@article {1499, title = {The Sleep Heart Health Study: design, rationale, and methods.}, journal = {Sleep}, volume = {20}, year = {1997}, month = {1997 Dec}, pages = {1077-85}, abstract = {

The Sleep Heart Health Study (SHHS) is a prospective cohort study designed to investigate obstructive sleep apnea (OSA) and other sleep-disordered breathing (SDB) as risk factors for the development of cardiovascular disease. The study is designed to enroll 6,600 adult participants aged 40 years and older who will undergo a home polysomnogram to assess the presence of OSA and other SDB. Participants in SHHS have been recruited from cohort studies in progress. Therefore, SHHS adds the assessment of OSA to the protocols of these studies and will use already collected data on the principal risk factors for cardiovascular disease as well as follow-up and outcome information pertaining to cardiovascular disease. Parent cohort studies and recruitment targets for these cohorts are the following: Atherosclerosis Risk in Communities Study (1,750 participants), Cardiovascular Health Study (1,350 participants), Framingham Heart Study (1,000 participants), Strong Heart Study (600 participants), New York Hypertension Cohorts (1,000 participants), and Tucson Epidemiologic Study of Airways Obstructive Diseases and the Health and Environment Study (900 participants). As part of the parent study follow-up procedures, participants will be surveyed at periodic intervals for the incidence and recurrence of cardiovascular disease events. The study provides sufficient statistical power for assessing OSA and other SDB as risk factors for major cardiovascular events, including myocardial infarction and stroke.

}, keywords = {Adult, Aged, Aged, 80 and over, Arteriosclerosis, Cohort Studies, Coronary Disease, Female, Humans, Hypertension, Longitudinal Studies, Male, Middle Aged, Polysomnography, Positive-Pressure Respiration, Prospective Studies, Research Design, Sleep Apnea Syndromes}, issn = {0161-8105}, author = {Quan, S F and Howard, B V and Iber, C and Kiley, J P and Nieto, F J and O{\textquoteright}Connor, G T and Rapoport, D M and Redline, S and Robbins, J and Samet, J M and Wahl, P W} } @article {633, title = {The association of sleep-disordered breathing and sleep symptoms with quality of life in the Sleep Heart Health Study.}, journal = {Sleep}, volume = {24}, year = {2001}, month = {2001 Feb 01}, pages = {96-105}, abstract = {

This study assessed the extent to which sleep-disordered breathing (SDB), difficulty initiating and maintaining sleep (DIMS), and excessive daytime sleepiness (EDS) were associated with impairment of quality of life (QoL) using the SF-36. Participants (n=5,816; mean age=63 years; 52.5\% women) were enrolled in the nation-wide population-based Sleep Heart Health Study (SHHS) implemented to investigate sleep-disordered breathing as a risk factor in the development of cardiovascular disease. Each transformed SF-36 scale was analyzed independently using multiple logistic regression analysis with sleep and other potential confounding variables (e.g., age, ethnicity) included as independent variables. Men (11.6\%) were significantly more likely to have SDB compared to women (5.6\%), while women (42.4\%) were significantly more likely to report DIMS than men (32.5\%). Vitality was the sole SF-36 scale to have a linear association with the clinical categories of SDB (mild, moderate, severe SDB). However, individuals with severe SDB indicated significantly poorer QoL on several SF-36 scales. Both DIMS and EDS were strongly associated with reduced QoL even after adjusting for confounding variables for both sexes. Findings suggest 1) mild to moderate SDB is associated with reduced vitality, while severe SDB is more broadly associated with poorer QoL, 2) subjective sleep symptoms are comprehensively associated with poorer QoL, and 3) SF-36 mean score profiles for SDB and sleep symptoms are equivalent to other chronic diseases in the U.S. general population.

}, keywords = {Adult, Cardiovascular Diseases, Chronic Disease, Circadian Rhythm, Disorders of Excessive Somnolence, Female, Health Status, Humans, Male, Middle Aged, Polysomnography, Population Surveillance, Prevalence, Quality of Life, Risk Factors, Severity of Illness Index, Sleep Apnea Syndromes, United States}, issn = {0161-8105}, doi = {10.1093/sleep/24.1.96}, author = {Baldwin, C M and Griffith, K A and Nieto, F J and O{\textquoteright}Connor, G T and Walsleben, J A and Redline, S} } @article {662, title = {Echocardiographic features of the right heart in sleep-disordered breathing: the Framingham Heart Study.}, journal = {Am J Respir Crit Care Med}, volume = {164}, year = {2001}, month = {2001 Sep 15}, pages = {933-8}, abstract = {

The effect of sleep-disordered breathing (SDB) on right heart structure and function is controversial. Studies of patients referred for evaluation of possible sleep apnea have yielded conflicting results, and the impact of SDB on the right heart has not been investigated in the general population. We examined the echocardiographic features of subjects with SDB at the Framingham Heart Study site of the Sleep Heart Health Study. Of 1,001 polysomnography subjects, 90 with SDB defined as a respiratory disturbance index (RDI) score > 90th percentile (mean RDI = 42) were compared with 90 low-RDI subjects (mean RDI = 5) matched for age, sex, and body mass index. Right heart measurements, made without knowledge of clinical status, were compared between groups. The majority of the subjects were male (74\%). After multivariable adjustment, right ventricle (RV) wall thickness was significantly greater (p = 0.005) in subjects with SDB (0.78 +/- 0.02 cm) than in the low-RDI subjects (0.68 +/- 0.02 cm). Right atrial dimensions, RV dimensions, and RV systolic function were not found to be significantly different between subjects with SDB and the low-RDI subjects. We conclude that in this community-based study of SDB and right heart echocardiographic features, RV wall thickness was increased in subjects with SDB. Whether the RV hypertrophy observed in persons with SDB is associated with increased morbidity and mortality remains unknown.

}, keywords = {Adult, Age Factors, Aged, Cohort Studies, Cross-Sectional Studies, Data Interpretation, Statistical, Echocardiography, Female, Forced Expiratory Volume, Humans, Hypertrophy, Right Ventricular, Linear Models, Male, Middle Aged, Obesity, Observer Variation, Polysomnography, Prospective Studies, Sex Factors, Sleep Apnea Syndromes, Ventricular Function, Right, Vital Capacity}, issn = {1073-449X}, doi = {10.1164/ajrccm.164.6.2001092}, author = {Guidry, U C and Mendes, L A and Evans, J C and Levy, D and O{\textquoteright}Connor, G T and Larson, M G and Gottlieb, D J and Benjamin, E J} } @article {636, title = {Sleep-disordered breathing and cardiovascular disease: cross-sectional results of the Sleep Heart Health Study.}, journal = {Am J Respir Crit Care Med}, volume = {163}, year = {2001}, month = {2001 Jan}, pages = {19-25}, abstract = {

Disordered breathing during sleep is associated with acute, unfavorable effects on cardiovascular physiology, but few studies have examined its postulated association with cardiovascular disease (CVD). We examined the cross-sectional association between sleep- disordered breathing and self-reported CVD in 6,424 free-living individuals who underwent overnight, unattended polysomnography at home. Sleep-disordered breathing was quantified by the apnea-hypopnea index (AHI)-the average number of apneas and hypopneas per hour of sleep. Mild to moderate disordered breathing during sleep was highly prevalent in the sample (median AHI: 4.4; interquartile range: 1.3 to 11.0). A total of 1,023 participants (16\%) reported at least one manifestation of CVD (myocardial infarction, angina, coronary revascularization procedure, heart failure, or stroke). The multivariable-adjusted relative odds (95\% CI) of prevalent CVD for the second, third, and fourth quartiles of the AHI (versus the first) were 0.98 (0.77-1.24), 1.28 (1.02-1.61), and 1.42 (1.13-1.78), respectively. Sleep-disordered breathing was associated more strongly with self-reported heart failure and stroke than with self-reported coronary heart disease: the relative odds (95\% CI) of heart failure, stroke, and coronary heart disease (upper versus lower AHI quartile) were 2.38 (1.22-4.62), 1.58 (1.02- 2.46), and 1.27 (0.99-1.62), respectively. These findings are compatible with modest to moderate effects of sleep-disordered breathing on heterogeneous manifestations of CVD within a range of AHI values that are considered normal or only mildly elevated.

}, keywords = {Aged, Cardiovascular Diseases, Cohort Studies, Cross-Sectional Studies, Female, Humans, Male, Middle Aged, Sleep Apnea Syndromes}, issn = {1073-449X}, doi = {10.1164/ajrccm.163.1.2001008}, author = {Shahar, E and Whitney, C W and Redline, S and Lee, E T and Newman, A B and Nieto, F J and O{\textquoteright}Connor, G T and Boland, L L and Schwartz, J E and Samet, J M} } @article {6081, title = {Adhesion molecules, endothelin-1 and lung function in seven population-based cohorts.}, journal = {Biomarkers}, volume = {18}, year = {2013}, month = {2013 May}, pages = {196-203}, abstract = {

CONTEXT: Endothelial function is abnormal in chronic obstructive pulmonary disease (COPD); whether endothelial dysfunction causes COPD is unknown.

OBJECTIVE: Test associations of endothelial biomarkers with FEV1 using instrumental variables.

METHODS: Among 26 907 participants with spirometry, ICAM-1, P-selectin, E-selectin and endothelin-1 were measured in subsets.

RESULTS: ICAM-1 and P-selectin were inversely associated with FEV1 among European-Americans (-29 mL and -34 mL per standard deviation of log-transformed biomarker, p < 0.001), as was endothelin-1 among African-Americans (-22 mL, p = 0.008). Genetically-estimated ICAM-1 and P-selectin were not significantly associated with FEV1. The instrumental variable for endothelin-1 was non-informative.

CONCLUSION: Although ICAM-1, P-selectin and endothelin-1 were inversely associated with FEV1, associations for ICAM-1 and P-selectin do not appear causal.

}, keywords = {African Continental Ancestry Group, Biomarkers, Cohort Studies, E-Selectin, Endothelin-1, Endothelium, Vascular, European Continental Ancestry Group, Female, Gene Expression, Humans, Intercellular Adhesion Molecule-1, Lung, Male, Middle Aged, P-Selectin, Pulmonary Disease, Chronic Obstructive, Respiratory Function Tests, Spirometry}, issn = {1366-5804}, doi = {10.3109/1354750X.2012.762805}, author = {Oelsner, E C and Pottinger, T D and Burkart, K M and Allison, M and Buxbaum, S G and Hansel, N N and Kumar, R and Larkin, E K and Lange, L A and Loehr, L R and London, S J and O{\textquoteright}Connor, G T and Papanicolaou, G and Petrini, M F and Rabinowitz, D and Raghavan, S and Redline, S and Thyagarajan, B and Tracy, R P and Wilk, J B and White, W B and Rich, S S and Barr, R G} } @article {6851, title = {Association of 25-Hydroxyvitamin D status and genetic variation in the vitamin D metabolic pathway with FEV1 in the Framingham Heart Study.}, journal = {Respir Res}, volume = {16}, year = {2015}, month = {2015}, pages = {81}, abstract = {

BACKGROUND: Vitamin D is associated with lung function in cross-sectional studies, and vitamin D inadequacy is hypothesized to play a role in the pathogenesis of chronic obstructive pulmonary disease. Further data are needed to clarify the relation between vitamin D status, genetic variation in vitamin D metabolic genes, and cross-sectional and longitudinal changes in lung function in healthy adults.

METHODS: We estimated the association between serum 25-hydroxyvitamin D [25(OH)D] and cross-sectional forced expiratory volume in the first second (FEV1) in Framingham Heart Study (FHS) Offspring and Third Generation participants and the association between serum 25(OH)D and longitudinal change in FEV1 in Third Generation participants using linear mixed-effects models. Using a gene-based approach, we investigated the association between 241 SNPs in 6 select vitamin D metabolic genes in relation to longitudinal change in FEV1 in Offspring participants and pursued replication of these findings in a meta-analyzed set of 4 independent cohorts.

RESULTS: We found a positive cross-sectional association between 25(OH)D and FEV1 in FHS Offspring and Third Generation participants (P=0.004). There was little or no association between 25(OH)D and longitudinal change in FEV1 in Third Generation participants (P=0.97). In Offspring participants, the CYP2R1 gene, hypothesized to influence usual serum 25(OH)D status, was associated with longitudinal change in FEV1 (gene-based P<0.05). The most significantly associated SNP from CYP2R1 had a consistent direction of association with FEV1 in the meta-analyzed set of replication cohorts, but the association did not reach statistical significance thresholds (P=0.09).

CONCLUSIONS: Serum 25(OH)D status was associated with cross-sectional FEV1, but not longitudinal change in FEV1. The inconsistent associations may be driven by differences in the groups studied. CYP2R1 demonstrated a gene-based association with longitudinal change in FEV1 and is a promising candidate gene for further studies.

}, keywords = {Adult, Aged, Cohort Studies, Cross-Sectional Studies, DNA-Binding Proteins, Female, Genetic Variation, Humans, Longitudinal Studies, Male, Massachusetts, Metabolic Networks and Pathways, Middle Aged, Nuclear Proteins, Polymorphism, Single Nucleotide, Vitamin D}, issn = {1465-993X}, doi = {10.1186/s12931-015-0238-y}, author = {Hansen, J G and Gao, W and Dupuis, J and O{\textquoteright}Connor, G T and Tang, W and Kowgier, M and Sood, A and Gharib, S A and Palmer, L J and Fornage, M and Heckbert, S R and Psaty, B M and Booth, S L and Cassano, Patricia A} } @article {6566, title = {Novel loci associated with usual sleep duration: the CHARGE Consortium Genome-Wide Association Study.}, journal = {Mol Psychiatry}, volume = {20}, year = {2015}, month = {2015 Oct}, pages = {1232-9}, abstract = {

Usual sleep duration is a heritable trait correlated with psychiatric morbidity, cardiometabolic disease and mortality, although little is known about the genetic variants influencing this trait. A genome-wide association study (GWAS) of usual sleep duration was conducted using 18 population-based cohorts totaling 47 180 individuals of European ancestry. Genome-wide significant association was identified at two loci. The strongest is located on chromosome 2, in an intergenic region 35- to 80-kb upstream from the thyroid-specific transcription factor PAX8 (lowest P=1.1 {\texttimes} 10(-9)). This finding was replicated in an African-American sample of 4771 individuals (lowest P=9.3 {\texttimes} 10(-4)). The strongest combined association was at rs1823125 (P=1.5 {\texttimes} 10(-10), minor allele frequency 0.26 in the discovery sample, 0.12 in the replication sample), with each copy of the minor allele associated with a sleep duration 3.1 min longer per night. The alleles associated with longer sleep duration were associated in previous GWAS with a more favorable metabolic profile and a lower risk of attention deficit hyperactivity disorder. Understanding the mechanisms underlying these associations may help elucidate biological mechanisms influencing sleep duration and its association with psychiatric, metabolic and cardiovascular disease.

}, keywords = {Adult, African Americans, Aged, Dyssomnias, European Continental Ancestry Group, Female, Genetic Association Studies, Genome-Wide Association Study, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Self Report, Sleep}, issn = {1476-5578}, doi = {10.1038/mp.2014.133}, author = {Gottlieb, D J and Hek, K and Chen, T-H and Watson, N F and Eiriksdottir, G and Byrne, E M and Cornelis, M and Warby, S C and Bandinelli, S and Cherkas, L and Evans, D S and Grabe, H J and Lahti, J and Li, M and Lehtim{\"a}ki, T and Lumley, T and Marciante, K D and P{\'e}russe, L and Psaty, B M and Robbins, J and Tranah, G J and Vink, J M and Wilk, J B and Stafford, J M and Bellis, C and Biffar, R and Bouchard, C and Cade, B and Curhan, G C and Eriksson, J G and Ewert, R and Ferrucci, L and F{\"u}l{\"o}p, T and Gehrman, P R and Goodloe, R and Harris, T B and Heath, A C and Hernandez, D and Hofman, A and Hottenga, J-J and Hunter, D J and Jensen, M K and Johnson, A D and K{\"a}h{\"o}nen, M and Kao, L and Kraft, P and Larkin, E K and Lauderdale, D S and Luik, A I and Medici, M and Montgomery, G W and Palotie, A and Patel, S R and Pistis, G and Porcu, E and Quaye, L and Raitakari, O and Redline, S and Rimm, E B and Rotter, J I and Smith, A V and Spector, T D and Teumer, A and Uitterlinden, A G and Vohl, M-C and Widen, E and Willemsen, G and Young, T and Zhang, X and Liu, Y and Blangero, J and Boomsma, D I and Gudnason, V and Hu, F and Mangino, M and Martin, N G and O{\textquoteright}Connor, G T and Stone, K L and Tanaka, T and Viikari, J and Gharib, S A and Punjabi, N M and R{\"a}ikk{\"o}nen, K and V{\"o}lzke, H and Mignot, E and Tiemeier, H} }