A prolonged QT interval is a marker for an increased risk of ventricular tachyarrhythmias. Both endogenous and exogenous sex hormones have been shown to affect the QT interval. Endogenous testosterone and progesterone shorten the action potential, and estrogen lengthens the QT interval. During a single menstrual cycle, progesterone levels, but not estrogen levels, have the dominant effect on ventricular repolarization in women. Studies of menopausal hormone therapy (MHT) in the form of estrogen-alone therapy (ET) and estrogen plus progesterone therapy (EPT) have suggested a counterbalancing effect of exogenous estrogen and progesterone on the QT. Specifically, ET lengthens the QT, whereas EPT has no effect. To date, there are no studies on oral contraception (OC) and the QT interval, and future research is needed. This review outlines the current literature on sex hormones and QT interval, including the endogenous effects of estrogen, progesterone, and testosterone and the exogenous effects of estrogen and progesterone therapy in the forms of MHT and hormone contraception. Further, we review the potential mechanisms and pathophysiology of sex hormones on the QT interval.
Few studies to date have described the prevalence of electrocardiographic (ECG) abnormalities in a biracial middle-aged cohort.
Methods and Results
Participants underwent measurement of traditional risk factors and 12-lead ECGs coded using both Minnesota Code (MC) and Novacode (NC) criteria. Among 2585 participants, of whom 57% were women and 44% were black (mean age 45 years), the prevalence of major and minor abnormalities were significantly higher (all P<0.001) among black men and women compared to whites. These differences were primarily due to higher QRS voltage and ST/T wave abnormalities among blacks. There was also a higher prevalence of Q waves (MC 1-1, 1-2, 1-3) than described by previous studies. These racial differences remained after multivariate adjustment for traditional cardiovascular (CV) risk factors.
Black men and women have a significantly higher prevalence of ECG abnormalities, independent of traditional CV risk factors, than whites in a contemporary cohort middle-aged participants.
Mammographically-detected breast arterial calcifications (BAC) are considered to be an incidental finding without clinical importance since they are not associated with increased risk of breast cancer. The goal of this article is to review existing evidence that the presence of BAC on mammography correlates with several (but not all) traditional cardiovascular disease (CVD) risk factors and with prevalent and incident CVD. Thus, BAC detected during routine mammography is a noteworthy finding that could be valuable in identifying asymptomatic women at increased future CVD risk that may be candidates for more aggressive management. In addition, there are notable differences in measures of subclinical atherosclerosis burden in women (ie, coronary artery calcification) by race/ethnic background, and the same appears to be true for BAC, although data are very limited. Another noteworthy limitation of prior research on BAC is the reliance on absence vs presence of BAC; no study to date has determined gradation of BAC. Further research is thus required to elucidate the role of BAC gradation in the prediction of CVD outcomes and to determine whether adding BAC gradation to prediction models based on traditional risk factors improves classification of CVD risk.
Breast arterial calcification; Cardiovascular disease risk; Cardiovascular risk factors; Risk stratification; Mammography
To delineate the relationship of obesity to airflow obstruction (AO) and respiratory symptoms in adults without a previous diagnosis of chronic obstructive pulmonary disease (COPD).
We analyzed data for potential referents recruited to be healthy controls for an ongoing study of COPD. The potential referents had no prior diagnosis of COPD or healthcare utilization attributed to COPD in the 12 months prior to recruitment. Subjects completed a structured interview and a clinical assessment including body mass index, spirometry, Six Minute Walk Test (SMWT) and the Short Performance Physical Battery (SPPB). We used multiple regression analyses to test the associations of obesity (BMI≥30kg/m2) and smoking with AO (FEV1/FVC ratio<0.7). We also tested the association of obesity with respiratory symptoms and impaired functional capacity (SPPB, SMWT), adjusting for AO.
Of 371 subjects (aged 40–65), 69 (19%) manifested AO. In multivariate analysis, smoking was positively associated with AO (per 10 pack-years, OR 1.24; 95% CI: 1.04 – 1.49), while obesity was negatively associated with AO (OR 0.54; 95% CI: 0.30 – 0.98). Obesity was associated with increased odds of reporting dyspnea on exertion (OR 3.6; 95% CI: 2.0 – 6.4), productive cough (OR 2.5; 95% CI: 1.1 – 6.0), and with decrements in SMWT distance (−67 ± 9meters; 95% CI: −84 to −50m) and SPPB score (OR 1.9; 95% CI: 1.1 – 3.5). None of these outcomes were associated with AO.
Although AO and obesity are both common among adults without an established COPD diagnosis, obesity, but not AO, is linked to a higher risk of reporting dyspnea on exertion, productive cough, and poorer functional capacity.
airflow obstruction; obesity; functional status; health status; dyspnea
Four custom Axiom genotyping arrays were designed for a genome-wide association (GWA) study of 100,000 participants from the Kaiser Permanente Research Program on Genes, Environment and Health. The array optimized for individuals of European race/ethnicity was previously described. Here we detail the development of three additional microarrays optimized for individuals of East Asian, African American, and Latino race/ethnicity. For these arrays, we decreased redundancy of high-performing SNPs to increase SNP capacity. The East Asian array was designed using greedy pairwise SNP selection. However, removing SNPs from the target set based on imputation coverage is more efficient than pairwise tagging. Therefore, we developed a novel hybrid SNP selection method for the African American and Latino arrays utilizing rounds of greedy pairwise SNP selection, followed by removal from the target set of SNPs covered by imputation. The arrays provide excellent genome-wide coverage and are valuable additions for large-scale GWA studies.
Microarray; Genome-wide association study; Coverage; Imputation; Single nucleotide polymorphism; Throughput
To examine whether kidney dysfunction is associated with the type of clinical presentation of coronary heart disease (CHD).
Reduced kidney function increases risk of developing CHD, but it is not known whether it also influences the acuity of clinical presentation, which has important prognostic implications.
We conducted a case-control study of subjects whose first clinical presentation of CHD was either acute myocardial infarction or stable exertional angina between October 2001-December 2003. Glomerular filtration rate (eGFR) before the incident event was estimated using calibrated serum creatinine and the abbreviated MDRD equation. Patient characteristics and use of medications were ascertained from self-report and health plan databases. We used multivariable logistic regression to examine the association of reduced eGFR and CHD presentation.
We studied 803 adults with incident acute myocardial infarction and 419 adults with incident stable exertional angina who had a baseline eGFR ≤130 ml/min/1.73 m2. Mean eGFR was lower among subjects with acute myocardial infarction compared with stable angina. Compared with eGFR 90–130 ml/min/1.73 m2, we found a strong, graded independent association between reduced eGFR and presenting with acute myocardial infarction: adjusted odds ratio (OR) 1.36 (95% CI: 0.99 to 1.86) for eGFR 60–89 ml/min/1.73 m2, OR 1.55 (0.92 to 2.62) for eGFR 45–59 ml/min/1.73 m2 and OR 3.82 (1.55 to 9.46) for eGFR <45 ml/min/1.73 m2 (P<0.001 for trend).
eGFR less than 45 ml/min/1.73 m2 is a strong, independent predictor of presenting with acute myocardial infarction versus stable angina as the initial manifestation of CHD.
angina; myocardial infarction; renal failure; chronic kidney disease; risk factor
The success of genome-wide association studies has paralleled the development of efficient genotyping technologies. We describe the development of a next-generation microarray based on the new highly-efficient Affymetrix Axiom genotyping technology that we are using to genotype individuals of European ancestry from the Kaiser Permanente Research Program on Genes, Environment and Health (RPGEH). The array contains 674,517 SNPs, and provides excellent genome-wide as well as gene-based and candidate-SNP coverage. Coverage was calculated using an approach based on imputation and cross validation. Preliminary results for the first 80,301 saliva-derived DNA samples from the RPGEH demonstrate very high quality genotypes, with sample success rates above 94% and over 98% of successful samples having SNP call rates exceeding 98%. At steady state, we have produced 462 million genotypes per week for each Axiom system. The new array provides a valuable addition to the repertoire of tools for large scale genome-wide association studies.
Microarray; Genome-wide association study; Coverage; Throughput; Single nucleotide polymorphism
The metabolic syndrome (MetS) is defined as concomitant disorders of lipid and glucose metabolism, central obesity, and high blood pressure, with an increased risk of type 2 diabetes and cardiovascular disease. This study tests whether common genetic variants with pleiotropic effects account for some of the correlated architecture among five metabolic phenotypes that define MetS.
RESEARCH DESIGN AND METHODS
Seven studies of the STAMPEED consortium, comprising 22,161 participants of European ancestry, underwent genome-wide association analyses of metabolic traits using a panel of ∼2.5 million imputed single nucleotide polymorphisms (SNPs). Phenotypes were defined by the National Cholesterol Education Program (NCEP) criteria for MetS in pairwise combinations. Individuals exceeding the NCEP thresholds for both traits of a pair were considered affected.
Twenty-nine common variants were associated with MetS or a pair of traits. Variants in the genes LPL, CETP, APOA5 (and its cluster), GCKR (and its cluster), LIPC, TRIB1, LOC100128354/MTNR1B, ABCB11, and LOC100129150 were further tested for their association with individual qualitative and quantitative traits. None of the 16 top SNPs (one per gene) associated simultaneously with more than two individual traits. Of them 11 variants showed nominal associations with MetS per se. The effects of 16 top SNPs on the quantitative traits were relatively small, together explaining from ∼9% of the variance in triglycerides, 5.8% of high-density lipoprotein cholesterol, 3.6% of fasting glucose, and 1.4% of systolic blood pressure.
Qualitative and quantitative pleiotropic tests on pairs of traits indicate that a small portion of the covariation in these traits can be explained by the reported common genetic variants.
We sought to quantify the impact of respiratory muscle and lower extremity strength on exercise capacity and lower extremity function in patients with chronic obstructive pulmonary disease (COPD).
In 828 persons with COPD, we assessed the impact of reduced respiratory (maximum inspiratory pressure, MIP) and lower extremity muscle strength (quadriceps, QS) on exercise capacity (6 Minute Walk Distance, 6MWT) and lower extremity function (LEF, Short Physical Performance Battery). Multiple regression analyses taking into account key covariates, including lung function and smoking, tested the associations between muscle strength and exercise and functional capacity.
For each ½ standard deviation (0.5 SD) decrement in QS, men walked 18.3 meters less during 6MWT (95% CI −24.1 to −12.4); women 25.1 meters less (95% CI −31.1 to −12.4). For each 0.5 SD decrement in MIP, men walked 9.4 meters less during 6MWT (95% CI – 15.2 to −3.6); women 8.7 meters less (95% CI −14.1 to −3.4). For each 0.5 SD decrease in QS, men had a 1.32 higher odds (95% CI: 1.11 to 1.15) of poor LEF; women, 1.87 higher odds (95% CI: 1.54 to 2.27). Lower MIP (per 0.5 SD) was associated with increased odds of poor LEF in women (OR 1.18, 95% CI: 1.00 to 1.39), but not in men (OR 1.10, 95% CI: 0.93 to 1.31).
In COPD, reduced respiratory and lower extremity muscle strength are associated with decreased exercise and functional capacity. Muscle weakness is likely an important component of impairment and disability in patients with COPD.
Respiratory and skeletal muscle; chronic obstructive pulmonary disease; exercise capacity; lower extremity function
We sought to replicate the association between the kinesin-like protein 6 (KIF6) Trp719Arg polymorphism (rs20455) and clinical coronary artery disease (CAD).
Recent prospective studies suggest that carriers of the 719Arg allele in KIF6 are at increased risk of clinical CAD compared with non-carriers.
The KIF6 Trp719Arg polymorphism (rs20455) was genotyped in nineteen case-control studies of non-fatal CAD either as part of a genome-wide association study or in a formal attempt to replicate the initial positive reports.
Over 17 000 cases and 39 000 controls of European descent as well as a modest number of South Asians, African Americans, Hispanics, East Asians, and admixed cases and controls were successfully genotyped. None of the nineteen studies demonstrated an increased risk of CAD in carriers of the 719Arg allele compared with non-carriers. Regression analyses and fixed effect meta-analyses ruled out with high degree of confidence an increase of ≥2% in the risk of CAD among European 719Arg carriers. We also observed no increase in the risk of CAD among 719Arg carriers in the subset of Europeans with early onset disease (<50 years of age for males and <60 years for females) compared with similarly aged controls as well as all non-European subgroups.
The KIF6 Trp719Arg polymorphism was not associated with the risk of clinical CAD in this large replication study.
kinesin-like protein 6; KIF6; coronary artery disease; myocardial infarction; polymorphism
Patients with chronic kidney disease (CKD) are less likely to receive cardiovascular medications. It is unclear whether differential cardiovascular drug use explains, in part, the excess risk of cardiovascular events and death in patients with CKD and coronary heart disease (CHD).
The ADVANCE Study enrolled patients with new onset CHD (2001-2003) who did (N = 159) or did not have (N = 1088) CKD at entry. The MDRD equation was used to estimate glomerular filtration rate (eGFR) using calibrated serum creatinine measurements. Patient characteristics, medication use, cardiovascular events and death were ascertained from self-report and health plan electronic databases through December 2008.
Post-CHD event ACE inhibitor use was lower (medication possession ratio 0.50 vs. 0.58, P = 0.03) and calcium channel blocker use higher (0.47 vs. 0.38, P = 0.06) in CKD vs. non-CKD patients, respectively. Incidence of cardiovascular events and death was higher in CKD vs. non-CKD patients (13.9 vs. 11.5 per 100 person-years, P < 0.001, respectively). After adjustment for patient characteristics, the rate of cardiovascular events and death was increased for eGFR 45-59 ml/min/1.73 m2 (hazard ratio [HR] 1.47, 95% CI: 1.10 to 2.02) and eGFR < 45 ml/min/1.73 m2 (HR 1.58, 95% CI: 1.00 to 2.50). After further adjustment for statins, β-blocker, calcium channel blocker, ACE inhibitor/ARB use, the association was no longer significant for eGFR 45-59 ml/min/1.73 m2 (HR 0.82, 95% CI: 0.25 to 2.66) or for eGFR < 45 ml/min/1.73 m2 (HR 1.19, 95% CI: 0.25 to 5.58).
In adults with CHD, differential use of cardiovascular medications may contribute to the higher risk of cardiovascular events and death in patients with CKD.
Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a predictor of cardiovascular events that has been shown to vary with race. The objective of this study was to examine factors associated with this racial variation.
We measured Lp-PLA2 mass and activity in 714 healthy older adults with no clinical coronary heart disease and not taking dyslipidemia medication. We evaluated the association between race and Lp-PLA2 mass and activity levels after adjustment for various covariates using multivariable linear regression. These covariates included age, sex, diabetes, hypertension, body mass index, lipid measurements, C-reactive protein, smoking status, physical activity, diet, income, and education level. We further examined genetic covariates that included three single nucleotide polymorphisms shown to be associated with Lp-PLA2 activity levels.
The mean age was 66 years. Whites had the highest Lp-PLA2 mass and activity levels, followed by Hispanics and Asians, and then African-Americans; in age and sex adjusted analyses, these differences were significant for each non-White race as compared to Whites (p < 0.0001). For example, African-Americans were predicted to have a 55.0 ng/ml lower Lp-PLA2 mass and 24.7 nmol/ml-min lower activity, compared with Whites, independent of age and sex (p < 0.0001). After adjustment for all covariates, race remained significantly correlated with Lp-PLA2 mass and activity levels (p < 0.001) with African-Americans having 44.8 ng/ml lower Lp-PLA2 mass and 17.3 nmol/ml-min lower activity compared with Whites (p < 0.0001).
Biological, lifestyle, demographic, and select genetic factors do not appear to explain variations in Lp-PLA2 mass and activity levels between Whites and non-Whites, suggesting that Lp-PLA2 mass and activity levels may need to be interpreted differently for various races.
Angiogenesis is up-regulated in myocardial ischemia. However, limited data exist assessing the value of circulating angiogenic biomarkers in predicting future incidence of acute myocardial infarction (AMI). Our aim was to examine the association between circulating levels of markers of angiogenesis with risk of incident acute myocardial infarction (AMI) in men and women.
We performed a case-control study (nested within a large cohort of persons receiving care within Kaiser Permanente of Northern California) including 695 AMI cases and 690 controls individually matched on age, gender and race/ethnicity.
Median [inter-quartile range] serum concentrations of vascular endothelial growth factor-A (VEGF-A; 260  vs. 235  pg/mL; p = 0.01) and angiopoietin-2 (Ang-2; 1.18 [0.66] vs. 1.05 [0.58] ng/mL; p < 0.0001) were significantly higher in AMI cases than in controls. By contrast, endothelium-specific receptor tyrosine kinase (Tie-2; 14.2 [3.7] vs. 14.0 [3.1] ng/mL; p = 0.07) and angiopoietin-1 levels (Ang-1; 33.1 [13.6] vs. 32.5 [12.7] ng/mL; p = 0.52) did not differ significantly by case-control status. After adjustment for educational attainment, hypertension, diabetes, smoking, alcohol consumption, body mass index, LDL-C, HDL-C, triglycerides and C-reactive protein, each increment of 1 unit of Ang-2 as a Z score was associated with 1.17-fold (95 percent confidence interval, 1.02 to 1.35) increased odds of AMI, and the upper quartile of Ang-2, relative to the lowest quartile, was associated with 1.63-fold (95 percent confidence interval, 1.09 to 2.45) increased odds of AMI.
Our data support a role of Ang-2 as a biomarker of incident AMI independent of traditional risk factors.
angiogenesis; acute myocardial infarction; epidemiology
COPD is a major cause of disability, but little is known about how disability develops in this condition.
We analyzed data from the FLOW (Function, Living, Outcomes, and Work) Study which enrolled 1,202 Kaiser Permanente Northern California members with COPD at baseline and re-evaluated 1,051 subjects at 2 year follow-up. We tested the specific hypothesis that the development of specific non-respiratory impairments (abnormal body composition and muscle strength) and functional limitations (decreased lower extremity function, poor balance, mobility-related dyspnea, reduced exercise performance, and decreased cognitive function) will determine the risk of disability in COPD, after controlling for respiratory impairment (FEV1 and oxygen saturation). The Valued Life Activities Scale was used to assess disability in terms of a broad range of daily activities. The primary disability outcome measure was defined as an increase in the proportion of activities that cannot be performed of 3.3% or greater from baseline to 2-year follow-up (the estimated minimal important difference). Multivariable logistic regression was used for analysis.
Respiratory impairment measures were related to an increased prospective risk of disability (multivariate OR 1.75; 95% CI 1.26 to 2.44 for 1 litre decrement of FEV1 and OR 1.57 per 5% decrement in oxygen saturation; 95% CI 1.13 to 2.18). Non-respiratory impairment (body composition and lower extremity muscle strength) and functional limitations (lower extremity function, exercise performance, and mobility-related dyspnea) were all associated with an increased longitudinal risk of disability after controlling for respiratory impairment (p<0.05 in all cases). Non-respiratory impairment and functional limitations were predictive of prospective disability, above-and-beyond sociodemographic characteristics, smoking status, and respiratory impairment (area under the receiver operating characteristic curve increased from 0.65 to 0.75; p<0.001).
Development of non-respiratory impairment and functional limitations, which reflect the systemic nature of COPD, appear to be critical determinants of disablement. Prevention and treatment of disability require a comprehensive approach to the COPD patient.
Psychological functioning is an important determinant of health outcomes in chronic lung disease. To better define the role of anxiety in COPD, we studied the inter-relations between anxiety and COPD in a large cohort of COPD subjects and a matched control group.
We used data from the FLOW (Function, Living, Outcomes, and Work) cohort (n=1,202) of COPD and matched controls (n=302) without COPD. Anxiety was measured using the Anxiety subscale of the Hospital Anxiety and Depression Scale.
COPD was associated with a greater risk of anxiety in multivariable analysis (OR 1.85; 95% CI 1.072 to 3.18). Among patients with COPD, anxiety was related to poorer health outcomes including worse submaximal exercise performance (less distance walked during the Six Minute Walk Test: -66.3 feet for anxious vs. non-anxious groups; 95% CI -127.3 to -5.36 feet) and a greater risk of self-reported functional limitations (OR 2.41; 95% CI 1.71 to 3.41). COPD subjects with anxiety had a higher longitudinal risk of COPD exacerbation in Cox proportional hazards analysis after controlling for covariates (HR 1.39; 95% CI 1.007 to 1.90).
COPD is associated with a higher risk of anxiety. Once anxiety develops among COPD patients, it is related to poorer health outcomes. Further research is needed to determine whether systematic screening and treatment of anxiety in COPD will improve health outcomes and prevent functional decline and disability.
Although COPD is a common cause of death and disability, little is known about the effects of socioeconomic status (SES) and race-ethnicity on health outcomes.
We aimed to determine the independent impacts of SES and race-ethnicity on COPD severity status, functional limitations, and acute exacerbations of COPD among patients with access to health care. Data were used from the FLOW cohort study of 1,202 Kaiser Permanente Northern California Medical Care Plan members with COPD.
Lower educational attainment and household income were consistently related to greater disease severity, poorer lung function, and greater physical functional limitations in cross-sectional analysis. Black race was associated with greater COPD severity, but these differences were no longer apparent after controlling for SES variables and other covariates (comorbidities, smoking, body mass index, and occupational exposures). Both lower education and income were independently related to a greater prospective risk of acute COPD exacerbation (HR 1.5; 95% CI 1.01 to 2.1; and HR 2.1; 95% CI 1.4 to 3.4, respectively).
Low SES is a risk factor for a broad array of adverse COPD health outcomes. Clinicians and disease management programs should consider SES as a key patient-level marker of risk for poor outcomes.
Our objective was to assess associations between passive smoke exposure in various venues and serum carotenoid concentrations.
CARDIA is an ongoing longitudinal study of the risk factors for subclinical and clinical cardiovascular disease. At baseline in 1985/1986, serum carotenoids were assayed and passive smoke exposure inside and outside of the home and diet were assessed by self-report. Our analytic sample consisted of 2,633 black and white non-smoking adults aged 18–30 years.
Greater total passive smoke exposure was associated with lower levels of the sum of the three provitamin A carotenoids, α-carotene, β-carotene, and β-cryptoxanthin (–0.048 nmol/l per hour of passive smoke exposure, p = 0.001), unassociated with lutein/zeaxanthin, and associated with higher levels of lycopene (0.027 nmol/l per hour of passive smoke exposure, p = 0.010) after adjustment for demographics, diet, lipid profile, and supplement use. Exposure in both home and non-home spaces was also associated with lower levels of the provitamin A carotenoid index.
Cross-sectionally, in 1985/86, passive smoke exposure in various venues was associated with reduced levels of provitamin A serum carotenoids.
Carotenoids; Micronutrients; Occupational health; Passive smoking; Smoke exposure; Tobacco smoke pollution
Coronary wall cardiovascular magnetic resonance (CMR) is a promising noninvasive approach to assess subclinical atherosclerosis, but data are limited in subjects over 60 years old, who are at increased risk. The purpose of the study was to evaluate coronary wall CMR in an asymptomatic older cohort.
Cross-sectional images of the proximal right coronary artery (RCA) were acquired using spiral black-blood coronary CMR (0.7 mm resolution) in 223 older, community-based patients without a history of cardiovascular disease (age 60-72 years old, 38% female). Coronary measurements (total vessel area, lumen area, wall area, and wall thickness) had small intra- and inter-observer variabilities (r = 0.93~0.99, all p < 0.0001), though one-third of these older subjects had suboptimal image quality. Increased coronary wall thickness correlated with increased coronary vessel area (p < 0.0001), consistent with positive remodeling. On multivariate analysis, type 2 diabetes was the only risk factor associated with increased coronary wall area and thickness (p = 0.03 and p = 0.007, respectively). Coronary wall CMR measures were also associated with coronary calcification (p = 0.01-0.03).
Right coronary wall CMR in asymptomatic older subjects showed increased coronary atherosclerosis in subjects with type 2 diabetes as well as coronary calcification. Coronary wall CMR may contribute to the noninvasive assessment of subclinical coronary atherosclerosis in older, at-risk patient groups.
Several studies have shown an association between chronic obstructive pulmonary disease (COPD) and cognitive impairment. These studies have been limited by methodological issues such as diagnostic uncertainty, cross-sectional design, small sample size, or lack of appropriate referent group. This study aimed to elucidate the association between COPD and the risk of cognitive impairment compared to referent subjects without COPD. In patients with established COPD, we evaluated the impact of disease severity and impairment of respiratory physiology on cognitive impairment and the potential mitigating role of oxygen therapy.
We used the Function, Living, Outcomes and Work (FLOW) cohort study of adults with COPD (n = 1202) and referent subjects matched by age, sex, and race (n = 302) to study the potential risk factors for cognitive impairment among subjects with COPD. Cognitive impairment was defined as a Mini-Mental State Exam score of <24 points. Disease severity was using Forced Expiratory Volume in one second (FEV1); the validated COPD Severity Score; and the BMI (Body Mass Index), Obstruction, Dyspnea, Exercise Capacity (BODE) Index. Multivariable analysis was used to control for confounding by age, sex, race, educational attainment, and cigarette smoking.
COPD was associated with a substantive risk of cognitive impairment compared to referent subjects (odds ratio [OR] 2.42; 95% confidence interval [CI] 1.043–6.64). Among COPD patients, none of the COPD severity measures were associated with the risk of cognitive impairment (P > 0.20 in all cases). Low baseline oxygen saturation was related to increased risk of cognitive impairment (OR for oxygen saturation ≤88% (OR 5.45; 95% CI 1.014–29.2; P = 0.048). Conversely, regular use of supplemental oxygen therapy decreased the risk for cognitive impairment (OR 0.14; 95% CI 0.07–0.27; P < 0.0001).
COPD is a major risk factor for cognitive impairment. Among patients with COPD, hypoxemia is a major contributor and regular use of home oxygen is protective. Health care providers should consider screening their COPD patients for cognitive impairment.
chronic obstructive pulmonary disease
Prior research on the risk of depression in COPD has yielded conflicting results. Furthermore, we have an incomplete understanding of how much depression versus respiratory factors contribute to poor health-related quality of life.
Among 1202 adults with COPD and 302 demographically-matched referents without COPD, depressive symptoms were assessed using the 15-item Geriatric Depression Score (GDS). We measured COPD severity using a multifaceted approach, including spirometry, dyspnea, and exercise capacity. We used the Airway Questionnaire 20 and the Physical Component Summary Score to assess respiratory-specific and overall physical quality of life, respectively.
In multivariate analysis adjusting for potential confounders including sociodemographics and all examined comorbidities, COPD subjects were at higher risk for depressive symptoms (GDS≥6) than referents (odds ratio [OR], 3.6; 95% confidence interval [CI], 2.1 – 6.1; p<.001). Stratifying COPD subjects by degree of obstruction on spirometry, all subgroups were at increased risk of depressive symptoms relative to referents (p<.001 for all). In multivariate analysis controlling for COPD severity as well as sociodemographics and comorbidities, depressive symptoms were strongly associated with worse respiratory-specific quality of life (OR, 3.6; 95% CI 2.7 – 4.8; p<.001) and worse overall physical quality of life (OR, 2.4; 95% CI, 1.8 – 3.2; p<.001).
Patients with COPD are at significantly higher risk of having depressive symptoms than referents. Such symptoms are strongly associated with worse respiratory-specific and overall physical health-related quality of life, even after taking COPD severity into account.
Depression; Health Status; Pulmonary Disease; Chronic Obstructive; Quality of Life
Whether cardiorespiratory fitness relates to early subclinical atherosclerotic vascular disease remains unknown. We investigated the relation of cardiorespiratory fitness to coronary artery calcification (CAC) in 2373 African-American and White young adults from the Coronary Artery Risk Development in Young Adults (CARDIA) Study. We measured cardiorespiratory fitness in 1985-1986 (baseline) using a symptom-limited exercise test on a treadmill. Coronary calcium scores were measured in 2001-2002 (year 15) using electron-beam or multi-detector computed tomography. CAC was classified as present or absent, while cardiorespiratory fitness was classified as sex-specific low, moderate, and high fitness categories. After adjustment for age, sex, race, clinical center, education, cigarette smoking, waist girth, alcohol intake, physical activity, systolic blood pressure, antihypertensive medication use, diabetes mellitus, and fasting insulin, baseline cardiorespiratory fitness was inversely associated with prevalence of CAC in young adults (P for trend = 0.03). The odds ratios of having CAC for persons in the moderately and highly fit individuals were 0.80 (95% confidence interval (CI), 0.55-1.15) and 0.59 (95% CI, 0.36-0.97), respectively, as compared with the low-fit individuals. High levels of cardiorespiratory fitness were associated with a lower risk of having coronary calcification 15 years later in African-American and White young adults.
Coronary artery calcification; Cardiorespiratory fitness; Physical activity
Background: Limited data suggest that moderate alcohol drinkers may have better lung airways function than abstainers. Because few studies have fully accounted for confounders (including smoking and coronary disease), and some might have been biased by the inclusion with nondrinkers of alcohol drinkers who quit because of illness, we performed a cross-sectional analysis in a large free-living population.
Methods: We studied the relation between alcohol and airways function in 177,721 members of a comprehensive health plan. An item on a questionnaire administered as part of a health examination asked for “usual number of drinks in the past year.” Respondents were asked to lump “wine, beer, whiskey, and cocktails” together. Health history queries included 47 items indicative of possible cardiorespiratory (CR) illness; participants with one or more positive response (61.0%) were classified as “CR yes.” Lung function measurements were part of the health examination; we studied one-second forced expiratory volume (FEV1), forced vital capacity (FVC), and FEV1/FVC by analysis of covariance and FEV1/FVC <0.7 by logistic regression. Nondrinkers were the referent for alcohol categories; covariates were age, sex, ethnicity, smoking, education, body mass index, and CR composite yes/no.
Results: For each measure studied, persons reporting two or fewer drinks per day or three to five drinks per day had better airways function than nondrinkers (p < 0.001), but heavier drinkers had worse function. This J-shaped relation was consistent across multiple strata, including CR “yes” or “no.”
Conclusion: Independent of smoking and evident lung or heart disease, light to moderate drinkers of alcohol had better FEV1, FVC, and FEV1/FVC than abstainers did. Although this association does not prove causality, drinking moderate amounts of alcoholic beverages may have some benefit for lung function.
Few cohort studies have focused on risk factors for end-stage renal disease (ESRD). This investigation evaluated the prognostic value of several potential novel risk factors for ESRD after considering established risk factors.
We studied 177 570 individuals from a large integrated health care delivery system in northern California who volunteered for health checkups between June 1, 1964, and August 31, 1973. Initiation of ESRD treatment was ascertained using US Renal Data System registry data through December 31, 2000.
A total of 842 cases of ESRD were observed during 5 275 957 person-years of follow-up. This comprehensive evaluation confirmed the importance of established risk factors, including the following: male sex, older age, proteinuria, diabetes mellitus, lower educational attainment, and African American race, as well as higher blood pressure, body mass index, and serum creatinine level. The 2 most potent risk factors were proteinuria and excess weight. For proteinuria, the adjusted hazard ratios (HRs) were 7.90 (95% confidence interval [CI], 5.35–11.67) for 3 to 4+ on urine dipstick, 3.59 (2.82–4.57) for 1 to 2+ on urine dipstick, and 2.37 (1.79–3.14) for trace vs negative on urine dipstick. For excess weight, the HRs were 4.39 (95% CI, 3.38–5.70) for class 2 to class 3 obesity, 3.11 (2.51–3.84) for class 1 obesity, and 1.65 (1.39–1.97) for overweight vs normal weight. Furthermore, several independent novel risk factors for ESRD were identified, including lower hemoglobin level (1.33 [1.08–1.63] for lowest vs highest quartile), higher serum uric acid level (2.14 [1.65–2.77] for highest vs lowest quartile), self-reported history of nocturia (1.36 [1.17–1.58]), and family history of kidney disease (HR, 1.40 [95% CI, 1.02–1.90]).
We confirmed the importance of established ESRD risk factors in this large cohort with broad sex and racial/ethnic representation. Lower hemoglobin level, higher serum uric acid level, self-reported history of nocturia, and family history of kidney disease are independent risk factors for ESRD.
Genome-wide SNP analyses reveal the admixed African genetic ancestry of African Americans.
Accurate, high-throughput genotyping allows the fine characterization of genetic ancestry. Here we applied recently developed statistical and computational techniques to the question of African ancestry in African Americans by using data on more than 450,000 single-nucleotide polymorphisms (SNPs) genotyped in 94 Africans of diverse geographic origins included in the HGDP, as well as 136 African Americans and 38 European Americans participating in the Atherosclerotic Disease Vascular Function and Genetic Epidemiology (ADVANCE) study. To focus on African ancestry, we reduced the data to include only those genotypes in each African American determined statistically to be African in origin.
From cluster analysis, we found that all the African Americans are admixed in their African components of ancestry, with the majority contributions being from West and West-Central Africa, and only modest variation in these African-ancestry proportions among individuals. Furthermore, by principal components analysis, we found little evidence of genetic structure within the African component of ancestry in African Americans.
These results are consistent with historic mating patterns among African Americans that are largely uncorrelated to African ancestral origins, and they cast doubt on the general utility of mtDNA or Y-chromosome markers alone to delineate the full African ancestry of African Americans. Our results also indicate that the genetic architecture of African Americans is distinct from that of Africans, and that the greatest source of potential genetic stratification bias in case-control studies of African Americans derives from the proportion of European ancestry.