States, representing 25% of all foreign-born people in the United States.2 They are projected to reach nearly 34 million by 2050.3 Several major Federal surveys (eg, the American Community Survey, the National Health Interview Survey, and the Behavioral Risk Factor Surveillance Survey) only recently started to classify Asian Americans into 7 subgroups: Asian Indian, Chinese, Filipino, Korean, Japanese, Vietnamese, and Other Asian. The first six of these subgroups together constitute >90% of Asian Americans in the United States.4 Although some data are available on Asian subgroups from these major federal surveys, in general, these data are not available for public use because of the privacy concerns resulting from the small sample sizes within subgroups. This situation limits their utility for health-related research.
Because health surveys and questionnaires almost universally combine persons of Asian ancestry into a single group, the heterogeneity within this classification is masked. Socioeconomic and cultural factors have been found to be associated with CVD and its risk factors, which is why it is important to understand these differences among Asian subgroups. The Table shows the number of persons in each group based on the most recent US Census data available (American Community Survey, 2008), with the recognition that …
214 citations
TL;DR: Although women with CHD had higher sdLDL-C concentrations than controls, this difference was not seen in men, and some of the high residual risk of future CHD events in CHD patients had mean LDL-C concentration above the goal of <2.6 mmol/L (<100 mg/dL).
Abstract: Objective: We sought to establish reference values for a new direct assay for small dense LDL cholesterol (sdLDL-C) and to measure sdLDL-C concentrations in patients with established coronary heart disease (CHD) vs controls.
Methods: Direct LDL-C and sdLDL-C were measured in samples from 3188 male and female participants of the Framingham Offspring Study, including 173 men and 74 women with CHD.
Results: Postmenopausal status and male sex were associated with higher sdLDL-C concentrations ( P < 0.0001). Cholesterol-lowering medication use was more frequent ( P < 0.0001) in CHD patients than in controls (46.8% vs 11.4% in men; 35.1% vs 8.8% in women). In men, mean LDL-C was lower in CHD than in controls (3.22 vs 3.51 mmol/L, P < 0.0001), whereas mean sdLDL-C concentrations were similar (0.83 vs 0.84 mmol/L, P = 0.609). In women, mean LDL-C was similar in CHD and controls (3.53 vs 3.46 mmol/L, P = 0.543), but mean sdLDL-C was higher (0.83 vs 0.68 mmol/L, P = 0.0015). The mean percentage of LDL-C as sdLDL-C was higher in both men and women with CHD than controls ( P < 0.01). Increased LDL-C and sdLDL-C were found in 10.4% and 22.0% of men and in 24.3% and 27.8% of women with CHD, respectively.
Conclusions: Despite 4-fold greater cholesterol-lowering therapy use, CHD patients had mean LDL-C concentrations above the LDL-C goal of <2.6 mmol/L (<100 mg/dL). Although women with CHD had higher sdLDL-C concentrations than controls, this difference was not seen in men. These findings may explain some of the high residual risk of future CHD events in CHD patients.
181 citations
TL;DR: Aspirin has been shown to be effective in reducing cardiovascular morbidity and mortality in high-risk patients with myocardial infarction (MI) or stroke (secondary prevention), and its net benefit among patients with no previous cardiovascular events is more controversial.
143 citations
TL;DR: Bleeding risk increased substantially with a score >10, and this score can assist clinicians in predicting the risk of serious bleeding and making decisions on antithrombotic therapy in outpatients.
Abstract: Aims To develop a risk score to quantify bleeding risk in outpatients with or at risk of atherothrombosis.
Methods and results We studied patients in the REACH Registry, a cohort of 68 236 patients with/at risk of atherothrombosis. The outcome of interest was serious bleeding (non-fatal haemorrhagic stroke or bleeding leading to hospitalization and transfusion) over 2 years. Risk factors for bleeding were assessed using modified regression analysis. Multiple potential scoring systems based on the least complex models were constructed. Competing scores were compared on their discriminative ability via logistic regression. The score was validated externally using the CHARISMA population. From a final cohort of 56 616 patients, 804 (1.42%, 95% confidence interval 1.32–1.52) experienced serious bleeding between baseline and 2 years. A nine-item bleeding risk score (0–23 points) was constructed (age, peripheral arterial disease, congestive heart failure, diabetes, hypertension, smoking, antiplatelets, oral anticoagulants, hypercholesterolaemia). Observed incidence of bleeding at 2 years was: 0.46% (score ≤6); 0.95% (7–8); 1.25% (9–10); 2.76% (≥11). The score's discriminative performance was consistent in CHARISMA and REACH (c-statistics 0.64 and 0.68, respectively); calibration in the CHARISMA population was very good (modified Hosmer-Lemeshow c 2 = 4.74; P = 0.69).
Conclusion Bleeding risk increased substantially with a score >10. This score can assist clinicians in predicting the risk of serious bleeding and making decisions on antithrombotic therapy in outpatients.
120 citations
TL;DR: The relatively recent evolution of multiple forms of a member of a new defensin related group of peptides that are termed ovodefensins, may be an adaptation to increase expression or the first steps in divergent evolution of the gene in chickens.
Abstract: Background
Egg white must provide nutrients and protection to the developing avian embryo. One way in which this is achieved is an arsenal of antimicrobial proteins and peptides which are essentially extensions of the innate immune system. Gallin is a recently identified member of a family of peptides that are found in egg white. The function of this peptide family has not been identified and they are potentially antimicrobial.
85 citations
TL;DR: The Health ABC HF model adequately predicted 5-year heart failure risk in a large community-based study, providing support for the external validity of the model.
Abstract: Background—The recently developed and internally validated Health ABC HF model uses 9 routinely available clinical variables to determine incident heart failure risk. In this study, we sought to externally validate the Health ABC HF model. Methods and Results—Observed 5-year incidence of heart failure, defined as first hospitalization for new-onset heart failure, was compared with 5-year risk estimates derived from the Health ABC HF model among participants without heart failure at baseline in the Cardiovascular Health Study. During follow-up, 400 of 5335 (7.5%) participants developed heart failure over 5 years versus 364 (6.8%) predicted by the Health ABC HF model (predicted-to-observed ratio, 0.90). Observed versus predicted 5-year heart failure probabilities were 3.2% versus 2.8%, 9.0% versus 7.0%, 15.9% versus 13.7%, and 24.6% versus 30.8% for the 20% 5-year risk categories, respectively. The Hosmer-Lemeshow χ2 was 14.72 (degrees of freedom, 10; P=0.14), and the C inde...
64 citations
TL;DR: Common modifiable risk factors accurately discriminate women and men at risk for HF diagnosed in either outpatient or inpatient settings and approximately two thirds of new HF cases in the insured population were diagnosed in outpatients.
Abstract: Background—Studies on the incidence and predictors of heart failure (HF) are often restricted to elderly persons or identify only inpatient cases. Methods and Results—We determined the incidence and predictors of new HF diagnosed in either outpatient or inpatient settings, among 359 947 women and men (age ≥18 years) insured by Kaiser Permanente Georgia at any time during calendar years 2000 to 2005. Subjects were free of HF at baseline, and incident HF was identified with ICD-9 codes (1 inpatient or 2 outpatient HF visits). We developed multivariable Cox models to assess the association of antecedent factors (coronary heart disease, hypertension, diabetes mellitus, atrial fibrillation, and valvular heart disease) with incident HF. Separate models were created for each sex and for newly diagnosed HF in outpatient or inpatient settings. There were 4001 incident HF cases (50% women and 48% in subjects <65 years old), during 1 015 794 person-years of follow-up. The incidence rate of HF was greater in men than...
62 citations
TL;DR: Diabetic patients in the REACH Registry have an increased risk of cardiovascular events compared to nondiabetic subjects related to the number of atherothrombotic sites, and these differences persisted after adjusting for gender and age.
Abstract: The objective of this study was to determine cardiovascular event rates in diabetic patients and nondiabetic subjects from the REACH Registry with established coronary artery disease, cerebrovascular disease, peripheral arterial disease, or multiple risk factors for atherothrombosis. REACH is an international, prospective, and contemporaneous cohort of patients with ≥3 atherothrombotic risk factors only or established atherothrombotic disease, of which 30,043 have diabetes. The main outcomes after 1-year follow-up were cardiovascular death, myocardial infarction, stroke, major adverse cardiovascular events (MACEs; cardiovascular death, myocardial infarction, or stroke), and MACEs/hospitalization. The MACE rate at 1 year was positively related to the number of atherothrombotic anatomic sites in diabetic patients and nondiabetic subjects, and the rate was higher in those with (3.8%) than without (3.0%, p
TL;DR: The prevalence of SDB in active NFL players was modest, predominately mild, and positively associated with several measures of adiposity, and did not account for excess cardiovascular risk factors.
Abstract: A 1994 NATIONAL INSTITUTE FOR OCCUPATIONAL SAFETY AND HEALTH REPORT CONCLUDED THAT THE 6848 RETIRED PROFESSIONAL FOOTBALL PLAYERS studied were 46% less likely to die in middle-age, as compared with a general population of similarly aged men1 Linemen, however, were noted to be at 50% greater risk of death due to heart disease than the general population and at a 37 times higher risk when compared with non-linemen who were retired These findings provided an impetus for wide-ranging studies to better determine the prevalence of cardiovascular disease (CVD) risk factors and disease among active and retired National Football League (NFL) players
A number of factors—including obesity, hypertension, impaired glucose tolerance, and lipid abnormalities—have been implicated in the pathogenesis of increased cardiovascular death among former linemen A recent study has confirmed a near 2-fold increase in the metabolic syndrome in former linemen versus non-linemen2 These athletes have echocardiographic changes, with higher wall thickness and larger chamber size, which are correlated with body size and strength training3,4 These findings often persist into retirement and are most striking in retired linemen or retirees with a body mass index (BMI) greater than 35
Over the 15-year period since the National Institute for Occupational Safety and Health report was published, sleep-disordered breathing (SDB) has been identified as being independently associated with death and CVD5–7 The adjusted hazard ratios for all-cause and cardiovascular mortality are a striking 38 (95% confidence interval [CI], 16-9) and 52 (95% CI, 14-192), respectively, in those with severe untreated SDB (respiratory disturbance index [RDI] ≥ 30) compared with those without SDB (RDI < 5) in the 18 years of follow-up of the Wisconsin sleep cohort5 SDB is associated with insulin resistance and glucose intolerance independent of obesity8,9 Population studies have repeatedly shown anthropometric measures, including BMI and neck and waist circumference, to be strong predictors of SDB10,11
Prior research that was limited to individuals from a single NFL team showed that SDB may be more prevalent among players in the NFL, particularly in those that that would be considered to be at high risk for having SDB12 Given this finding and the current trend toward increasing body size in NFL players, this study was undertaken
We sought to characterize the cross-sectional burden of SDB in active NFL athletes and its association with cardiovascular risk Associations of anthropometric measures with SDB were also examined in this population with elevated BMI but variable body composition
TL;DR: Analytical approaches that establish the reclassification of events provide a unique approach and may serve as a quality imaging metric for estimation of improved health outcomes for stress MPS as well as for comparison to other imaging modalities.
Abstract: Objectives We compared analytical approaches to estimate the added value of myocardial perfusion single-photon emission computed tomography (MPS) variables in estimating coronary artery disease (CAD) outcomes. Background Stress MPS markers of regional ischemia are strong estimators of prognosis. Evidence published to date has not compared analytical methods to establish the added value of stress MPS and to define a clinically meaningful approach to detect improve classification of risk. Methods A total of 4,575 patients were consecutively and prospectively enrolled in the Myoview Prognosis Registry. Multivariable Cox proportional hazards model were employed to estimate CAD death or myocardial infarction (MI). Risk reclassification methods were also calculated. Results In risk-adjusted models (including age, sex, presenting symptoms, stress type, CAD history, and risk factors), stress MPS ischemia, rest and post-stress left ventricular ejection fraction (LVEF) (all p Conclusions Stress-induced ischemia is independently predictive of near-term CAD outcomes. Analytical approaches that establish the reclassification of events provide a unique approach and may serve as a quality imaging metric for estimation of improved health outcomes for stress MPS as well as for comparison to other imaging modalities.
TL;DR: Direct assays for both LDL-C and HDL-C provide an acceptable guide for lipid treatment in Framingham Offspring Study participants, and despite higher use of cholesterol-lowering medication in CHD cases, calculated or direct LDL-B values were still well above recommended values in ChD cases.
TL;DR: The Mediterranean dietary pattern is associated with higher HRV, and a 1-unit higher score was significantly associated with 3.9% to 13% higher time and frequency domain HRV parameters.
Abstract: Background—Reduced heart rate variability (HRV), a measure of cardiac autonomic dysfunction, is a risk factor for coronary artery disease. Diet can influence HRV, but this association may be confounded by genetic and environmental factors. Methods and Results—We administered the Willett Food Frequency Questionnaire to 276 middle-aged male twins. We derived a score measuring the extent to which an individual's diet conformed to the Mediterranean diet following a published algorithm. The higher the score, the greater the similarity to the Mediterranean diet. All twins underwent 24-hour ambulatory ECG recording. Time and frequency domain measures of HRV were calculated. Mixed-effects regression was used to partition the association into between- and within-twin pair differences. After adjusting for energy intake, other nutritional factors, shared genes, and common environment, a 1-unit higher score was significantly associated with 3.9% to 13% higher time and frequency domain HRV parameters. Further controll...
TL;DR: It is concluded that, in a representative community sample, measures of TNFalpha activity are associated with insulin resistance, even after accounting for central adiposity and other adipose tissue biomarkers.
Abstract: Tumor necrosis factor alpha (TNFalpha) is a proinflammatory adipokine hypothesized to link obesity with insulin resistance. Functional studies suggest that TNFalpha acts through pathways involving adipokines and fatty acids to induce insulin resistance. We tested the hypothesis that the association of measures of TNFalpha activity with insulin resistance is independent of obesity and adipose tissue biomarkers. We analyzed data from 2131 participants (without diabetes) of the Framingham Offspring Study examination 7. The outcome of interest was insulin resistance, measured using the homeostasis model assessment (HOMA-IR). Tumor necrosis factor alpha activity was measured by plasma tumor necrosis factor alpha receptor 2 (TNFr2) or TNFalpha; possible confounders included adipose tissue biomarkers (plasma adiponectin, resistin, and triglycerides). We used multivariable age- and sex-adjusted linear regression analyses to adjust for waist circumference and for biomarkers individually and simultaneously, and in biomarker-stratified (above and below median) models. We found that TNFr2 was positively associated with HOMA-IR (r = 0.21, P < .0001). In age- and sex-adjusted model, for each increase of 1 standard deviation of TNFr2 (SD = 746 pg/mL), the log (HOMA-IR) value was increased by 0.11 units (P < .0001). Adjustment for waist circumference reduced the TNFr2 beta-coefficient (by about 45%), but the association between TNFr2 and HOMA-IR remained significant (P < .0001). Tumor necrosis factor alpha receptor 2 was still associated to HOMA-IR after adding adiponectin, resistin, and triglycerides (individually and simultaneously). We found similar associations with plasma levels of TNFalpha. We conclude that, in a representative community sample, measures of TNFalpha activity are associated with insulin resistance, even after accounting for central adiposity and other adipose tissue biomarkers.
TL;DR: Habitual dietary ALA intake is inversely associated with plasma sIL-6R concentrations independent of shared genetic and common environmental influences, and lowering sIL -6R may be a mechanism underlying the cardioprotective properties of habitual dietary ALa.
Journal Article•
TL;DR: This study evaluated the potential contribution of 30 novel biomarkers to the 10-year cardiovascular disease risk in 2 population cohorts based on a highly standardized and comprehensive quality control and assurance program implemented on clinical laboratory instruments.
Abstract: Conventional cardiovascular risk assessment is based on traditional risk factors such as serum cholesterol concentrations (cholesterol, HDL cholesterol, LDL cholesterol) and blood pressure levels. It is becoming increasingly clear that the newer laboratory measures may help to refine risk estimates in the general population. In a recent publication of the MONICA5 (Monitoring of Trends and Determinants of Cardiovascular Disease) investigators 1, Blankenberg and colleagues evaluated the potential contribution of 30 novel biomarkers to the 10-year cardiovascular disease risk in 2 population cohorts. These biomarkers were part of the MORGAM (MONICA, Risk, Genetics, Archiving, and Monograph) Biomarker Project and were representative of 9 distinct metabolic processes linked to atherosclerosis 2. They include ( a ) lipid-related biomarkers, ( b ) renal function markers, ( c ) metabolic markers representing glucose and obesity pathways, ( d ) markers of vascular function and neurohumoral activity, ( e ) inflammation markers, ( f ) markers of oxidative stress and antioxidants, ( g ) coagulation markers, ( h ) angiogenesis markers, and ( i ) necrosis markers.
In addition to the inclusion of a large number of biomarkers for assessment, this study was based on a highly standardized and comprehensive quality control and assurance program implemented on clinical laboratory instruments. All analyses were …