@article {1401, title = {Persistence and remission of musculoskeletal pain in community-dwelling older adults: results from the cardiovascular health study.}, journal = {J Am Geriatr Soc}, volume = {60}, year = {2012}, month = {2012 Aug}, pages = {1393-400}, abstract = {

OBJECTIVES: To characterize longitudinal patterns of musculoskeletal pain in a community sample of older adults over a 6-year period and to identify factors associated with persistence of pain.

DESIGN: Secondary analysis of the Cardiovascular Health Study.

SETTING: Community-based cohort drawn from four U.S. counties.

PARTICIPANTS: Five thousand ninety-three men and women aged 65 and older.

MEASUREMENTS: Over a 6-year period, pain was assessed each year using a single question about the presence of pain in any bones or joints during the last year. If affirmative, participants were queried about pain in seven locations (hands, shoulders, neck, back, hips, knees, feet). Participants were categorized according to the percentage of time that pain was present and according to the intermittent or chronic pattern of pain. Factors associated with persistent pain during five remaining years of the study were identified.

RESULTS: Over 6 years, 32\% of participants reported pain for three or more consecutive years, and 32\% reported pain intermittently. Of those who reported pain the first year, 54\% were pain free at least once during the follow-up period. Most of the pain at specific body locations was intermittent. Factors associated with remission of pain over 5 years included older age, male sex, better self-rated health, not being obese, taking fewer medications, and having fewer depressive symptoms. Approximately half of those with pain reported fewer pain locations the following year.

CONCLUSION: Musculoskeletal pain in older adults, despite high prevalence, is often intermittent. The findings refute the notion that pain is an inevitable, unremitting, or progressive consequence of aging.

}, keywords = {Aged, Aged, 80 and over, Cardiovascular Diseases, Female, Humans, Male, Musculoskeletal Pain, Remission Induction, Residence Characteristics}, issn = {1532-5415}, doi = {10.1111/j.1532-5415.2012.04082.x}, author = {Thielke, Stephen M and Whitson, Heather and Diehr, Paula and O{\textquoteright}Hare, Ann and Kearney, Patricia M and Chaudhry, Sarwat I and Zakai, Neil A and Kim, Dae and Sekaran, Nishant and Sale, Joanna E M and Arnold, Alice M and Chaves, Paulo and Newman, Anne} } @article {6588, title = {Risk factors for cardiovascular disease across the spectrum of older age: the Cardiovascular Health Study.}, journal = {Atherosclerosis}, volume = {237}, year = {2014}, month = {2014 Nov}, pages = {336-42}, abstract = {

OBJECTIVE: The associations of some risk factors with cardiovascular disease (CVD) are attenuated in older age; whereas others appear robust. The present study aimed to compare CVD risk factors across older age.

METHODS: Participants (n~=~4883) in the Cardiovascular Health Study free of prevalent CVD, were stratified into three age groups: 65-74, 75-84, 85+ years. Traditional risk factors included systolic blood pressure (BP), LDL-cholesterol, HDL-cholesterol, obesity, and diabetes. Novel risk factors included kidney function, C-reactive protein (CRP), and N-terminal pro-B-type natriuretic peptide (NT pro-BNP).

RESULTS: There were 1498 composite CVD events (stroke, myocardial infarction, and cardiovascular death) over 5 years. The associations of high systolic BP and diabetes appeared strongest, though both were attenuated with age (p-values for interaction~=~0.01 and 0.002, respectively). The demographic-adjusted hazard ratios (HR) for elevated systolic BP were 1.79 (95\% confidence interval: 1.49, 2.15), 1.59 (1.37, 1.85) and 1.10 (0.86, 1.41) in participants aged 65-74, 75-84, 85+, and for diabetes, 2.36 (1.89, 2.95), 1.55 (1.27, 1.89), 1.51 (1.10, 2.09). The novel risk factors had consistent associations with the outcome across the age spectrum; low kidney function: 1.69 (1.31, 2.19), 1.61 (1.36, 1.90), and 1.57 (1.16, 2.14) for 65-74, 75-84, and 85+ years, respectively; elevated CRP: 1.54 (1.28, 1.87), 1.33 (1.13, 1.55), and 1.51 (1.15, 1.97); elevated NT pro-BNP: 2.67 (1.96, 3.64), 2.71 (2.25, 3.27), and 2.18 (1.43, 3.45).

CONCLUSIONS: The associations of most traditional risk factors with CVD were minimal in the oldest old, whereas diabetes, eGFR, CRP, and NT pro-BNP were associated with CVD across older age.

}, keywords = {Aged, Aged, 80 and over, Blood Pressure, C-Reactive Protein, Cardiovascular Diseases, Cholesterol, HDL, Cholesterol, LDL, Diabetes Complications, Diabetes Mellitus, Female, Humans, Inflammation, Kidney, Kidney Diseases, Lipids, Male, Natriuretic Peptide, Brain, Obesity, Peptide Fragments, Risk Factors}, issn = {1879-1484}, doi = {10.1016/j.atherosclerosis.2014.09.012}, author = {Odden, Michelle C and Shlipak, Michael G and Whitson, Heather E and Katz, Ronit and Kearney, Patricia M and deFilippi, Chris and Shastri, Shani and Sarnak, Mark J and Siscovick, David S and Cushman, Mary and Psaty, Bruce M and Newman, Anne B} } @article {6682, title = {Genome of The Netherlands population-specific imputations identify an ABCA6 variant associated with cholesterol levels.}, journal = {Nat Commun}, volume = {6}, year = {2015}, month = {2015}, pages = {6065}, abstract = {

Variants associated with blood lipid levels may be population-specific. To identify low-frequency variants associated with this phenotype, population-specific reference panels may be used. Here we impute nine large Dutch biobanks (~35,000 samples) with the population-specific reference panel created by the Genome of The Netherlands Project and perform association testing with blood lipid levels. We report the discovery of five novel associations at four loci (P value <6.61 {\texttimes} 10(-4)), including a rare missense variant in ABCA6 (rs77542162, p.Cys1359Arg, frequency 0.034), which is predicted to be deleterious. The frequency of this ABCA6 variant is 3.65-fold increased in the Dutch and its effect (βLDL-C=0.135, βTC=0.140) is estimated to be very similar to those observed for single variants in well-known lipid genes, such as LDLR.

}, keywords = {ATP-Binding Cassette Transporters, Cholesterol, Gene Frequency, Genetic Association Studies, Humans, Mutation, Missense, Netherlands}, issn = {2041-1723}, doi = {10.1038/ncomms7065}, author = {van Leeuwen, Elisabeth M and Karssen, Lennart C and Deelen, Joris and Isaacs, Aaron and Medina-G{\'o}mez, Carolina and Mbarek, Hamdi and Kanterakis, Alexandros and Trompet, Stella and Postmus, Iris and Verweij, Niek and van Enckevort, David J and Huffman, Jennifer E and White, Charles C and Feitosa, Mary F and Bartz, Traci M and Manichaikul, Ani and Joshi, Peter K and Peloso, Gina M and Deelen, Patrick and van Dijk, Freerk and Willemsen, Gonneke and de Geus, Eco J and Milaneschi, Yuri and Penninx, Brenda W J H and Francioli, Laurent C and Menelaou, Androniki and Pulit, Sara L and Rivadeneira, Fernando and Hofman, Albert and Oostra, Ben A and Franco, Oscar H and Mateo Leach, Irene and Beekman, Marian and de Craen, Anton J M and Uh, Hae-Won and Trochet, Holly and Hocking, Lynne J and Porteous, David J and Sattar, Naveed and Packard, Chris J and Buckley, Brendan M and Brody, Jennifer A and Bis, Joshua C and Rotter, Jerome I and Mychaleckyj, Josyf C and Campbell, Harry and Duan, Qing and Lange, Leslie A and Wilson, James F and Hayward, Caroline and Polasek, Ozren and Vitart, Veronique and Rudan, Igor and Wright, Alan F and Rich, Stephen S and Psaty, Bruce M and Borecki, Ingrid B and Kearney, Patricia M and Stott, David J and Adrienne Cupples, L and Jukema, J Wouter and van der Harst, Pim and Sijbrands, Eric J and Hottenga, Jouke-Jan and Uitterlinden, Andr{\'e} G and Swertz, Morris A and van Ommen, Gert-Jan B and de Bakker, Paul I W and Eline Slagboom, P and Boomsma, Dorret I and Wijmenga, Cisca and van Duijn, Cornelia M} } @article {6795, title = {Subclinical thyroid dysfunction and fracture risk: a meta-analysis.}, journal = {JAMA}, volume = {313}, year = {2015}, month = {2015 May 26}, pages = {2055-65}, abstract = {

IMPORTANCE: Associations between subclinical thyroid dysfunction and fractures are unclear and clinical trials are lacking.

OBJECTIVE: To assess the association of subclinical thyroid dysfunction with hip, nonspine, spine, or any fractures.

DATA SOURCES AND STUDY SELECTION: The databases of MEDLINE and EMBASE (inception to March 26, 2015) were searched without language restrictions for prospective cohort studies with thyroid function data and subsequent fractures.

DATA EXTRACTION: Individual participant data were obtained from 13 prospective cohorts in the United States, Europe, Australia, and Japan. Levels of thyroid function were defined as euthyroidism (thyroid-stimulating hormone [TSH], 0.45-4.49 mIU/L), subclinical hyperthyroidism (TSH <0.45 mIU/L), and subclinical hypothyroidism (TSH >=4.50-19.99 mIU/L) with normal thyroxine concentrations.

MAIN OUTCOME AND MEASURES: The primary outcome was hip fracture. Any fractures, nonspine fractures, and clinical spine fractures were secondary outcomes.

RESULTS: Among 70,298 participants, 4092 (5.8\%) had subclinical hypothyroidism and 2219 (3.2\%) had subclinical hyperthyroidism. During 762,401 person-years of follow-up, hip fracture occurred in 2975 participants (4.6\%; 12 studies), any fracture in 2528 participants (9.0\%; 8 studies), nonspine fracture in 2018 participants (8.4\%; 8 studies), and spine fracture in 296 participants (1.3\%; 6 studies). In age- and sex-adjusted analyses, the hazard ratio (HR) for subclinical hyperthyroidism vs euthyroidism was 1.36 for hip fracture (95\% CI, 1.13-1.64; 146 events in 2082 participants vs 2534 in 56,471); for any fracture, HR was 1.28 (95\% CI, 1.06-1.53; 121 events in 888 participants vs 2203 in 25,901); for nonspine fracture, HR was 1.16 (95\% CI, 0.95-1.41; 107 events in 946 participants vs 1745 in 21,722); and for spine fracture, HR was 1.51 (95\% CI, 0.93-2.45; 17 events in 732 participants vs 255 in 20,328). Lower TSH was associated with higher fracture rates: for TSH of less than 0.10 mIU/L, HR was 1.61 for hip fracture (95\% CI, 1.21-2.15; 47 events in 510 participants); for any fracture, HR was 1.98 (95\% CI, 1.41-2.78; 44 events in 212 participants); for nonspine fracture, HR was 1.61 (95\% CI, 0.96-2.71; 32 events in 185 participants); and for spine fracture, HR was 3.57 (95\% CI, 1.88-6.78; 8 events in 162 participants). Risks were similar after adjustment for other fracture risk factors. Endogenous subclinical hyperthyroidism (excluding thyroid medication users) was associated with HRs of 1.52 (95\% CI, 1.19-1.93) for hip fracture, 1.42 (95\% CI, 1.16-1.74) for any fracture, and 1.74 (95\% CI, 1.01-2.99) for spine fracture. No association was found between subclinical hypothyroidism and fracture risk.

CONCLUSIONS AND RELEVANCE: Subclinical hyperthyroidism was associated with an increased risk of hip and other fractures, particularly among those with TSH levels of less than 0.10 mIU/L and those with endogenous subclinical hyperthyroidism. Further study is needed to determine whether treating subclinical hyperthyroidism can prevent fractures.

}, keywords = {Adolescent, Adult, Aged, Aged, 80 and over, Female, Fractures, Bone, Hip Fractures, Humans, Hyperthyroidism, Hypothyroidism, Male, Middle Aged, Risk Factors, Spinal Fractures, Thyrotropin, Young Adult}, issn = {1538-3598}, doi = {10.1001/jama.2015.5161}, author = {Blum, Manuel R and Bauer, Douglas C and Collet, Tinh-Hai and Fink, Howard A and Cappola, Anne R and da Costa, Bruno R and Wirth, Christina D and Peeters, Robin P and Asvold, Bj{\o}rn O and den Elzen, Wendy P J and Luben, Robert N and Imaizumi, Misa and Bremner, Alexandra P and Gogakos, Apostolos and Eastell, Richard and Kearney, Patricia M and Strotmeyer, Elsa S and Wallace, Erin R and Hoff, Mari and Ceresini, Graziano and Rivadeneira, Fernando and Uitterlinden, Andr{\'e} G and Stott, David J and Westendorp, Rudi G J and Khaw, Kay-Tee and Langhammer, Arnuf and Ferrucci, Luigi and Gussekloo, Jacobijn and Williams, Graham R and Walsh, John P and J{\"u}ni, Peter and Aujesky, Drahomir and Rodondi, Nicolas} } @article {6798, title = {Thyroid function within the normal range and risk of coronary heart disease: an individual participant data analysis of 14 cohorts.}, journal = {JAMA Intern Med}, volume = {175}, year = {2015}, month = {2015 Jun}, pages = {1037-47}, abstract = {

IMPORTANCE: Some experts suggest that serum thyrotropin levels in the upper part of the current reference range should be considered abnormal, an approach that would reclassify many individuals as having mild hypothyroidism. Health hazards associated with such thyrotropin levels are poorly documented, but conflicting evidence suggests that thyrotropin levels in the upper part of the reference range may be associated with an increased risk of coronary heart disease (CHD).

OBJECTIVE: To assess the association between differences in thyroid function within the reference range and CHD risk.

DESIGN, SETTING, AND PARTICIPANTS: Individual participant data analysis of 14 cohorts with baseline examinations between July 1972 and April 2002 and with median follow-up ranging from 3.3 to 20.0 years. Participants included 55,412 individuals with serum thyrotropin levels of 0.45 to 4.49 mIU/L and no previously known thyroid or cardiovascular disease at baseline.

EXPOSURES: Thyroid function as expressed by serum thyrotropin levels at baseline.

MAIN OUTCOMES AND MEASURES: Hazard ratios (HRs) of CHD mortality and CHD events according to thyrotropin levels after adjustment for age, sex, and smoking status.

RESULTS: Among 55,412 individuals, 1813 people (3.3\%) died of CHD during 643,183 person-years of follow-up. In 10 cohorts with information on both nonfatal and fatal CHD events, 4666 of 48,875 individuals (9.5\%) experienced a first-time CHD event during 533,408 person-years of follow-up. For each 1-mIU/L higher thyrotropin level, the HR was 0.97 (95\% CI, 0.90-1.04) for CHD mortality and 1.00 (95\% CI, 0.97-1.03) for a first-time CHD event. Similarly, in analyses by categories of thyrotropin, the HRs of CHD mortality (0.94 [95\% CI, 0.74-1.20]) and CHD events (0.97 [95\% CI, 0.83-1.13]) were similar among participants with the highest (3.50-4.49 mIU/L) compared with the lowest (0.45-1.49 mIU/L) thyrotropin levels. Subgroup analyses by sex and age group yielded similar results.

CONCLUSIONS AND RELEVANCE: Thyrotropin levels within the reference range are not associated with risk of CHD events or CHD mortality. This finding suggests that differences in thyroid function within the population reference range do not influence the risk of CHD. Increased CHD risk does not appear to be a reason for lowering the upper thyrotropin reference limit.

}, keywords = {Cohort Studies, Coronary Disease, Humans, Hypothyroidism, Thyrotropin}, issn = {2168-6114}, doi = {10.1001/jamainternmed.2015.0930}, author = {Asvold, Bj{\o}rn O and Vatten, Lars J and Bj{\o}ro, Trine and Bauer, Douglas C and Bremner, Alexandra and Cappola, Anne R and Ceresini, Graziano and den Elzen, Wendy P J and Ferrucci, Luigi and Franco, Oscar H and Franklyn, Jayne A and Gussekloo, Jacobijn and Iervasi, Giorgio and Imaizumi, Misa and Kearney, Patricia M and Khaw, Kay-Tee and Maciel, Rui M B and Newman, Anne B and Peeters, Robin P and Psaty, Bruce M and Razvi, Salman and Sgarbi, Jos{\'e} A and Stott, David J and Trompet, Stella and Vanderpump, Mark P J and V{\"o}lzke, Henry and Walsh, John P and Westendorp, Rudi G J and Rodondi, Nicolas} }