We integrate the theory of gender role congruity with extant research on servant leadership to propose and test a moderated process model in which we hypothesize that servant leadership's effects on ...outcomes are stronger when implemented by women, and when it takes place within teams high in feminine gender role composition. Specifically, we theorize that servant leadership's communal emphases on stakeholders and relationships align with female role prototypes, which should lead to female advantages for job performance through the proposed serial mediators of prosocial motivation and follower servant leadership behaviors. We test this moderated, serial‐mediation model in a temporally lagged field study with a multi‐organizational sample including 109 teams. We find evidence that the mediated process model is moderated at the first stage such that in teams higher in feminine gender role composition, servant leadership has greater direct effects on prosocial motivation, as well as indirect effects on follower servant leadership and performance. We do not find support for our hypothesis that a similar moderated effect would emerge for leader sex; instead, we find that the effect of servant leadership on follower servant leadership, and subsequently to performance, is stronger for women leaders than it is for men. The implications of these findings for the servant leadership and role congruity literatures are discussed.
A new class of highly potent NS5A inhibitors with an unsymmetric benzimidazole-difluorofluorene-imidazole core and distal 2.2.1azabicyclic ring system was discovered. Optimization of antiviral ...potency and pharmacokinetics led to the identification of 39 (ledipasvir, GS-5885). Compound 39 (GT1a replicon EC50 = 31 pM) has an extended plasma half-life of 37–45 h in healthy volunteers and produces a rapid >3 log viral load reduction in monotherapy at oral doses of 3 mg or greater with once-daily dosing in genotype 1a HCV-infected patients. 39 has been shown to be safe and efficacious, with SVR12 rates up to 100% when used in combination with direct-acting antivirals having complementary mechanisms.
BACKGROUND:Mechanisms underlying the association between age-related arterial stiffening and poor brain health remain elusive. Cerebral blood flow (CBF) homeostasis may be implicated. This study ...evaluates how aortic stiffening relates to resting CBF and cerebrovascular reactivity (CVR) in older adults.
METHODS:Vanderbilt Memory & Aging Project participants free of clinical dementia, stroke, and heart failure were studied, including older adults with normal cognition (n=155; age, 72±7 years; 59% male) or mild cognitive impairment (n=115; age, 73±7 years; 57% male). Aortic pulse wave velocity (PWV; meters per second) was quantified from cardiac magnetic resonance. Resting CBF (milliliters per 100 g per minute) and CVR (CBF response to hypercapnic normoxia stimulus) were quantified from pseudocontinuous arterial spin labeling magnetic resonance imaging. Linear regression models related aortic PWV to regional CBF, adjusting for age, race/ethnicity, education, Framingham Stroke Risk Profile (diabetes mellitus, smoking, left ventricular hypertrophy, prevalent cardiovascular disease, atrial fibrillation), hypertension, body mass index, apolipoprotein E4 (APOE ε4) status, and regional tissue volume. Models were repeated testing PWV×APOE ε4 interactions. Sensitivity analyses excluded participants with prevalent cardiovascular disease and atrial fibrillation.
RESULTS:Among participants with normal cognition, higher aortic PWV related to lower frontal lobe CBF (β=−0.43; P=0.04) and higher CVR in the whole brain (β=0.11; P=0.02), frontal lobes (β=0.12; P<0.05), temporal lobes (β=0.11; P=0.02), and occipital lobes (β=0.14; P=0.01). Among APOE ε4 carriers with normal cognition, findings were more pronounced with higher PWV relating to lower whole-brain CBF (β=−1.16; P=0.047), lower temporal lobe CBF (β=−1.81; P=0.004), and higher temporal lobe CVR (β=0.26; P=0.08), although the last result did not meet the a priori significance threshold. Results were similar in sensitivity models. Among participants with mild cognitive impairment, higher aortic PWV related to lower CBF in the occipital lobe (β=−0.70; P=0.02), but this finding was attenuated when participants with prevalent cardiovascular disease and atrial fibrillation were excluded. Among APOE ε4 carriers with mild cognitive impairment, findings were more pronounced with higher PWV relating to lower temporal lobe CBF (β=−1.20; P=0.02).
CONCLUSIONS:Greater aortic stiffening relates to lower regional CBF and higher CVR in cognitively normal older adults, especially among individuals with increased genetic predisposition for Alzheimer’s disease. Central arterial stiffening may contribute to reductions in regional CBF despite preserved cerebrovascular reserve capacity.
Smokers have lower risk of obesity, which some consider a "beneficial" side effect of smoking. However, some studies suggest that smoking is simultaneously associated with higher central adiposity ...and, more specifically, ectopic adipose deposition. Little is known about the association of smoking with intermuscular adipose tissue (IMAT), an ectopic adipose depot associated with cardiovascular disease (CVD) risk and a key determinant of muscle quality and function. We tested the hypothesis that smokers have higher abdominal IMAT and lower lean muscle quality than never smokers. We measured abdominal muscle total, lean, and adipose volumes (in cubic centimeters) and attenuation (in Hounsfield units HU) along with subcutaneous (SAT) and visceral adipose tissue (VAT) volumes using computed tomography (CT) in 3,020 middle-aged Coronary Artery Risk Development in Young Adults (CARDIA) participants (age 42-58, 56.3% women, 52.6% white race) at the year 25 (Y25) visit. The longitudinal CARDIA study was initiated in 1985 with the recruitment of young adult participants (aged 18-30 years) equally balanced by female and male sex and black and white race at 4 field centers located in Birmingham, AL, Chicago, IL, Minneapolis, MN, and Oakland, CA. Multivariable linear models included potential confounders such as physical activity and dietary habits along with traditional CVD risk factors. Current smokers had lower BMI than never smokers. Nevertheless, in the fully adjusted multivariable model with potential confounders, including BMI and CVD risk factors, adjusted mean (95% CI) IMAT volume was 2.66 (2.55-2.76) cm.sup.3 in current smokers (n = 524), 2.36 (2.29-2.43) cm.sup.3 in former smokers (n = 944), and 2.23 (2.18-2.29) cm.sup.3 in never smokers (n = 1,552) (p = 0.007 for comparison of former versus never smoker, and p < 0.001 for comparison of current smoker versus never and former smoker). Moreover, compared to participants who never smoked throughout life (41.6 41.3-41.9 HU), current smokers (40.4 39.9-40.9 HU) and former smokers (40.8 40.5-41.2 HU) had lower lean muscle attenuation suggesting lower muscle quality in the fully adjusted model (p < 0.001 for comparison of never smokers with either of the other two strata). Among participants who had ever smoked, pack-years of smoking exposure were directly associated with IMAT volume (beta 95% CI: 0.017 0.010-0.025) (p < 0.001). Despite having less SAT, current smokers also had higher VAT/SAT ratio than never smokers. These findings must be viewed with caution as residual confounding and/or reverse causation may contribute to these associations. We found that, compared to those who never smoked, current and former smokers had abdominal muscle composition that was higher in adipose tissue volume, a finding consistent with higher CVD risk and age-related physical deconditioning. These findings challenge the belief that smoking-associated weight loss or maintenance confers a health benefit.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
IMPORTANCE Younger individuals are experiencing a greater cumulative exposure to excess adiposity over their lifetime. However, few studies have determined the consequences of long-term obesity. ...OBJECTIVE To examine whether the duration of overall and abdominal obesity was associated with the presence and 10-year progression of coronary artery calcification (CAC), a subclinical predictor of coronary heart disease. DESIGN, SETTING, AND PARTICIPANTS Prospective study of 3275 white and black adults aged 18 to 30 years at baseline in 1985-1986 who did not initially have overall obesity (body mass index BMI ≥30) or abdominal obesity (men: waist circumference WC >102 cm; women: >88 cm) in the multicenter, community-based Coronary Artery Risk Development in Young Adults (CARDIA) study. Participants completed computed tomography scanning for the presence of CAC during the 15-, 20-, or 25-year follow-up examinations. Duration of overall and abdominal obesity was calculated using repeat measurements of BMI and WC, respectively, performed 2, 5, 7, 10, 15, 20, and 25 years after baseline. MAIN OUTCOMES AND MEASURES Presence of CAC was measured by computed tomography at the year 15 (2000-2001), year 20 (2005-2006), or year 25 (2010-2011) follow-up examinations. Ten-year progression of CAC (2000-2001 to 2010-2011) was defined as incident CAC in 2010-2011 or an increase in CAC score of 20 Agatston units or greater. RESULTS During follow-up, 40.4% and 41.0% developed overall and abdominal obesity, respectively. Rates of CAC per 1000 person-years were higher for those who experienced more than 20 years vs 0 years of overall obesity (16.0 vs 11.0, respectively) and abdominal obesity (16.7 vs 11.0). Approximately 25.2% and 27.7% of those with more than 20 years of overall and abdominal obesity, respectively, experienced progression of CAC vs 20.2% and 19.5% of those with 0 years. After adjustment for BMI or WC and potential confounders, the hazard ratios for CAC for each additional year of overall or abdominal obesity were 1.02 (95% CI, 1.01-1.03) and 1.03 (95% CI, 1.02-1.05), respectively. The adjusted odds ratios for CAC progression were 1.04 (95% CI, 1.01-1.06) and 1.04 (95% CI, 1.01-1.07), respectively. Associations were attenuated but largely persisted following additional adjustment for potential intermediate metabolic factors during follow-up. CONCLUSIONS AND RELEVANCE Longer duration of overall and abdominal obesity was associated with subclinical coronary heart disease and its progression through midlife independent of the degree of adiposity. Preventing or at least delaying the onset of obesity in young adulthood may lower the risk of developing atherosclerosis through middle age.
To examine whether premenopausal reproductive age, as indicated by serum antimüllerian hormone (AMH), is associated with leukocyte aging biomarkers.
Prospective cohort analysis.
The Coronary Artery ...Risk Development in Young Adults study, a population-based study of Black and White adults from four US communities (Birmingham, AL; Chicago, IL; Minneapolis, MN; Oakland, CA).
Premenopausal women with serum AMH measures at examination year 15 as well as leukocyte aging markers.
None.
Telomere length, mitochondrial deoxyribonucleic acid (mtDNA) copy number, and intrinsic and extrinsic epigenetic age acceleration (EAA) at examination years 15, 20, and 25 as well as change between examination years.
Women were 40.2 (standard deviation, 3.7) years of age at examination year 15 when the AMH and initial measures of telomere length and mtDNA copy number (n = 386) were obtained and EAA occurred. After adjustment for chronological age, race, and smoking history, AMH quartile at examination year 15 was not associated with telomere length at examination years 15 and 25 or telomere length change between these years, mtDNA copy number at examination years 15 and 25 or change between these years, or intrinsic EAA at examination years 15 and 20 or change between these years. Women in the second AMH quartile had faster extrinsic EAA than women in the lowest AMH quartile (β-coefficient, 1.84; 95% confidence interval, 0.20–3.49).
In a population-based cohort, AMH did not have associations with leukocyte telomere length, mtDNA copy number, or intrinsic EAA.
Hormona antimülleriana y marcadores de envejecimiento leucocitario en el estudio del desarrollo de riesgo de las arterias coronarias en adultos jóvenes.
Examinar si la edad reproductiva premenopáusica, según lo indicado por la hormona antimülleriana sérica (AMH), está asociada con biomarcadores de envejecimiento en leucocitos.
Análisis de cohorte prospectivo.
El estudio de desarrollo de riesgo de las arterias coronarias en adultos jóvenes es un estudio poblacional de adultos blancos y negros de cuatro comunidades estadounidenses (Birmingham, AL; Chicago, IL; Minneapolis, MN; Oakland, CA).
Mujeres premenopáusicas con medidas séricas de AMH en el año 15 de examen, así como marcadores de envejecimiento de leucocitos.
Ninguna.
longitud de los telómeros, número de copias del ácido desoxirribonucleico mitocondrial (ADNmt), y resistencia intrínseca y extrínseca de aceleración de la edad epigenética (EAA) en los años de examen 15, 20 y 25, así como el cambio entre los años de examen.
Las mujeres tenían 40,2 (desviación estándar, 3,7) años de edad en el año 15 del examen cuando se obtuvieron la AMH y las medidas iniciales de la longitud de los telómeros y el número de copias de mtDNA (n = 386) y se produjo la EAA. Después de ajustar por edad cronológica, raza y antecedentes de tabaquismo, el cuartil de AMH en el año de examen 15 no se asoció con la longitud de los telómeros en los años de examen 15 y 25 o cambio en la longitud de los telómeros entre estos años, número de copias de mtDNA en los años de examen 15 y 25 o cambio entre estos años, o EAA intrínseco en los años de examen 15 y 20 o cambio entre estos años. Las mujeres en el segundo cuartil de AMH tenían más rápidas EAA extrínsecas que las mujeres en el cuartil más bajo de AMH (coeficiente b, 1,84; intervalo de confianza del 95%, 0,20–3,49).
En una cohorte basada en la población, la AMH no tuvo asociaciones con la longitud de los telómeros de los leucocitos, el número de copias de mtDNA o EAA intrínseco.
Coronary artery calcium (CAC) is associated with coronary heart disease (CHD) and cardiovascular disease (CVD); however, prognostic data on CAC are limited in younger adults.
To determine if CAC in ...adults aged 32 to 46 years is associated with incident clinical CHD, CVD, and all-cause mortality during 12.5 years of follow-up.
The Coronary Artery Risk Development in Young Adults (CARDIA) Study is a prospective community-based study that recruited 5115 black and white participants aged 18 to 30 years from March 25, 1985, to June 7, 1986. The cohort has been under surveillance for 30 years, with CAC measured 15 (n = 3043), 20 (n = 3141), and 25 (n = 3189) years after recruitment. The mean follow-up period for incident events was 12.5 years, from the year 15 computed tomographic scan through August 31, 2014.
Incident CHD included fatal or nonfatal myocardial infarction, acute coronary syndrome without myocardial infarction, coronary revascularization, or CHD death. Incident CVD included CHD, stroke, heart failure, and peripheral arterial disease. Death included all causes. The probability of developing CAC by age 32 to 56 years was estimated using clinical risk factors measured 7 years apart between ages 18 and 38 years.
At year 15 of the study among 3043 participants (mean SD age, 40.3 3.6 years; 1383 men and 1660 women), 309 individuals (10.2%) had CAC, with a geometric mean Agatston score of 21.6 (interquartile range, 17.3-26.8). Participants were followed up for 12.5 years, with 57 incident CHD events and 108 incident CVD events observed. After adjusting for demographics, risk factors, and treatments, those with any CAC experienced a 5-fold increase in CHD events (hazard ratio HR, 5.0; 95% CI, 2.8-8.7) and 3-fold increase in CVD events (HR, 3.0; 95% CI, 1.9-4.7). Within CAC score strata of 1-19, 20-99, and 100 or more, the HRs for CHD were 2.6 (95% CI, 1.0-5.7), 5.8 (95% CI, 2.6-12.1), and 9.8 (95% CI, 4.5-20.5), respectively. A CAC score of 100 or more had an incidence of 22.4 deaths per 100 participants (HR, 3.7; 95% CI, 1.5-10.0); of the 13 deaths in participants with a CAC score of 100 or more, 10 were adjudicated as CHD events. Risk factors for CVD in early adult life identified those above the median risk for developing CAC and, if applied, in a selective CAC screening strategy could reduce the number of people screened for CAC by 50% and the number imaged needed to find 1 person with CAC from 3.5 to 2.2.
The presence of CAC among individuals aged between 32 and 46 years was associated with increased risk of fatal and nonfatal CHD during 12.5 years of follow-up. A CAC score of 100 or more was associated with early death. Adults younger than 50 years with any CAC, even with very low scores, identified on a computed tomographic scan are at elevated risk of clinical CHD, CVD, and death. Selective use of screening for CAC might be considered in individuals with risk factors in early adulthood to inform discussions about primary prevention.
Abstract Objective Non-alcoholic fatty liver disease (NAFLD) is an obesity-related condition associated with cardiovascular mortality. Yet, whether or not NAFLD is independently related to ...atherosclerosis is unclear. In a population-based cross-sectional sample of middle-aged adults free from liver or heart disease, we tested the hypothesis that NAFLD is associated with subclinical atherosclerosis (coronary artery (CAC) and abdominal aortic calcification (AAC)) independent of obesity. Methods Participants from the Coronary Artery Risk Development in Young Adults study with CT quantification of liver fat, CAC and AAC were included ( n = 2424). NAFLD was defined as liver attenuation ≤40 Hounsfield Units after exclusion of other causes of liver fat. CAC and AAC presence was defined as Agatston score >0. Results Mean participant age was 50.1 ± 3.6 years, (42.7% men, 50.0% black) and BMI was 30.6 ± 7.2 kg/m2 . The prevalence of NAFLD, CAC, and AAC was 9.6%, 27.1%, and 51.4%. NAFLD participants had increased prevalence of CAC (37.9% vs. 26.0%, p < 0.001) and AAC (65.1% vs. 49.9%, p < 0.001). NAFLD remained associated with CAC (OR, 1.33; 95% CI, 1.001–1.82) and AAC (OR, 1.74; 95% CI, 1.29–2.35) after adjustment for demographics and health behaviors. However, these associations were attenuated after additional adjustment for visceral adipose tissue (CAC OR, 1.05; 95% CI, 0.74–1.48, AAC OR = 1.20; 95% CI, 0.86–1.67). There was no interaction by race or sex. Conclusion In contrast to prior research, these findings suggest that obesity attenuates the relationship between NAFLD and subclinical atherosclerosis. Further studies evaluating the role of NAFLD duration on atherosclerotic progression and cardiovascular events are needed.
The prevalence of nonalcoholic fatty liver disease is rapidly rising. We aimed to investigate associations of diet quality and dietary patterns with nonalcoholic fatty liver disease (NAFLD) in Black ...and White adults. We included 1726 participants who attended the Year 20 Exam of the Coronary Artery Risk Development in Young Adults (CARDIA) study and had their liver attenuation (LA) measured using computed tomography at Year 25 (2010-2011). NAFLD was defined as an LA of ≤51 Hounsfield units after the exclusion of other causes of liver fat. The a priori diet-quality score (APDQS) was used to assess diet quality, and dietary patterns were derived from principal components analysis. Univariate and multivariable logistic regression models were used to evaluate the association between the APDQS, dietary patterns, and NAFLD, and were adjusted for Year 20 covariates. NAFLD prevalence at Year 25 was 23.6%. In a model adjusted for age, race, sex, education, alcohol use, physical activity, smoking, and center at Year 25, the APDQS was inversely associated (
= 0.004) and meat dietary pattern was positively associated (
< 0.0001) with NAFLD, while the fruit-vegetable dietary pattern was not significantly associated (
= 0.40). These associations remained significant when additionally adjusting for comorbidities (type 2 diabetes mellitus, dyslipidemia, hypertension), however, significant associations were diminished after additionally adjusting for body mass index (BMI). Overall, this study finds that the APDQS and meat dietary patterns are associated with prevalent NAFLD in mid-life. The associations appear to be partially mediated through higher BMI.
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