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1.  Adult height and the risk of cause-specific death and vascular morbidity in 1 million people: individual participant meta-analysis 
Wormser, David | Angelantonio, Emanuele Di | Kaptoge, Stephen | Wood, Angela M | Gao, Pei | Sun, Qi | Walldius, Göran | Selmer, Randi | Verschuren, WM Monique | Bueno-de-Mesquita, H Bas | Engström, Gunnar | Ridker, Paul M | Njølstad, Inger | Iso, Hiroyasu | Holme, Ingar | Giampaoli, Simona | Tunstall-Pedoe, Hugh | Gaziano, J Michael | Brunner, Eric | Kee, Frank | Tosetto, Alberto | Meisinger, Christa | Brenner, Hermann | Ducimetiere, Pierre | Whincup, Peter H | Tipping, Robert W | Ford, Ian | Cremer, Peter | Hofman, Albert | Wilhelmsen, Lars | Clarke, Robert | de Boer, Ian H | Jukema, J Wouter | Ibañez, Alejandro Marín | Lawlor, Debbie A | D'Agostino, Ralph B | Rodriguez, Beatriz | Casiglia, Edoardo | Stehouwer, Coen DA | Simons, Leon A | Nietert, Paul J | Barrett-Connor, Elizabeth | Panagiotakos, Demosthenes B | Björkelund, Cecilia | Strandberg, Timo E | Wassertheil-Smoller, Sylvia | Blazer, Dan G | Meade, Tom W | Welin, Lennart | Svärdsudd, Kurt | Woodward, Mark | Nissinen, Aulikki | Kromhout, Daan | Jørgensen, Torben | Tilvis, Reijo S | Guralnik, Jack M | Rosengren, Annika | Taylor, James O | Kiechl, Stefan | Dagenais, Gilles R | Gerry, F | Fowkes, R | Wallace, Robert B | Khaw, Kay-Tee | Shaffer, Jonathan A | Visser, Marjolein | Kauhanen, Jussi | Salonen, Jukka T | Gallacher, John | Ben-Shlomo, Yoav | Kitamura, Akihiko | Sundström, Johan | Wennberg, Patrik | Kiyohara, Yutaka | Daimon, Makoto | de la Cámara, Agustin Gómez | Cooper, Jackie A | Onat, Altan | Devereux, Richard | Mukamal, Kenneth J | Dankner, Rachel | Knuiman, Matthew W | Crespo, Carlos J | Gansevoort, Ron T | Goldbourt, Uri | Nordestgaard, Børge G | Shaw, Jonathan E | Mussolino, Michael | Nakagawa, Hidaeki | Fletcher, Astrid | Kuller, Lewis H | Gillum, Richard F | Gudnason, Vilmundur | Assmann, Gerd | Wald, Nicholas | Jousilahti, Pekka R | Greenland, Philip | Trevisan, Maurizio | Ulmer, Hanno | Butterworth, Adam S | Folsom, Aaron R | Davey-Smith, George | Hu, Frank B | Danesh, John | Tipping, Robert W | Ford, Charles E | Simpson, Lara M | Walldius, Göran | Jungner, Ingmar | Folsom, Aaron R | Demerath, Ellen W | Franceschini, Nora | Lutsey, Pamela L | Panagiotakos, Demosthenes B | Pitsavos, Christos | Chrysohoou, Christina | Stefanadis, Christodoulos | Shaw, Jonathan E | Atkins, Robert | Zimmet, Paul Z | Barr, Elizabeth LM | Knuiman, Matthew W | Whincup, Peter H | Wannamethee, S Goya | Morris, Richard W | Willeit, Johann | Kiechl, Stefan | Weger, Siegfried | Oberhollenzer, Friedrich | Wald, Nicholas | Ebrahim, Shah | Lawlor, Debbie A | Gallacher, John | Ben-Shlomo, Yoav | Yarnell, John WG | Casiglia, Edoardo | Tikhonoff, Valérie | Greenland, Philip | Shay, Christina M | Garside, Daniel B | Nietert, Paul J | Sutherland, Susan E | Bachman, David L | Keil, Julian E | de Boer, Ian H | Kizer, Jorge R | Psaty, Bruce M | Mukamal, Kenneth J | Nordestgaard, Børge G | Tybjærg-Hansen, Anne | Jensen, Gorm B | Schnohr, Peter | Giampaoli, Simona | Palmieri, Luigi | Panico, Salvatore | Pilotto, Lorenza | Vanuzzo, Diego | de la Cámara, Agustin Gómez | Simons, Leon A | Simons, Judith | McCallum, John | Friedlander, Yechiel | Gerry, F | Fowkes, R | Price, Jackie F | Lee, Amanda J | Taylor, James O | Guralnik, Jack M | Phillips, Caroline L | Wallace, Robert B | Kohout, Frank J | Cornoni-Huntley, Joan C | Guralnik, Jack M | Blazer, Dan G | Guralnik, Jack M | Phillips, Caroline L | Phillips, Caroline L | Guralnik, Jack M | Khaw, Kay-Tee | Wareham, Nicholas J | Brenner, Hermann | Schöttker, Ben | Müller, Heiko | Rothenbacher, Dietrich | Wennberg, Patrik | Jansson, Jan-Håkan | Nissinen, Aulikki | Donfrancesco, Chiara | Giampaoli, Simona | Woodward, Mark | Vartiainen, Erkki | Jousilahti, Pekka R | Harald, Kennet | Salomaa, Veikko | D'Agostino, Ralph B | Vasan, Ramachandran S | Fox, Caroline S | Pencina, Michael J | Daimon, Makoto | Oizumi, Toshihide | Kayama, Takamasa | Kato, Takeo | Bladbjerg, Else-Marie | Jørgensen, Torben | Møller, Lars | Jespersen, Jørgen | Dankner, Rachel | Chetrit, Angela | Lubin, Flora | Svärdsudd, Kurt | Eriksson, Henry | Welin, Lennart | Lappas, Georgios | Rosengren, Annika | Lappas, Georgios | Welin, Lennart | Svärdsudd, Kurt | Eriksson, Henry | Lappas, Georgios | Bengtsson, Calle | Lissner, Lauren | Björkelund, Cecilia | Cremer, Peter | Nagel, Dorothea | Strandberg, Timo E | Salomaa, Veikko | Tilvis, Reijo S | Miettinen, Tatu A | Tilvis, Reijo S | Strandberg, Timo E | Kiyohara, Yutaka | Arima, Hisatomi | Doi, Yasufumi | Ninomiya, Toshiharu | Rodriguez, Beatriz | Dekker, Jacqueline M | Nijpels, Giel | Stehouwer, Coen DA | Hu, Frank B | Sun, Qi | Rimm, Eric B | Willett, Walter C | Iso, Hiroyasu | Kitamura, Akihiko | Yamagishi, Kazumasa | Noda, Hiroyuki | Goldbourt, Uri | Vartiainen, Erkki | Jousilahti, Pekka R | Harald, Kennet | Salomaa, Veikko | Kauhanen, Jussi | Salonen, Jukka T | Kurl, Sudhir | Tuomainen, Tomi-Pekka | Poppelaars, Jan L | Deeg, Dorly JH | Visser, Marjolein | Meade, Tom W | De Stavola, Bianca Lucia | Hedblad, Bo | Nilsson, Peter | Engström, Gunnar | Verschuren, WM Monique | Blokstra, Anneke | de Boer, Ian H | Shea, Steven J | Meisinger, Christa | Thorand, Barbara | Koenig, Wolfgang | Döring, Angela | Verschuren, WM Monique | Blokstra, Anneke | Bueno-de-Mesquita, H Bas | Wilhelmsen, Lars | Rosengren, Annika | Lappas, Georgios | Fletcher, Astrid | Nitsch, Dorothea | Kuller, Lewis H | Grandits, Greg | Tverdal, Aage | Selmer, Randi | Nystad, Wenche | Mussolino, Michael | Gillum, Richard F | Hu, Frank B | Sun, Qi | Manson, JoAnn E | Rimm, Eric B | Hankinson, Susan E | Meade, Tom W | De Stavola, Bianca Lucia | Cooper, Jackie A | Bauer, Kenneth A | Davidson, Karina W | Kirkland, Susan | Shaffer, Jonathan A | Shimbo, Daichi | Kitamura, Akihiko | Iso, Hiroyasu | Sato, Shinichi | Holme, Ingar | Selmer, Randi | Tverdal, Aage | Nystad, Wenche | Nakagawa, Hidaeki | Miura, Katsuyuki | Sakurai, Masaru | Ducimetiere, Pierre | Jouven, Xavier | Bakker, Stephan JL | Gansevoort, Ron T | van der Harst, Pim | Hillege, Hans L | Crespo, Carlos J | Garcia-Palmieri, Mario R | Kee, Frank | Amouyel, Philippe | Arveiler, Dominique | Ferrières, Jean | Schulte, Helmut | Assmann, Gerd | Jukema, J Wouter | de Craen, Anton JM | Sattar, Naveed | Stott, David J | Cantin, Bernard | Lamarche, Benoît | Després, Jean-Pierre | Dagenais, Gilles R | Barrett-Connor, Elizabeth | Bergstrom, Jaclyn | Bettencourt, Richele R | Buisson, Catherine | Gudnason, Vilmundur | Aspelund, Thor | Sigurdsson, Gunnar | Thorsson, Bolli | Trevisan, Maurizio | Hofman, Albert | Ikram, M Arfan | Tiemeier, Henning | Witteman, Jacqueline CM | Tunstall-Pedoe, Hugh | Tavendale, Roger | Lowe, Gordon DO | Woodward, Mark | Devereux, Richard | Yeh, Jeun-Liang | Ali, Tauqeer | Calhoun, Darren | Ben-Shlomo, Yoav | Davey-Smith, George | Onat, Altan | Can, Günay | Nakagawa, Hidaeki | Sakurai, Masaru | Nakamura, Koshi | Morikawa, Yuko | Njølstad, Inger | Mathiesen, Ellisiv B | Løchen, Maja-Lisa | Wilsgaard, Tom | Sundström, Johan | Ingelsson, Erik | Michaëlsson, Karl | Cederholm, Tommy | Gaziano, J Michael | Buring, Julie | Ridker, Paul M | Gaziano, J Michael | Ridker, Paul M | Ulmer, Hanno | Diem, Günter | Concin, Hans | Rodeghiero, Francesco | Tosetto, Alberto | Wassertheil-Smoller, Sylvia | Manson, JoAnn E | Marmot, Michael | Clarke, Robert | Fletcher, Astrid | Brunner, Eric | Shipley, Martin | Kivimaki, Mika | Ridker, Paul M | Buring, Julie | Ford, Ian | Robertson, Michele | Ibañez, Alejandro Marín | Feskens, Edith | Geleijnse, Johanna M | Kromhout, Daan | Walker, Matthew | Watson, Sarah | Alexander, Myriam | Butterworth, Adam S | Angelantonio, Emanuele Di | Franco, Oscar H | Gao, Pei | Gobin, Reeta | Haycock, Philip | Kaptoge, Stephen | Seshasai, Sreenivasa R Kondapally | Lewington, Sarah | Pennells, Lisa | Rapsomaniki, Eleni | Sarwar, Nadeem | Thompson, Alexander | Thompson, Simon G | Walker, Matthew | Watson, Sarah | White, Ian R | Wood, Angela M | Wormser, David | Zhao, Xiaohui | Danesh, John
Background The extent to which adult height, a biomarker of the interplay of genetic endowment and early-life experiences, is related to risk of chronic diseases in adulthood is uncertain.
Methods We calculated hazard ratios (HRs) for height, assessed in increments of 6.5 cm, using individual–participant data on 174 374 deaths or major non-fatal vascular outcomes recorded among 1 085 949 people in 121 prospective studies.
Results For people born between 1900 and 1960, mean adult height increased 0.5–1 cm with each successive decade of birth. After adjustment for age, sex, smoking and year of birth, HRs per 6.5 cm greater height were 0.97 (95% confidence interval: 0.96–0.99) for death from any cause, 0.94 (0.93–0.96) for death from vascular causes, 1.04 (1.03–1.06) for death from cancer and 0.92 (0.90–0.94) for death from other causes. Height was negatively associated with death from coronary disease, stroke subtypes, heart failure, stomach and oral cancers, chronic obstructive pulmonary disease, mental disorders, liver disease and external causes. In contrast, height was positively associated with death from ruptured aortic aneurysm, pulmonary embolism, melanoma and cancers of the pancreas, endocrine and nervous systems, ovary, breast, prostate, colorectum, blood and lung. HRs per 6.5 cm greater height ranged from 1.26 (1.12–1.42) for risk of melanoma death to 0.84 (0.80–0.89) for risk of death from chronic obstructive pulmonary disease. HRs were not appreciably altered after further adjustment for adiposity, blood pressure, lipids, inflammation biomarkers, diabetes mellitus, alcohol consumption or socio-economic indicators.
Conclusion Adult height has directionally opposing relationships with risk of death from several different major causes of chronic diseases.
doi:10.1093/ije/dys086
PMCID: PMC3465767  PMID: 22825588
Height; cardiovascular disease; cancer; cause-specific mortality; epidemiological study; meta-analysis
2.  Insulin resistance and systemic inflammation, but not metabolic syndrome phenotype, predict 9 years mortality in older adults 
Atherosclerosis  2014;235(2):538-545.
Background
Although metabolic syndrome (MS) is a typical condition of middle-aged/older person, the association between MS and mortality risk has not been confirmed in people over 65 years. We hypothesized that while in the elderly MS phenotype might lose its value in predicting mortality risk, the two core factors of MS, i.e. insulin resistance (IR) and low-grade systemic inflammation (LGSI) would not.
Methods
1011 community-dwelling older individuals (InCHIANTI study) were included. MS phenotype was defined by NCEP-ATP-III criteria. IR was calculated by HOMA; high-sensitivity C-reactive protein was measured by ELISA. Subjects were divided into four groups based on presence/absence of IR (HOMA ≥2.27) and LGSI (hs-CRP ≥ 3g/L): Group 1: no IR/LGSI (reference); Group 2: LGSI only; Group 3: IR only; Group 4: IR+LGSI. Hazard Ratios (HR) for 9-years cardiovascular (CVD) and total mortality, according to IR/LGSI groups, were estimated in subjects with (n.311) and without MS by Cox model.
Results
31.8% of subjects with MS phenotype had no IR, 45.3% had no LGSI; moreover, 51% of subjects with both IR and LGSI didn’t display the MS phenotype. MS phenotype was not associated with CVD (HR:1.29; 95%C.I.:0.92–1.81) or total (HR:1.07; 95%C.I.:0.86–1.34) mortality risk, whereas the presence of IR plus LGSI was associated with increased CVD (no MS: HR 2.07, 95%CI:1.12–3.72; MS: HR 9.88, 95%CI:2.18–4), and overall (no MS: HR 1.72, 95%CI:1.001–3.17; MS: HR 1.51, 95%CI:1.02–2.28) mortality risk. The presence of IR (HR: 6.90, 95%CI:1.45–32) or LGSI (HR 7.56, 95%CI:1.63–35) was associated with CVD mortality, only among individuals with MS phenotype.
Conclusions
Among community dwelling older individuals, IR and LGSI, but not MS phenotype, was associated with 9-years overall and CVD mortality risk. Since a reduced “overlap” between MS phenotype and its physiopathological core (IR and LGSI) might be present with aging, we suggest that the definition of MS might be more holistic in advanced age, and probably comprise the measurement of IR and LGSI.
doi:10.1016/j.atherosclerosis.2014.05.959
PMCID: PMC4156965  PMID: 24956526
Insulin Resistance; C Reactive Protein; Mortality; Metabolic Syndrome; Elderly
3.  Social differences associated with the use of psychotropic drugs among men and women aged 65 to 74 years living in the community: the international mobility in aging study (IMIAS) 
BMC Geriatrics  2015;15:85.
Background
Elderly persons make greater use of psychotropic drugs, but there are few international studies on social differences in the use of these medications. The aim of this study is to examine social differences in the use of psychotropic drugs among persons aged 65–74 years in the International Mobility in Aging Study (IMIAS).
Methods
The sample consisted of 1,995 participants in the IMIAS 2012 baseline study in Saint-Hyacinthe (Canada), Kingston (Canada), Tirana (Albania), Manizales (Colombia), and Natal (Brazil). During home visits, all medication taken by the participants in the previous 15 days was recorded. We then used the Anatomical Therapeutic Chemical classification system to code psychotropic drugs as anxiolytics, sedatives, hypnotics (ASH); antidepressants (ADP); or analgesics, antiepileptics, or antiparkinsonians (AEP). Prevalence ratios for psychotropic drug use according to sex, education, income, and occupation were estimated by fitting a Poisson regression and controlling for demographic and health covariates.
Results
Psychotropic drug use was higher among Canadian participants than among those living outside Canada. Prevalence of AEP drug use was higher for women than men in the Canadian and Latin American sites. In Tirana, antidepressant drugs were rarely used. Socioeconomic differences varied among sites. In the Canadian cities, low socioeconomic standing was associated with higher frequency of psychotropic drug use. In the Latin American cities, elderly people with high education and income levels showed a higher level of antidepressant drug use, while people with manual occupations had a higher use of AEP drugs. In Tirana, ASH drug use was higher among those with low income.
Conclusion
An inverse association was observed between socioeconomic standing and psychotropic drug use in Canada, while the opposite was true in Latin America. Albania was notable for an absence of antidepressant use and greater use of ASH drugs among low-income groups.
doi:10.1186/s12877-015-0083-3
PMCID: PMC4506764  PMID: 26188649
Psychotropic drugs; Aging; Social differences; Latin America; Canada; Albania
4.  The Prognostic Value of Repeated Measures of Lower Extremity Performance: Should We Measure More Than Once? 
Background.
Lower extremity physical performance measured at one point in time is a powerful predictor of future disability. Whether information on previous lower extremity performance adds independent information to disability prediction compared to a single measure alone is unknown.
Methods.
Data are from community-dwelling men and women aged greater than or equal to 65 years enrolled in the Invecchiare in Chianti study who were free of mobility and activities of daily living (ADL) disability at baseline and at 3-year follow-up (n = 891). Walking speed and Short Physical Performance Battery were examined at baseline and at the 3-year follow-up (zero-time). Logistic regression analysis was used to examine the associations between physical performance measures and incident mobility and ADL disability detected at the 6-year and 9-year follow-up.
Results.
Walking speed and Short Physical Performance Battery score assessed at the zero-time strongly predicted development of mobility and ADL disability during the subsequent 6 years independent of walking speed/Short Physical Performance Battery score 3 years prior.
Conclusions.
Current lower extremity performance is a strong risk factor for subsequent mobility and ADL disability and is independent of performance 3 years prior, which has negligible independent prognostic value.
doi:10.1093/gerona/glt175
PMCID: PMC4067114  PMID: 24270061
Aging; Disability; Measurement; Mobility; Physical performance; Walking speed.
6.  Pain Characteristics Associated With the Onset of Disability in Older Adults: The MOBILIZE Boston Study 
Background/Objectives
To determine the effects of chronic pain on the development of disability and decline in physical performance over time among older adults.
Design
Longitudinal cohort study with 18 months follow-up.
Setting
Urban/suburban communities
Participants
634 community-dwelling older adults aged >64 years.
Measurements
Chronic pain assessment consisted of musculoskeletal pain locations, and pain severity and pain interference by subscales of the Brief Pain Inventory. Disability was self-reported as any difficulty in mobility and basic and instrumental activities of daily living (ADL, IADL). Mobility performance was measured using the Short Physical Performance Battery (SPPB). Relationships between baseline pain and incident disability in 18 months were determined using risk ratios (RRs) from multivariable Poisson regression models.
Results
Almost 65% of participants reported chronic musculoskeletal pain at baseline. New onset of mobility difficulty at 18-months was strongly associated with baseline pain distribution: 7% (no sites), 18% (1 site), 24% (multisite) and 39% (widespread pain, p-value for trend <0.001). Similar graded effects were found for other disability measures. Elders with multisite or widespread pain had at least a three-fold increased risk for onset of mobility difficulty compared to their peers without pain after adjusting for disability risk factors (multisite pain: RR=2.95, 95%CI, 1.58–5.50; widespread pain: RR=3.57, 95%CI, 1.71–7.48). Widespread pain contributed to decline in mobility performance (1 point decline in SPPB, RR=1.47, 95%CI, 1.08–2.01). Similar associations were found for baseline pain interference predicting subsequent mobility decline and (I)ADL disability. Weaker and less consistent associations were observed with pain severity.
Conclusion
Older community-dwelling adults living with chronic pain in multiple musculoskeletal locations have a substantial increased risk for developing disability over time and for clinically meaningful decline in mobility performance.
doi:10.1111/jgs.12848
PMCID: PMC4057984  PMID: 24823985
widespread chronic pain; older adults; mobility limitation; activities of daily living
7.  Prevalence and Clinical Correlates of Sarcopenia in Community-Dwelling Older People: Application of the EWGSOP Definition and Diagnostic Algorithm 
Background.
Muscle impairment is a common condition in older people and a powerful risk factor for disability and mortality. The aim of this study was to apply the European Working Group on Sarcopenia in Older People criteria to estimate the prevalence and investigate the clinical correlates of sarcopenia, in a sample of Italian community-dwelling older people.
Methods.
Cross-sectional analysis of 730 participants (74% aged 65 years and older) enrolled in the InCHIANTI study. Sarcopenia was defined according to the European Working Group on Sarcopenia in Older People criteria using bioimpedance analysis for muscle mass assessment. Logistic regression analysis was used to identify the factors independently associated with sarcopenia.
Results.
Sarcopenia defined by the European Working Group on Sarcopenia in Older People criteria increased steeply with age (p < .001), with 31.6% of women and 17.4% of men aged 80 years or older being affected by this condition. Higher education (odds ratio: 0.85; 95% CI: 0.74–0.98), lower insulin-like growth factor I (lowest vs highest tertile, odds ratio: 3.89; 95% CI: 1.03–14.1), and low bioavailable testosterone (odds ratio: 2.67; 95% CI: 1.31–5.44) were independently associated with the likelihood of being sarcopenic. Nutritional intake, physical activity, and level of comorbidity were not associated with sarcopenia.
Conclusions.
Sarcopenia identified by the European Working Group on Sarcopenia in Older People criteria is a relatively common condition in Italian octogenarians, and its prevalence increases with aging. Correlates of sarcopenia identified in this study might suggest new approaches for prevention and treatment of sarcopenia.
doi:10.1093/gerona/glt149
PMCID: PMC3968828  PMID: 24085400
Sarcopenia; Community-dwelling older people; Frail elderly.
8.  The association between leptin and depressive symptoms is modulated by abdominal adiposity 
Psychoneuroendocrinology  2014;42:1-10.
Background
Evidence for a role of leptin in depression is limited and conflicting. Inconclusive findings may be explained by the complex effect of obesity on leptin signaling. In particular, both hyperleptinemia due to leptin resistance in obese persons as well as low leptin in lean persons can imply that low leptin biological signaling is associated with an increased risk of significant depressive symptoms. We tested whether the relationship between leptin and depressive symptoms is modulated by abdominal adiposity in two population-based studies.
Methods
Data were from 851 participants (65–94 years) of the InCHIANTI Study and 1,064 (26–93 years) of the Baltimore Longitudinal Study of Aging (BLSA). Plasma concentrations of leptin, waist circumference and depressive symptoms via the Center for Epidemiological Studies-Depression scale (CES-D) were assessed. In longitudinal InCHIANTI analyses onset of depressed mood (CES-D≥20) was evaluated over a 9-year follow-up.
Results
In pooled cross-sectional analyses the interaction between leptin and waist circumference was significantly associated with CES-D scores ((log)leptin-by-waist interaction p=0.01). Also in longitudinal analyses, the (log)leptin-by-waist interaction term significantly (p=0.04) predicted depressed mood onset over time; depressed mood risk was especially increased for high levels of both leptin and waist circumference.
Conclusions
The present findings suggest that low leptin signaling rather than low leptin concentration is a risk factor for depression. Future studies should develop proxy measures of leptin signaling by combining information on abdominal adiposity and leptin level to be used for clinical and research applications.
doi:10.1016/j.psyneuen.2013.12.015
PMCID: PMC4214922  PMID: 24636496
leptin; depression; abdominal adiposity; obesity; aging
9.  The relationship of physical performance with HIV disease and mortality 
AIDS (London, England)  2014;28(18):2711-2719.
Objective
To evaluate whether HIV infection was associated with reduced physical performance, and to examine if reduced physical performance predicted mortality in our aging cohort of HIV-infected and HIV-uninfected persons.
Design
Prospective, observational cohort of current and former injection drug users in the AIDS Linked to the IntraVenous Experience study in Baltimore, Maryland, USA.
Methods
The Short Physical Performance Battery (SPPB) was used as an objective measure of physical performance and measured semiannually along with behavioral and demographic data. Correlates of reduced physical performance (SPPB score ≤10) were identified and the relationship between reduced physical performance, HIV infection and mortality was analyzed by Cox regression.
Results
Among 12 270 person-visits contributed by 1627 participants, the median age was 51, 30.3% were HIV-infected and 32.6% had an SPPB score 10 or less. In multivariable models, HIV infection was independently associated with 30% increased odds of reduced physical performance [odds ratio 1.30; 95% confidence interval (CI):1.12–1.52]. Reduced physical performance predicted mortality in a dose-response manner and within all HIV disease strata. Whereas reduced physical performance alone (hazard ratio 2.52, 95% CI: 1.59–4.00) and HIV infection alone (hazard ratio 2.78, 95% CI: 1.70–4.54) increased mortality, HIV-infected participants with reduced physical performance had a six-fold increased mortality risk (hazard ratio 6.03, 95% CI: 3.80–10.0) compared with HIV-uninfected participants with higher physical performance.
Conclusion
HIV infection was independently associated with reduced physical performance. HIV and reduced physical performance have independent and joint effects on mortality. Physical performance measurement may be an important research and clinical tool to predict adverse outcomes among aging HIV-infected persons.
doi:10.1097/QAD.0000000000000507
PMCID: PMC4380225  PMID: 25493597
aging; HIV; injection drug use; mortality; physical function
10.  Motoric cognitive risk syndrome 
Neurology  2014;83(8):718-726.
Objectives:
Our objective is to report prevalence of motoric cognitive risk syndrome (MCR), a newly described predementia syndrome characterized by slow gait and cognitive complaints, in multiple countries, and its association with dementia risk.
Methods:
Pooled MCR prevalence analysis of individual data from 26,802 adults without dementia and disability aged 60 years and older from 22 cohorts from 17 countries. We also examined risk of incident cognitive impairment (Mini-Mental State Examination decline ≥4 points) and dementia associated with MCR in 4,812 individuals without dementia with baseline Mini-Mental State Examination scores ≥25 from 4 prospective cohort studies using Cox models adjusted for potential confounders.
Results:
At baseline, 2,808 of the 26,802 participants met MCR criteria. Pooled MCR prevalence was 9.7% (95% confidence interval [CI] 8.2%–11.2%). MCR prevalence was higher with older age but there were no sex differences. MCR predicted risk of developing incident cognitive impairment in the pooled sample (adjusted hazard ratio [aHR] 2.0, 95% CI 1.7–2.4); aHRs were 1.5 to 2.7 in the individual cohorts. MCR also predicted dementia in the pooled sample (aHR 1.9, 95% CI 1.5–2.3). The results persisted even after excluding participants with possible cognitive impairment, accounting for early dementia, and diagnostic overlap with other predementia syndromes.
Conclusion:
MCR is common in older adults, and is a strong and early risk factor for cognitive decline. This clinical approach can be easily applied to identify high-risk seniors in a wide variety of settings.
doi:10.1212/WNL.0000000000000717
PMCID: PMC4150127  PMID: 25031288
11.  What Physical Attributes Underlie Self-Reported vs. Observed Ability to Walk 400 m in Later Life? 
Objective
The aims of this study were to evaluate and contrast the physical attributes that are associated with self-reported vs. observed ability to walk 400 m among older adults.
Design
Analysis of baseline and 3-yr data from 1026 participants 65 yrs or older in the InCHIANTI (Invecchiare in Chianti) study was conducted. Observed and self-reported ability to walk 400 m at baseline and at 3 yrs were primary outcomes. Predictors included leg speed, leg strength, leg strength symmetry, range of motion, balance, and kyphosis.
Results
Balance, leg speed, leg strength, kyphosis, leg strength symmetry, and knee range of motion were associated with self-reported ability to walk 400 m at baseline (P < 0.001, c = 0.85). Balance, leg speed, and knee range of motion were associated with observed 400-m walk (P < 0.001, c = 0.85) at baseline. Prospectively, baseline leg speed and leg strength were predictive of both self-reported (P < 0.001, c = 0.79) and observed (P < 0.001, c = 0.72) ability to walk 400 m at 3 yrs.
Conclusions
The profiles of attributes that are associated with self-reported vs. observed walking ability differ. The factor most consistently associated with current and future walking ability is leg speed. These results draw attention to important foci for rehabilitation.
doi:10.1097/PHM.0000000000000034
PMCID: PMC4304676  PMID: 24322434
Physical Performance; Rehabilitation; Successful Aging; Mobility Limitation
12.  Sensorimotor and psychosocial determinants of 3-year incident mobility disability in middle-aged and older adults 
Age and Ageing  2014;43(1):64-69.
Objective: to identify sensorimotor and psychosocial determinants of 3-year incident mobility disability.
Design: prospective.
Setting: population-based sample of community-dwelling older persons.
Participants: community-living middle-aged and older persons (age: 50–85 years) without baseline mobility disability (n = 622).
Measurements: mobility disability, defined as self-reported inability to walk a quarter mile without resting or inability to walk up a flight of stairs unsupported, was ascertained at baseline and 3-year follow-up. Potential baseline determinant characteristics included demographics, education, social support, financial condition, knee extensor strength, visual contrast sensitivity, cognition, depression, presence of chronic conditions and history of falls.
Results: a total of 13.5% participant reported 3-year incident mobility disability. Age ≥75 years, female sex, knee extensor strength in the lowest quartile, visual contrast sensitivity <1.7 on the Pelli-Robson chart or significant depressive symptoms (CESD score >16) were independent determinants of 3-year incident mobility disability (ORs 1.84–16.51).
Conclusions: low visual contrast sensitivity, poor knee extensor strength and significant depressive symptoms are independent determinants of future onset of mobility disability.
doi:10.1093/ageing/aft135
PMCID: PMC3861339  PMID: 24042004
mobility; disability; depression; vision; muscle strength; older people
13.  Effect of structured physical activity on prevention of major mobility disability in older adults: the LIFE Study randomized clinical trial 
JAMA  2014;311(23):2387-2396.
SUMMARY
Importance
In older adults reduced mobility is common and is an independent risk factor for morbidity, hospitalization, disability, and mortality. Limited evidence suggests that physical activity may help prevent mobility disability; however, there are no definitive clinical trials examining if physical activity prevents or delays mobility disability.
Objective
To test the hypothesis that a long-term structured physical activity program is more effective than a health education program (also referred to as a successful aging program) in reducing the risk of major mobility disability.
Design, Setting, and Participants
The Lifestyle Interventions and Independence for Elders (LIFE) study was a multicenter, randomized trial that enrolled participants between February 2010 and December 2011, who participated for an average of 2.6 years. Follow-up ended in December 2013. Outcome assessors were blinded to the intervention assignment. Participants were recruited from urban, suburban and rural communities at 8 field centers throughout the US. We randomized a volunteer sample of 1,635 sedentary men and women aged 70–89 years who had physical limitations, defined as a score on the Short Physical Performance Battery of 9 or below, but were able to walk 400 m.
Interventions
Participants were randomized to a structured moderate intensity physical activity program (n=818) done in a center and at home that included including aerobic, resistance and flexibility training activities or to a health education program (n=817) consisting of workshops on topics relevant to older adults and upper extremity stretching exercises.
Main Outcomes and Measures
The primary outcome was major mobility disability objectively defined by loss of ability to walk 400 m.
Results
Incident major mobility disability occurred in 30.1% (n=246/818) of physical activity and 35.5% (n=290/817) of health education participants (HR=0.82, 95%CI=0.69–0.98, p=0.03). Persistent mobility disability was experienced by 120/818 (14.7%) physical activity and 162/817 (19.8%) health education participants (HR=0.72; 95%CI=0.57–0.91; p=0.006). Serious adverse events were reported by 404/818 (49.4%) of the physical activity and 373/817 (45.7%) of the health education participants (Risk Ratio=1.08; 95%CI=0.98–1.20).
Conclusions and Relevance
A structured moderate intensity physical activity program, compared with a health education program, reduced major mobility disability over 2.6 years among older adults at risk of disability. These findings suggest mobility benefit from such a program in vulnerable older adults.
Registration
ClinicalsTrials.gov identifier NCT01072500.
doi:10.1001/jama.2014.5616
PMCID: PMC4266388  PMID: 24866862
14.  Lifestyle Interventions and Independence for Elders Study: Recruitment and Baseline Characteristics 
Background.
Recruitment of older adults into long-term clinical trials involving behavioral interventions is a significant challenge. The Lifestyle Interventions and Independence for Elders (LIFE) Study is a Phase 3 multicenter randomized controlled multisite trial, designed to compare the effects of a moderate-intensity physical activity program with a successful aging health education program on the incidence of major mobility disability (the inability to walk 400 m) in sedentary adults aged 70–89 years, who were at high risk for mobility disability (scoring ≤9 on the Short Physical Performance Battery) at baseline.
Methods.
Recruitment methods, yields, efficiency, and costs are described together with a summary of participant baseline characteristics. Yields were examined across levels of sex, race and ethnicity, and Short Physical Performance Battery, as well as by site.
Results.
The 21-month recruiting period resulted in 14,812 telephone screens; 1,635 participants were randomized (67.2% women, 21.0% minorities, 44.7% with Short Physical Performance Battery scores ≤7). Of the telephone-screened participants, 37.6% were excluded primarily because of regular participation in physical activity, health exclusions, or self-reported mobility disability. Direct mailing was the most productive recruitment strategy (59.5% of randomized participants). Recruitment costs were $840 per randomized participant. Yields differed by sex and Short Physical Performance Battery. We accrued 11% more participant follow-up time than expected during the recruitment period as a result of the accelerated recruitment rate.
Conclusions.
The LIFE Study achieved all recruitment benchmarks. Bulk mailing is an efficient method for recruiting high-risk community-dwelling older persons (including minorities), from diverse geographic areas for this long-term behavioral trial.
doi:10.1093/gerona/glt064
PMCID: PMC3814232  PMID: 23716501
Mobile disability; Older adults; Physical activity; Minority recruitment; Randomized controlled trial.
15.  The MAT-sf: Clinical Relevance and Validity 
Background.
The measurement of mobility is essential to both aging research and clinical practice. A newly developed self-report measure of mobility, the mobility assessment tool—short form (MAT-sf), uses video animations to improve measurement accuracy/precision. Using a large baseline data set, we recalibrated the items, evaluated the extent to which older patients’ self-efficacy (i.e., confidence) for walking was related to MAT-sf scores beyond their actual 400-m walk time, and assessed the relationship of the MAT-sf with body mass index and other clinical variables.
Methods.
The analyses employed baseline data from the Lifestyle Interventions and Independence for Elders Study.
Results.
Item recalibration demonstrated that the MAT-sf scoring algorithm was robust. In an analysis with 400-m walk time and self-efficacy regressed on the MAT-sf, both variables shared unique variance with the MAT-sf (p < .001). The MAT-sf was inversely related to several comorbidities, most notably hypertension and arthritis (p < .001), and scores were lowest when body mass index ≥ 35kg/m2. Finally, MAT-sf scores were directly related to Short Physical Performance Battery scores, inversely related to difficulty with activities of daily living (p < .001) and higher for men than for women (p < .001).
Conclusions.
The findings extend the validity and clinical utility of this innovative tool for assessing self-reported mobility in older adults. Longitudinal data on the MAT-sf from the Lifestyle Interventions and Independence for Elders Study will enable us to evaluate the relative contributions of self-report and performance-based measures of mobility on important health outcomes.
doi:10.1093/gerona/glt068
PMCID: PMC3814234  PMID: 23685766
Mobility; Geriatric assessment; Physical function; MAT-sf
16.  Prevalence and Impact of Pain among Older Adults in the United States: Findings from the 2011 National Health and Aging Trends Study 
Pain  2013;154(12):10.1016/j.pain.2013.07.029.
The study sought to determine the prevalence and impact of pain in a nationally representative sample of older adults in the United States (US). Data from the 2011 National Health and Aging Trends Study were analyzed. In-person interviews were conducted in 7,601 adults ages ≥65 years. The response rate was 71.0% and all analyses were weighted to account for the sampling design. The overall prevalence of bothersome pain in the last month was 52.9%, afflicting 18.7 million older adults in the US. Pain did not vary across age groups (P=0.21) and this pattern remained unchanged when accounting for cognitive performance, dementia, proxy-responses, and residential care living status. Pain prevalence was higher in women and in older adults with obesity, musculoskeletal conditions, and depressive symptoms (P<0.001). The majority (74.9%) of older adults with pain endorsed multiple sites of pain. Several measures of physical capacity, including grip strength and lower extremity physical performance, were associated with pain and multisite pain. For example, self-reported inability to walk 3 blocks was 72% higher in participants with than without pain [adjusted Prevalence Ratio=1.72 (95% Confidence Interval: 1.56–1.90)]. Participants with 1, 2, 3, and >4 sites of pain had gait speeds that were 0.01, 0.03, 0.05, and 0.08 meters per second slower, respectively, than older adults without pain, adjusting for disease burden and other confounders (P<0.001). In summary, bothersome pain in the last month was reported by half of the older adult population of the US in 2011 and was strongly associated with decreased physical function.
doi:10.1016/j.pain.2013.07.029
PMCID: PMC3843850  PMID: 24287107
pain; aging; geriatric assessment; locomotor activity; prevalence study
17.  Aging, the Central Nervous System, and Mobility 
Background.
Mobility limitations are common and hazardous in community-dwelling older adults but are largely understudied, particularly regarding the role of the central nervous system (CNS). This has limited development of clearly defined pathophysiology, clinical terminology, and effective treatments. Understanding how changes in the CNS contribute to mobility limitations has the potential to inform future intervention studies.
Methods.
A conference series was launched at the 2012 conference of the Gerontological Society of America in collaboration with the National Institute on Aging and the University of Pittsburgh. The overarching goal of the conference series is to facilitate the translation of research results into interventions that improve mobility for older adults.
Results.
Evidence from basic, clinical, and epidemiological studies supports the CNS as an important contributor to mobility limitations in older adults without overt neurologic disease. Three main goals for future work that emerged were as follows: (a) develop models of mobility limitations in older adults that differentiate aging from disease-related processes and that fully integrate CNS with musculoskeletal contributors; (b) quantify the contribution of the CNS to mobility loss in older adults in the absence of overt neurologic diseases; (c) promote cross-disciplinary collaboration to generate new ideas and address current methodological issues and barriers, including real-world mobility measures and life-course approaches.
Conclusions.
In addition to greater cross-disciplinary research, there is a need for new approaches to training clinicians and investigators, which integrate concepts and methodologies from individual disciplines, focus on emerging methodologies, and prepare investigators to assess complex, multisystem associations.
doi:10.1093/gerona/glt089
PMCID: PMC3805295  PMID: 23843270
Motor control; Central nervous system; Mobility.
18.  PROGENITOR CELL RELEASE PLUS EXERCISE TO IMPROVE FUNCTIONAL PERFORMANCE IN PERIPHERAL ARTERY DISEASE: THE PROPEL STUDY 
Contemporary clinical trials  2013;36(2):502-509.
Functional impairment, functional decline, and mobility loss are major public health problems in people with lower extremity peripheral artery disease (PAD). Few medical therapies significantly improve walking performance in PAD. We describe methods for the PROgenitor cell release Plus Exercise to improve functionaL performance in PAD (PROPEL) Study, a randomized controlled clinical trial designed to determine whether granulocyte-macrophage colony stimulating factor (GM-CSF) combined with supervised treadmill walking exercise improves six-minute walk distance more than GM-CSF alone, more than supervised treadmill exercise alone, and more than placebo plus attention control in participants with PAD, respectively. PROPEL Study participants are randomized to one of four arms in a 2 by 2 factorial design. The four study arms are GM-CSF plus supervised treadmill exercise, GM-CSF plus attention control, placebo plus supervised exercise therapy, or placebo plus attention control. The primary outcome is change in six-minute walk distance at 12-week follow-up. Secondary outcomes include change in brachial artery flow-mediated dilation (FMD), change in maximal treadmill walking time, and change in circulating CD34+ cells at 12-week follow-up. Outcomes are also measured at six-week and six-month follow-up. Results of the PROPEL Study will have important implications for understanding mechanisms of improving walking performance and preventing mobility loss in the large and growing number of men and women with PAD.
doi:10.1016/j.cct.2013.09.011
PMCID: PMC3939047  PMID: 24080099
19.  Association of Inflammation With Loss Of Ability to Walk 400 Meters: Longitudinal Findings From the Inchianti Study 
Objectives
To examine relationships between eight markers of inflammation (interleukin [IL]-6, IL-6 receptor [R], C-reactive protein [CRP], tumor necrosis factor [TNF]-α, TNF receptor 1[R1], TNFR2, IL-1 receptor antagonist, IL-18) and incident loss of ability to walk 400 m.
Design
Prospective cohort study.
Setting
Older adults enrolled in the InvecchiareInChianti Study.
Participants
One thousand six community-dwelling participants aged 65+.
Measurements
The eight inflammatory markers were measured at baseline, and an inflammation score was calculated based on the number of inflammatory markers for which the participant was in the highest quartile. Incidence of mobility disability was determined among participants able to walk 400 m at baseline. Logistic regression models were used to determine whether each of the inflammatory markers and the inflammation score predicts loss of the ability to walk 400 m at six-year follow-up.
Results
After adjusting for covariates, individuals with aTNFR1 level in each of the top 3 quartiles (Q2, 3, 4) were more likely to be unable to walk 400 m at follow-up compared to those with TNFR1 levels in Q1. When adjusting for the same covariates, participants with an inflammation score of 3 or 4 were more likely to become unable to complete the 400 m walk at follow-up compared to participants with a score of 0.
Conclusion
These results bring additional evidence to the notion that inflammation is implicated in the mechanisms that cause incident mobility disability and suggest that a combined measure of inflammatory markers may improve our prediction of functional prognosis.
doi:10.1111/jgs.12446
PMCID: PMC3801413  PMID: 24083386
inflammation; mobility; 400 m walk; functional limitation; aging
20.  Long-term Survival in Adults Aged 65 and Older With White Matter Hyperintensity: Association With Performance on the Digit Symbol Substitution Test 
Psychosomatic medicine  2013;75(7):10.1097/PSY.0b013e31829c1df2.
OBJECTIVE
White matter hyperintensity (WMH) confers increased mortality risk in patients with cardiovascular diseases. However, little is known about differences in survival times among adults 65 years and older who have WMH and live in the community. To characterize the factors that may reduce mortality risk in the presence of WMH, measures of race, sex, ApoE4, neuroimaging, cardiometabolic, physiological and psychosocial characteristics were examined, with a particular focus on information processing as measured by the Digit Symbol Substitution Test(DSST).
METHODS
Cox-proportional models were used to estimate mortality risks in a cohort of 3513 adults (74.8years, 58%women, 84%white) with WMH (0–9 points), DSST (0–90 points), risk factor assessment in 1992–94 and data on mortality and incident stroke to 2009 (median follow-up [range]:14.2[0.5–18.1]years).
RESULTS
WMH predicted a 48% greater mortality risk (age-adjusted hazard ratio (HR)[95% confidence interval(CI)] for WMH>3 points=1.48[1.35–1.62]). This association was attenuated after adjustment for DSST (HR[CI]: 1.38[1.27–1.51]) or lacunar infarcts (HR[CI]: 1.37[1.25,1.50]) but not after adjustment for other factors. The interaction between DSST and WMH was significant (p=0.011). In fully adjusted models stratified by WMH>3, participants with DSST>median had a 34% lower mortality risk among those with WMH>3 (n=532/1217) and a 28% lower mortality risk among those with WMH<3 (n=1364/2296), compared to participants with DSST
CONCLUSION
WMH is associated with increased long-term mortality risk in community-dwelling adults aged 65 and older. The increased risk is attenuated for those with higher DSST. Assessment of cognitive function with DSST may improve risk stratification of individuals with WMH.
doi:10.1097/PSY.0b013e31829c1df2
PMCID: PMC3809761  PMID: 23886735
mortality; information processing; white matter hyperintensity
PLoS ONE  2014;9(8):e102299.
Background
This study examines the associations between lifecourse adversity and physical performance in old age in different societies of North and South America and Europe.
Methods
We used data from the baseline survey of the International Study of Mobility in Aging, conducted in: Kingston (Canada), Saint-Hyacinthe (Canada), Natal (Brazil), Manizales (Colombia) and Tirana (Albania). The study population was composed of community dwelling people between 65 and 74 years of age, recruiting 200 men and 200 women at each site. Physical Performance was assessed with the Short Physical Performance Battery (SPPB). Economic and social adversity was estimated from childhood adverse events, low education, semi-skilled occupations during adulthood and living alone and insufficient income in old age.
Results
A total of 1995 people were assessed. Low physical performance was associated with childhood social and economic adversity, semi-skilled occupations, living alone and insufficient income. Physical performance was lower in participants living in Colombia, Brazil and Albania than in Canada counterparts, despite adjustment for lifecourse adversity, age and sex.
Conclusions
We show evidence of the early origins of social and economic inequalities in physical performance during old age in distinct populations and for the independent and cumulative disadvantage of low socioeconomic status during adulthood and poverty and living alone in later life.
doi:10.1371/journal.pone.0102299
PMCID: PMC4125146  PMID: 25101981
This study examined if inability to perform adaptive locomotor tests predicts self-reported incident mobility disability. InCHIANTI study participants (n=611, age: 50–85 years) who could walk 7 m at self-selected speed and had no self-reported mobility disability at baseline were included. Ability to complete 4 adaptive locomotor tests was assessed: fast walking, walking on a narrow path, crossing obstacles while walking and talking while walking. Mobility disability was recorded again at 3-year follow-up. Failure in fast walking and narrow-path walking tests predicted ~2.5 times likelihood of reporting incident mobility disability (p=0.009 and 0.011, respectively). Failure in obstacle crossing test predicted ~2 times likelihood of reporting incident mobility disability, however, this result did not reach statistical significance (p=0.077). Failure in talking while walking did not predict incident mobility disability. Those who failed both fast walking and narrow-path walking tests were almost 9 times as likely to report incident mobility disability.
doi:10.1097/PHM.0b013e31827d634e
PMCID: PMC3632651  PMID: 23291600
Mobility; Disability; Aging
BACKGROUND
Higher intake of fruits and vegetables appears to protect against inflammation, poor physical performance, and disability, but their relationship with muscle strength is unclear. We examined the association between total plasma carotenoids, an indicator of fruit and vegetable intake, and changes in muscle strength over a 6-year follow-up in the participants aged 65 years and older in the InCHIANTI study, a population-based study in Tuscany, Italy.
METHODS
Plasma carotenoids were measured at enrollment (1998–2000). Hip, knee and grip strength were measured at enrollment and 6 years later (2004–2006) in 628 of the 948 participants evaluated at baseline. Poor muscle strength was defined as the lowest sex-specific quartile of hip, knee and grip strength at enrollment. The main outcome was poor muscle strength at the six-year follow-up visit among those originally in the upper three quartiles of strength at enrollment.
RESULTS
Overall, 24.9% (110/441), 25.0% (111/444) and 24.9% (118/474) participants developed poor hip, knee and grip strength, respectively. After adjusting for potential confounders, participants in the lowest vs. the highest quartile of total plasma carotenoids at enrollment were at higher risk of developing poor hip (O.R. 2.25, 95% C.I. 1.13–4.48, P = 0.02), knee (O.R. 2.12, 95% C.I. 1.08–4.09, P = 0.03) and grip (O.R. 1.85, 95% C.I. 0.95–3.61, P = 0.07) muscle strength at the six-year follow-up visit.
CONCLUSION
These findings suggest that older community-dwelling adults with lower plasma carotenoids levels, a marker of poor fruit and vegetable intake, are at a higher risk of decline in skeletal muscle strength over time.
PMCID: PMC4101895  PMID: 18426961
carotenoids; InCHIANTI study; fruit; vegetable; sarcopenia
Frailty is a clinical state in which there is an increase in an individual’s vulnerability for developing increased dependency and/or mortality when exposed to a stressor. Frailty can occur as the result of a range of diseases and medical conditions. A consensus group consisting of delegates from 6 major international, European, and US societies created 4 major consensus points on a specific form of frailty: physical frailty. Physical frailty is an important medical syndrome. The group defined physical frailty as “a medical syndrome with multiple causes and contributors that is characterized by diminished strength, endurance, and reduced physiologic function that increases an individual’s vulnerability for developing increased dependency and/or death.”Physical frailty can potentially be prevented or treated with specific modalities, such as exercise, protein-calorie supplementation, vitamin D, and reduction of polypharmacy.Simple, rapid screening tests have been developed and validated, such as the simple FRAIL scale, to allow physicians to objectively recognize frail persons.For the purposes of optimally managing individuals with physical frailty, all persons older than 70 years and all individuals with significant weight loss (≥5%) due to chronic disease should be screened for frailty.
doi:10.1016/j.jamda.2013.03.022
PMCID: PMC4084863  PMID: 23764209
Frailty; physical frailty; rapid screening tests; weight loss; comorbidities
Background
Common variation at chromosome 9p21 (marked by rs10757278 or rs1333049) is associated with coronary artery disease (CAD) and peripheral vascular disease. A decreasing effect at older age was suggested, and effects on long-term mortality are unclear. We estimated 9p21 associations with CAD and all-cause mortality in a CAD diagnosis–free older population. We also estimated classification gains on adding the variant to the Framingham Risk Score (FRS) for CAD.
Methods and Results
DNA was from an Established Populations for Epidemiological Study of the Elderly–Iowa cohort from 1988 (participants >71 years), with death certificates obtained to 2008 for 92% of participants. Cox regression models were adjusted for confounders and CAD risk factors. Of 1095 CAD diagnosis–free participants, 52% were heterozygous (CG) and 22% were homozygous (CC) for the risk C allele rs1333049. Unadjusted CAD-attributed death rates in the CC group were 30 vs 22 per 1000 person-years for the GG group. The C allele was associated with all-cause (hazard ratio, 1.19; 95% CI, 1.08–1.30) and CAD (hazard ratio, 1.29; 95% CI, 1.08–1.56) mortality, independent of CAD risk factors. There was no association with stroke deaths. Variant associations with CAD mortality were attenuated after the age of 80 years (age-interaction term P=0.05). In age group 71 to 80 years, FRS classified as high risk 21% of respondents who died of CAD within 10 years; adding 9p21 identified 27% of respondents.
Conclusions
In 71- to 80-year-old subjects free of CAD diagnoses, 9p21 is associated with excess mortality, mainly attributed to CAD mortality. Adding 9p21 to the FRS may improve the targeting of CAD prevention in older people, but validation in independent samples is needed for confirmation.
doi:10.1161/CIRCGENETICS.111.960146
PMCID: PMC4053863  PMID: 21852414
coronary artery disease; genetic variation; myocardial infarction; survival; Framingham Risk Score

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