Androgenicity in Young Women and Development of Metabolic Syndrome Before Menopause: The CARDIA and CARDIA Women's Studies.

Context: There are no reported data from prospective long-term studies on the relation of androgen levels in young women with development of metabolic syndrome (MetS) before menopause. Objective: We investigated associations of androgens and SHBG with incident MetS during 23 years of follow-up. Methods: We included 366 White and 375 Black women ages 20 to 32 years participating in the CARDIA study and CARDIA Women's study, free of MetS at baseline examination (1987-1988), and premenopausal 23 years later. Androgens and SHBG were categorized into quartiles. MetS was defined according to the American Heart Association/National Heart, Lung, and Blood Institute 2009 Joint Scientific Statement. Cox proportional hazards models were used. Results: By year 23, 30% of women developed MetS. Adjusting for baseline age, race, and education, hazard ratios (95% CI) of developing MetS were 1.46 (1.02-2.10) and 2.22 (1.53-3.21) for women in the highest vs lowest total testosterone (T) and free T quartile, respectively. The hazards of developing MetS were 47%, 59%, and 53% lower for women with SHBG in the second, third, and fourth quartiles (vs lowest quartile), respectively. Associations were attenuated for total T with further adjustments for smoking, physical activity, menstrual status, oral contraceptive/hormone (OCHM) use, insulin level, oligomenorrhea, and age at menarche, but remained statistically significant for free T and SHBG. Associations were similar for both Blacks and Whites, and OCHM nonusers, but not for OCHM users. Conclusion: High androgenicity in young premenopausal women is associated with higher risk of future MetS, suggesting that early assessment of androgens may contribute to prevention.

Clinical research training and capacity building for prevention and control of non-communicable diseases: A programme in India.

BACKGROUND.: Non-communicable diseases (NCDs)-a term which includes diabetes, cardiovascular disease, cancers, chronic respiratory diseases, and mental illness-are now the major cause of death in India and pose healthcare and economic challenges. There is an urgent need for enhanced clinical research training and capacity building for NCD prevention and control in India. METHODS.: We describe a multi-pronged approach funded in part by the US National Institutes of Health Fogarty International Center, which was initiated in 2001, to train Indian present and future scientists/doctors in NCD prevention and control. The approaches used were annual national seminars, intensive training courses, in-house workshops, short-term training sessions in the USA and monthly video conferences. RESULTS.: During 2001-2016, a total of 3650 undergraduate, postgraduate and faculty from medical colleges and institutes from almost all states in India and several neighbouring countries participated in seminars and other capacity-building workshops held at the Madras Diabetes Research Foundation, Chennai and at six other medical colleges; 883 delegates participated in the in-house workshops, 463 in the intensive interactive sessions; 244 in workshops on advanced techniques in genomics; and 37 in short-term training sessions held in the USA. CONCLUSION.: Through this unique capacity-building programme, more than 5000 individuals representing faculty and students from various medical colleges and research institutes across, and beyond, India, underwent training in the prevention and control of NCDs.

Prospective association of polycystic ovary syndrome with coronary artery calcification and carotid-intima-media thickness: the Coronary Artery Risk Development in Young Adults Women's study.

OBJECTIVE: To study the independent associations of polycystic ovary syndrome (PCOS), and its 2 components, hyperandrogenism and anovulation, with coronary artery calcification (CAC) and carotid artery intima-media thickness (IMT). APPROACH AND RESULTS: At the year 20 of the Coronary Artery Risk Development in Young Adults (CARDIA) study, a population-based multicenter cohort of young adults, women (mean age, 45 years) with information on menses and hirsutism in their twenties were assessed for CAC (n=982) and IMT (n=988). We defined PCOS as women who had both irregular menses and hyperandrogenism (n=55); isolated oligomenorrhea (n=103) as women who only had irregular menses; and isolated hyperandrogenism (n=156) as women who had either hirsutism or increased testosterone levels. Logistic regressions and general linear models were used to estimate the associations between components of PCOS and subclinical CVD. The prevalence of CAC was 10.3% overall. Women with PCOS had a multivariable adjusted odds ratio of 2.70 (95% confidence interval, 1.31-5.60) for CAC. Women with either isolated oligomenorrhea or isolated hyperandrogenism had no increased risk of CAC when compared with unexposed women. Women with PCOS had significantly increased bulb and internal carotid-IMT measurements; however, no significant differences were noted in bulb or internal carotid artery IMT among women with either isolated oligomenorrhea or isolated hyperandrogenism when compared with unexposed women. There were no differences in common carotid-IMT among the 4 study groups. CONCLUSIONS: In this study, women with PCOS, manifested as both anovulation and hyperandrogenism, but not women with one of these manifestations alone, were at increased risk for the development of subclinical CVD.

Risk factors for osteonecrosis of the jaws: a case-control study from the CONDOR Dental PBRN.

Case reports and cohort studies have linked bisphosphonate therapy and osteonecrosis of the jaws (ONJ), but neither causality nor specific risks for lesion development have been clearly established. We conducted a 1:3 case-control study with 3 dental practice-based research networks, using dentist questionnaires and patient interviews for collection of data on bisphosphonate therapy, demographics, co-morbidities, and dental and medical treatments. Multivariable logistic regression analyses tested associations between bisphosphonate use and other risk factors with ONJ. We enrolled 191 ONJ cases and 573 controls in 119 dental practices. Bisphosphonate use was strongly associated with ONJ (odds ratios [OR] 299.5 {95% CI 70.0-1282.7} for intravenous [IV] use and OR = 12.2 {4.3-35.0} for oral use). Risk markers included local suppuration (OR = 7.8 {1.8-34.1}), dental extraction (OR = 7.6 {2.4-24.7}), and radiation therapy (OR = 24.1 {4.9-118.4}). When cancer patients (n = 143) were excluded, bisphosphonate use (OR = 7.2 {2.1-24.7}), suppuration (OR = 11.9 {2.0-69.5}), and extractions (OR = 6.6 {1.6-26.6}) remained associated with ONJ. Higher risk of ONJ began within 2 years of bisphosphonate initiation and increased 4-fold after 2 years. Both IV and oral bisphosphonate use were strongly associated with ONJ. Duration of treatment >2 years; suppuration and dental extractions were independent risk factors for ONJ.

Polycystic ovary syndrome is associated with higher left ventricular mass index: the CARDIA women's study.

OBJECTIVE: The aim of the study was to determine whether young women with polycystic ovary syndrome (PCOS) have evidence of early structural changes in echocardiographic parameters as a measurement of cardiovascular risk. METHODS: We investigated the association of PCOS and echocardiographic parameters in 984 black and white women in the Coronary Artery Risk Development in Young Adults (CARDIA) study, a cohort followed prospectively for 20 yr. Women ages 34-46 (Year 16) completed questionnaires recalling symptoms of oligomenorrhea and hirsutism in their 20s and 30s. Serum androgens were obtained at Year 2. Women in their 20s and 30s were classified into four mutually exclusive groups: 1) PCOS; 2) isolated oligomenorrhea (IO); 3) isolated hyperandrogenism (IH); and 4) reference group. Outcome measures were defined as echocardiography data from Year 5. We used multivariable linear regression models to evaluate the association of PCOS and its components with left ventricular (LV) mass index, left atrial (LA) diameter, LV ejection fraction (LVEF), and mitral inflow early wave to late wave ratio. RESULTS: Among 984 participants, 42 women (4.3%) were classified as PCOS, 67 (6.8%) as IO, and 178 (18.0%) as IH. In multivariable linear regression analyses, women with PCOS had a 3.14 g/m(2.7) (95% confidence interval, 0.48-5.81) higher LV mass index compared to the reference group (approximately 10% higher). PCOS women also had a 0.11 cm/m (95% confidence interval, 0.02-0.19) larger LA diameter, after adjustment for age and race. CONCLUSION: PCOS, but not IO or IH, is associated with a higher LV mass index and larger LA diameter in young women, suggestive of early adverse cardiac remodeling. Additional longitudinal studies are needed to evaluate whether this difference persists over time.

Genome-wide joint meta-analysis of SNP and SNP-by-smoking interaction identifies novel loci for pulmonary function.

Genome-wide association studies have identified numerous genetic loci for spirometic measures of pulmonary function, forced expiratory volume in one second (FEV(1)), and its ratio to forced vital capacity (FEV(1)/FVC). Given that cigarette smoking adversely affects pulmonary function, we conducted genome-wide joint meta-analyses (JMA) of single nucleotide polymorphism (SNP) and SNP-by-smoking (ever-smoking or pack-years) associations on FEV(1) and FEV(1)/FVC across 19 studies (total N = 50,047). We identified three novel loci not previously associated with pulmonary function. SNPs in or near DNER (smallest P(JMA = )5.00×10(-11)), HLA-DQB1 and HLA-DQA2 (smallest P(JMA = )4.35×10(-9)), and KCNJ2 and SOX9 (smallest P(JMA = )1.28×10(-8)) were associated with FEV(1)/FVC or FEV(1) in meta-analysis models including SNP main effects, smoking main effects, and SNP-by-smoking (ever-smoking or pack-years) interaction. The HLA region has been widely implicated for autoimmune and lung phenotypes, unlike the other novel loci, which have not been widely implicated. We evaluated DNER, KCNJ2, and SOX9 and found them to be expressed in human lung tissue. DNER and SOX9 further showed evidence of differential expression in human airway epithelium in smokers compared to non-smokers. Our findings demonstrated that joint testing of SNP and SNP-by-environment interaction identified novel loci associated with complex traits that are missed when considering only the genetic main effects.

Correlates of heart rate recovery over 20 years in a healthy population sample.

INTRODUCTION: Slow HR recovery (HRR) from a graded exercise treadmill test (GXT) is a marker of impaired parasympathetic reactivation that is associated with elevated mortality. Our objective was to test whether demographic, behavioral, or CHD risk factors during young adulthood were associated with the development of slow HRR. METHODS: Participants from the Coronary Artery Risk Development in Young Adults study underwent symptom-limited maximal GXT using a modified Balke protocol at baseline (1985-1986) and 20-yr follow-up (2005-2006) examinations. HRR was calculated as the difference between peak HR and HR 2 min after cessation of the GXT. Slow HRR was defined as 2-min HRR <22 beats·min(-1). RESULTS: In 2730 participants who did not have slow HRR at baseline, mean ± SD HRR was 44 ± 11 beats·min(-1) at baseline and declined to 40 ± 12 beats·min(-1) in 2005-2006; slow HRR developed in 5% (n = 135) of the sample by 2005-2006. Female sex, black race, fewer years of education, obesity, cigarette smoking, higher depressive symptoms, higher fasting glucose, hypertension, metabolic syndrome, and physical inactivity and low fitness were each associated with incident slow HRR. In a multivariable model, higher body mass index, larger waist, low education, fasting glucose, and current smoking remained significantly associated with incident slow HRR. Increasing body mass index (per SD higher) during follow-up and incident hypertension, diabetes, and metabolic syndrome (in the subsets of participants who were free from those conditions at baseline) were each associated with significantly elevated odds of incident slow HRR. CONCLUSIONS: On average, HRR declines with aging; however, the odds of having slow HRR in early middle age is significantly associated with traditional CHD risk factors.

Restoration of noncarious tooth defects by dentists in The Dental Practice-Based Research Network.

BACKGROUND: The authors conducted a study to quantify the reasons for restoring noncarious tooth defects (NCTDs) by dentists in The Dental Practice-Based Research Network (DPBRN) and to assess the tooth, patient and dentist characteristics associated with those reasons. METHODS: Data were collected by 178 DPBRN dentists regarding the placement of 1,301 consecutive restorations owing to NCTDs. Information gathered included the main clinical reason, other than dental caries, for restoration of previously unrestored permanent tooth surfaces; characteristics of patients who received treatment; dentists' and dental practices' characteristics; teeth and surfaces restored; and restorative materials used. RESULTS: Dentists most often placed restorations to treat lesions caused by abrasion, abfraction or erosion (AAE) (46 percent) and tooth fracture (31 percent). Patients 41 years or older received restorations mainly because of AAE (P < .001). Premolars and anterior teeth were restored mostly owing to AAE; molars were restored mostly owing to tooth fracture (P < .001). Dentists used directly placed resin-based composite (RBC) largely to restore AAE lesions and fractured teeth (P < .001). CONCLUSIONS: Among DPBRN practices, AAE and tooth fracture were the main reasons for restoring noncarious tooth surfaces. Pre-molars and anterior teeth of patients 41 years and older are most likely to receive restorations owing to AAE; molars are most likely to receive restorations owing to tooth fracture. Dentists restored both types of NCTDs most often with RBC.

Effect of increasing doses of saw palmetto extract on lower urinary tract symptoms: a randomized trial.

CONTEXT: Saw palmetto fruit extracts are widely used for treating lower urinary tract symptoms attributed to benign prostatic hyperplasia (BPH); however, recent clinical trials have questioned their efficacy, at least at standard doses (320 mg/d). OBJECTIVE: To determine the effect of saw palmetto extract (Serenoa repens, from saw palmetto berries) at up to 3 times the standard dose on lower urinary tract symptoms attributed to BPH. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, multicenter, placebo-controlled randomized trial at 11 North American clinical sites conducted between June 5, 2008, and October 10, 2010, of 369 men aged 45 years or older, with a peak urinary flow rate of at least 4 mL/s, an American Urological Association Symptom Index (AUASI) score of between 8 and 24 at 2 screening visits, and no exclusions. INTERVENTIONS: One, 2, and then 3 doses (320 mg/d) of saw palmetto extract or placebo, with dose increases at 24 and 48 weeks. MAIN OUTCOME MEASURES: Difference in AUASI score between baseline and 72 weeks. Secondary outcomes included measures of urinary bother, nocturia, peak uroflow, postvoid residual volume, prostate-specific antigen level, participants' global assessments, and indices of sexual function, continence, sleep quality, and prostatitis symptoms. RESULTS: Between baseline and 72 weeks, mean AUASI scores decreased from 14.42 to 12.22 points (-2.20 points; 95% CI, -3.04 to -1.36) [corrected]with saw palmetto extract and from 14.69 to 11.70 points (-2.99 points; 95% CI, -3.81 to -2.17) with placebo. The group mean difference in AUASI score change from baseline to 72 weeks between the saw palmetto extract and placebo groups was 0.79 points favoring placebo (upper bound of the 1-sided 95% CI most favorable to saw palmetto extract was 1.77 points, 1-sided P = .91). Saw palmetto extract was no more effective than placebo for any secondary outcome. No clearly attributable adverse effects were identified. CONCLUSION: Increasing doses of a saw palmetto fruit extract did not reduce lower urinary tract symptoms more than placebo. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00603304.

Serum carotenoid concentrations predict lung function evolution in young adults: the Coronary Artery Risk Development in Young Adults (CARDIA) study.

BACKGROUND: A higher dietary intake of carotenoid-rich foods and higher circulating concentrations of carotenoids have been associated with better lung function in cross-sectional studies; however, the longitudinal association between carotenoids and lung function has shown conflicting results. OBJECTIVE: We examined the longitudinal association between serum carotenoids (ß-cryptoxanthin, α-carotene, ß-carotene, lutein/zeaxanthin, and lycopene) and the evolution of lung function. DESIGN: We evaluated our hypothesis in the Coronary Artery Risk Development in Young Adults (CARDIA) prospective cohort study. Spirometry testing was conducted at year 0 (1985-1986) and at follow-up in years 2, 5, 10, and 20; serum carotenoids were assayed at years 0 and 15, and diet was assessed at years 0 and 20. RESULTS: Year 0 sum of provitamin A carotenoids and ß-cryptoxanthin concentrations were associated with maximum forced vital capacity (FVC) (P ≤ 0.01) and forced expiratory volume in 1 s (FEV(1)) (P ≤ 0.05) (maximum across years 0-10) in linear regression models adjusted for age, race, height, study center, amount of physical activity, smoking status, and BMI. Year 0 lutein/zeaxanthin and lycopene were not associated with maximum lung function. Baseline concentrations of lutein/zeaxanthin, lycopene, sum of the 3 provitamin A carotenoids, ß-carotene, and ß-cryptoxanthin were each inversely associated with a decline from maximum FVC and FEV(1) (P ≤ 0.04). The sum of provitamin A carotenoids and lycopene remained significant after adjustment for dietary intake related to serum carotenoids (P ≤ 0.03). The 15-y change in provitamin A carotenoid and lutein/zeaxanthin concentrations was associated with a slower decline from maximum FVC and FEV(1) (P ≤ 0.04). CONCLUSION: These findings support an association between serum carotenoid concentrations and a decline in lung function.

Medication adherence among rural, low-income hypertensive adults: a randomized trial of a multimedia community-based intervention.

PURPOSE: Examine the effectiveness of a community-based, multimedia intervention on medication adherence among hypertensive adults. DESIGN: Randomized controlled trial. SETTING: Rural south Alabama. SUBJECTS: Low-income adults (N  =  434) receiving medication at no charge from a public health department or a Federally Qualified Health Center. INTERVENTION: Both interventions were home-based and delivered via computer by a community health advisor. The adherence promotion (AP) intervention focused on theoretical variables related to adherence (e.g., barriers, decisional balance, and role models). The cancer control condition received general cancer information. MEASURES: Adherence was assessed by pill count. Other adherence-related variables, including barriers, self-efficacy, depression, and sociodemographic variables, were collected via a telephone survey. ANALYSIS: Chi-square analysis tested the hypothesis that a greater proportion of participants in the AP intervention are ≥80% adherent compared to the control group. General linear modeling examined adherence as a continuous variable. RESULTS: Participants receiving the intervention did not differ from individuals in the control group (51% vs. 49% adherent, respectively; p  =  .67). Clinic type predicted adherence (p < .0001), as did forgetting to take medications (p  =  .01) and difficulty getting to the clinic to obtain medications (p < .001). CONCLUSIONS: Multilevel interventions that focus on individual behavior and community-level targets (e.g., how health care is accessed and delivered) may be needed to improve medication adherence among low-income rural residents.

The relationship between lower urinary tract symptom severity and sleep disturbance in the CAMUS trial.

PURPOSE: Bothersome lower urinary tract symptoms, including nocturia, significantly impact general health related quality of life in men, as does sleep disturbance. However, few groups have examined the relationship between urinary symptom severity and sleep disturbance. MATERIALS AND METHODS: Men enrolled in a clinical trial of saw palmetto (Serenoa repens) were studied at baseline. Lower urinary tract symptom severity, as determined by the American Urological Association symptom index and quality of life scores, and the degree of sleep disturbance were determined by the Jenkins sleep scale. Analysis was done, adjusting for baseline characteristics, to identify predictors of severe sleep disturbance. RESULTS: A total of 366 men with a mean ± SD age of 60.9 ± 8.3 years who had moderate-severe lower urinary tract symptoms (mean American Urological Association symptom index score 14.58 ± 4.6 points) and a mean Jenkins sleep score of 7.3 ± 4.7 points were included in analysis. Overall there were significant associations between the American Urological Association symptom index score and sleep disturbance severity. Multivariate analysis revealed that obstructive and irritative symptoms were significantly associated with severe sleep disturbance. Further analysis showed that lower serum prostate specific antigen and post-void residual urine volume were also significantly associated with the degree of sleep disturbance. CONCLUSIONS: Lower urinary tract symptom severity is a risk factor for severe sleep disturbance in men. While nocturia was significantly associated with sleep disturbance, other lower urinary tract symptoms were also independent predictors of sleep dysfunction.

Risk factors for osteonecrosis of the jaws: a case-control study from the CONDOR dental PBRN.

Case reports and cohort studies have linked bisphosphonate therapy and osteonecrosis of the jaws (ONJ), but neither causality nor specific risks for lesion development have been clearly established. We conducted a 1:3 case-control study with three dental Practice-based Research Networks, using dentist questionnaires and patient interviews for collection of data on bisphosphonate therapy, demographics, co-morbidities, and dental and medical treatments. Multivariable logistic regression analyses tested associations between bisphosphonate use and other risk factors with ONJ. We enrolled 191 ONJ cases and 573 controls in 119 dental practices. Bisphosphonate use was strongly associated with ONJ (odds ratios [OR] 299.5 {95%CI 70.0-1282.7} for intravenous [IV] use and OR = 12.2 {4.3-35.0} for oral use). Risk markers included local suppuration (OR = 7.8 {1.8-34.1}), dental extraction (OR = 7.6 {2.4-24.7}), and radiation therapy (OR = 24.1 {4.9-118.4}). When cancer patients (n = 143) were excluded, bisphosphonate use (OR = 7.2 {2.1-24.7}), suppuration (OR = 11.9 {2.0-69.5}), and extractions (OR = 6.6 {1.6-26.6}) remained associated with ONJ. Higher risk of ONJ began within 2 years of bisphosphonate initiation and increased four-fold after 2 years. Both IV and oral bisphosphonate use were strongly associated with ONJ. Duration of treatment > 2 years; suppuration and dental extractions were independent risk factors for ONJ.

Polycystic ovary syndrome and risk for long-term diabetes and dyslipidemia.

OBJECTIVE: To estimate whether women aged 20-32 years who fulfilled National Institutes of Health criteria for polycystic ovary syndrome (PCOS) would be at higher risk for subsequent development of incident diabetes, dyslipidemia, and hypertension, and to estimate whether normal-weight women with PCOS would have the same degree of cardiovascular risk as overweight women with PCOS. METHODS: We estimated the association of PCOS with incident diabetes, dyslipidemia, and hypertension over a period of 18 years among 1,127 white and African-American women in the Coronary Artery Risk Development in Young Adults cohort. We classified women at baseline (ages 20-32 years) based on self-reported symptoms and serum androgen measures using National Institutes of Health PCOS criteria. We estimated the association of PCOS and subsequent cardiovascular risk factors, independent of baseline body mass index (BMI), using multivariable logistic regression. Additionally, among 746 women with a second assessment of PCOS at ages 34-46 years, we estimated the association of persistent PCOS with cardiovascular risk factors. RESULTS: Of 1,127 women, 53 (4.7%) met criteria for PCOS at ages 20-32 years. Polycystic ovary syndrome was associated with a twofold higher odds of incident diabetes (23.1% compared with 13.1%, adjusted odds ratio [AOR] 2.4, confidence interval [CI] 1.2-4.9) and dyslipidemia (41.9% compared with 27.7%, AOR 1.9, CI 1.0-3.6) over the course of 18 years; the association with incident hypertension was not significant (26.9% compared with 26.3%, AOR 1.7, CI 0.8-3.3). Normal-weight women with PCOS (n=31) had a threefold higher odds of incident diabetes compared with normal-weight women without PCOS (AOR 3.1, CI 1.2-8.0). Compared with those without PCOS, women with persistent PCOS (n=11) had the highest odds of diabetes (AOR 7.2, CI 1.1-46.5). CONCLUSION: Polycystic ovary syndrome is associated with subsequent incident diabetes and dyslipidemia, independent of BMI. Diabetes risk may be greatest for women with persistent PCOS symptoms. LEVEL OF EVIDENCE: II.

Geographic and demographic variability in 20-year hypertension incidence: the CARDIA study.

Although the variability of cardiovascular disease mortality by geography, race, and sex is well known, less is known about risk factor variation. We assessed 20-year incidence of hypertension, a cardiovascular disease risk factor, across 4 US urban areas and by race-sex. Among 3436 eligible adults 18 to 30 years of age when recruited in 1985 to 1986 in the community-based Coronary Artery Risk Development in Young Adults (CARDIA) cohort, we examined 20-year cumulative incidence of hypertension (systolic blood pressure ≥ 140 mm Hg or diastolic blood pressure ≥ 90 mm Hg or antihypertensive medication use at any examination) by site and race-sex, adjusting for baseline and time-dependent covariates with Cox regression. Twenty-year incidence, when the mean age was ≈ 45 years, was 34.5% in black men (n = 617), 37.6% in black women (n = 965), 21.4% in white men (n = 856), and 12.3% in white women (n = 998; P<0.001). Incidence was 33.6% in Birmingham, Ala, 23.4% in Chicago, Ill, 19% in Minneapolis, Minn, and 27.4% in Oakland, Calif (P<0.001). After adjustment for age, race, sex, heart rate, body mass index, smoking, family history, education, uric acid, alcohol use, physical activity, and baseline systolic blood pressure, hazard ratios (95% CI) compared with Birmingham were 0.72 (0.59 to 0.87) for Chicago, 0.60 (0.50 to 0.74) for Minneapolis, and 0.73 (0.61 to 0.87) for Oakland. Race-sex differences persisted after adjustment for site, especially for black women. From young adulthood to middle age, hypertension incidence varies significantly across urban areas. Independent of geography, blacks, especially women, are at markedly higher risk of hypertension. Hypertension incidence may contribute to geographic and racial differences in cardiovascular disease mortality, including stroke.

Factors associated with mortality in transplant patients with invasive aspergillosis.

BACKGROUND: Invasive aspergillosis (IA) is an important cause of morbidity and mortality in hematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT) recipients. The purpose of this study was to evaluate factors associated with mortality in transplant patients with IA. METHODS: Transplant patients from 23 US centers were enrolled from March 2001 to October 2005 as part of the Transplant Associated Infection Surveillance Network. IA cases were identified prospectively in this cohort through March 2006, and data were collected. Factors associated with 12-week all-cause mortality were determined by logistic regression analysis and Cox proportional hazards regression. RESULTS: Six-hundred forty-two cases of proven or probable IA were evaluated, of which 317 (49.4%) died by the study endpoint. All-cause mortality was greater in HSCT patients (239 [57.5%] of 415) than in SOT patients (78 [34.4%] of 227; P<.001). Independent poor prognostic factors in HSCT patients were neutropenia, renal insufficiency, hepatic insufficiency, early-onset IA, proven IA, and methylprednisolone use. In contrast, white race was associated with decreased risk of death. Among SOT patients, hepatic insufficiency, malnutrition, and central nervous system disease were poor prognostic indicators, whereas prednisone use was associated with decreased risk of death. Among HSCT or SOT patients who received antifungal therapy, use of an amphotericin B preparation as part of initial therapy was associated with increased risk of death. CONCLUSIONS: There are multiple variables associated with survival in transplant patients with IA. Understanding these prognostic factors may assist in the development of treatment algorithms and clinical trials.

Longitudinal association of body mass index with lung function: the CARDIA study.

BACKGROUND: Lung function at the end of life depends on its peak and subsequent decline. Because obesity is epidemic in young adulthood, we quantified age-related changes in lung function relative to body mass index (BMI). METHODS: The Coronary Artery Risk Development in Young Adults (CARDIA) study in 1985-86 (year 0) recruited 5,115 black and white men and women, aged 18-30. Spirometry testing was conducted at years 0, 2, 5 and 10. We estimated 10 year change in FVC, FEV1 and FEV1/FVC according to baseline BMI and change in BMI within birth cohorts with initial average ages 20, 24, and 28 years, controlling for race, sex, smoking, asthma, physical activity, and alcohol consumption. MEASUREMENTS AND MAIN RESULTS: Participants with baseline BMI < 21.3 kg/m2 experienced 10 year increases of 71 ml in FVC and 60 ml in FEV1 and neither measure declined through age 38. In contrast, participants with baseline BMI > or = 26.4 kg/m2 experienced 10 year decreases of 185 ml in FVC and 64 ml in FEV1. FEV1/FVC increased with increasing BMI. Weight gain was also associated with lung function. Those who gained the most weight over 10 years had the largest decrease in FVC, but FVC increased with weight gain in those initially thinnest. In contrast, FEV1 decreased with increasing weight gain in all participants, with maximum decline in obese individuals who gained the most weight during the study. CONCLUSION: Among healthy young adults, increasing BMI in the initially thin participants was associated with increasing then stable lung function through age 38, but there were substantial lung function losses with higher and increasing fatness. These results suggest that the obesity epidemic threatens the lung health of the general population.

Early adult risk factor levels and subsequent coronary artery calcification: the CARDIA Study.

OBJECTIVES: We sought to determine whether early adult levels of cardiovascular risk factors predict subsequent coronary artery calcium (CAC) better than concurrent or average 15-year levels and independent of a 15-year change in levels. BACKGROUND: Few studies have used multiple measures over the course of time to predict subclinical atherosclerosis. METHODS: African American and white adults, ages 18 to 30 years, in 4 U.S. cities were enrolled in the prospective CARDIA (Coronary Artery Risk Development in Young Adults) study from 1985 to 1986. Risk factors were measured at years 0, 2, 5, 7, 10, and 15, and CAC was assessed at year 15 (n = 3,043). RESULTS: Overall, 9.6% adults had any CAC, with a greater prevalence among men than women (15.0% vs. 5.1%), white than African American men (17.6% vs. 11.3%), and ages 40 to 45 years than 33 to 39 years (13.3% vs. 5.5%). Baseline levels predicted CAC presence (C = 0.79) equally as well as average 15-year levels (C = 0.79; p = 0.8262) and better than concurrent levels (C = 0.77; p = 0.019), despite a 15-year change in risk factor levels. Multivariate-adjusted odds ratios of having CAC by ages 33 to 45 years were 1.5 (95% confidence interval [CI] 1.3 to 1.7) per 10 cigarettes, 1.5 (95% CI 1.3 to 1.8) per 30 mg/dl low-density lipoprotein cholesterol, 1.3 (95% CI 1.1 to 1.5) per 10 mm Hg systolic blood pressure, and 1.2 (95% CI 1.1 to 1.4) per 15 mg/dl glucose at baseline. Young adults with above optimal risk factor levels at baseline were 2 to 3 times as likely to have CAC. CONCLUSIONS: Early adult levels of modifiable risk factors, albeit low, were equally or more informative about odds of CAC in middle age than subsequent levels. Earlier risk assessment and efforts to achieve and maintain optimal risk factor levels may be needed.

Comparison of coronary heart disease risk factors in autopsied young adults from the PDAY Study with living young adults from the CARDIA study.

BACKGROUND: Disease is sometimes best studied by examination of tissue obtained from autopsied individuals. Results derived from autopsied persons are considered biased because many factors influence the decision to perform an autopsy, and variables measured postmortem may be affected by changes immediately prior to death and emergency medical treatment. METHODS: The Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study measured coronary heart disease risk factors postmortem in autopsied young adults 23-34 years of age dying from external causes (accidents, homicides, suicides). The Coronary Artery Risk Development in Young Adults (CARDIA) study measured risk factors in living subjects of similar ages. RESULTS: Within sex, race, and age groups, the differences in body mass index between PDAY and CARDIA were significant but small. The prevalences of hyperglycemia/diabetes within sex, race, and age groups were similar in PDAY and CARDIA; overall, blacks in PDAY, but not in CARDIA, had a higher prevalence than whites. Serum lipoprotein concentrations were slightly and significantly higher and significantly more variable in PDAY subjects than in CARDIA subjects; the greater variability was interpreted as due primarily to emergency medical treatment. Prevalences of smoking and hypertension were substantially higher in PDAY subjects. CONCLUSIONS: Although there were statistically significant differences, the overall similarity of the risk factors in the two studies supports the validity of investigating associations of risk factors measured postmortem with anatomically determined arterial lesions in autopsied young adults dying from external causes. The greater variability in postmortem serum measurements attenuates but does not obscure associations.

Prediction of coronary artery calcium in young adults using the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) risk score: the CARDIA study.

BACKGROUND: Using data from autopsied young people aged 15 to 34 years, the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study developed a risk score based on age, sex, smoking status, high-density lipoprotein and non-high-density lipoprotein cholesterol levels, and the presence of obesity, hyperglycemia, and hypertension to predict advanced coronary artery atherosclerosis. METHODS: The Coronary Artery Risk Development in Young Adults (CARDIA) study assessed coronary artery calcium (CAC) by computed tomography in young adults participating in the 15-year examination. The PDAY risk score was calculated from risk factors measured at the CARDIA examinations at years 0, 5, 10, and 15. RESULTS: Odds ratios for amount of CAC (6 ordinal categories) for a 1-point increase in risk score computed from the modifiable risk factors ranged from 1.10 to 1.16 (all statistically significant). Odds ratios for presence of any amount of CAC ranged from 1.09 to 1.15 (all statistically significant), with the highest odds ratio for the risk score at year 0. An increase in risk score between years 0 and 15 increased the odds of CAC, and a decrease in risk score decreased the odds of CAC. A positive family history of cardiovascular disease increased the odds of CAC. The c statistics ranged from 0.752 to 0.770, with the highest discrimination based on the year 0 revised PDAY risk score that included family history and increased the points for the sex differential. CONCLUSION: The PDAY risk score predicts CAC up to 15 years before its assessment, and risk score change during 15 years affects the risk of CAC.