Genetic and cardiovascular risk factors in relation to physical - PowerPoint PPT Presentation

Genetic and cardiovascular risk factors in relation to physical limitation Emerald G. Heiland, PhD candidate Aging Research Center, Karolinska Institutet, Stockholm, Sweden Emerald.heiland@ki.se

CONFLICT OF INTEREST DISCLOSURE I have no potential conflict of interest to report

Verghese et al. APOE ε 4 allele Lancet Neurol 2011; Bertram et al. Nat Genet 2007 Haan et al. Curr Cardiovasc Risk Rep 2010 3

APOE ε 4 and physical function limitation in longitudinal studies- inconsistent results Grip strength Grip strength Skoog et al. Front Aging Neurosci 2016 Walking speed Chair stand Balance Grip strength Alfred et al. AGE 2014 Walking speed decline Get up and go/walking speed Chair stand Balance Walking speed decline in men Walking speed decline Verghese et al. Gerontology 2013 Disability Melzer et al. Gerontology 2005 Walking speed Chair stand Chair stand

Cardiovascular risk factors (CRFs) and mobility limitations N o n  4 c a rrie rs  4 C a rrie rs 8 O d d s R a tio (9 5 % C I) 4 2 1 0 .5  2  2 0 1 0 1 N u m b e r o f c a rd io v a s c u la r ris k fa c to rs Welmer et al. PLoS ONE 2013

Aims Incident limitation of APOE ɛ4 three physical functions Cardiovascular risk factors 6

Study Population Swedish National study on Aging and Care-Kungsholmen 7

Three outcomes 3363 952 with cardiovascular diseases 803 missing or with baseline limitation <5 seconds Analytical sample n =1401 94 missing or with baseline limitation <0.8 m/s 45 missing or with baseline limitation Cannot stand 69 missing APOE without using arms 8

Exposure APOE ε 4 Behavioural CRFs : Physical inactivity, current smoking, heavy alcohol consumption Cardiometabolic CRFs : Obesity, hypertension, high total cholesterol, diabetes Covariates : Sex, cognitive function (MMSE) Statistical analysis: Cox proportional hazards regression, with age as time-scale 9

APOE ε 4 and incident physical function limitation (n=1401) 4 H a z a rd R a tio s (9 5 % C I) 1 .5 7 2 1 .1 9 1 .1 4 1 0 .5 B a la n c e W a lk in g s p e e d C h a ir s ta n d lim ita tio n lim ita tio n lim ita tio n No. Incident cases N=211 N=153 N=180 Adjusted for sex, cognitive function, CRFs, and incident CVDs 10

Combined CRFs and APOE ε 4 and the risk of chair stand limitation 8 2 .5 3 H a z a rd R a tio s (9 5 % C I) 2 .5 6 4 1 .4 1 1 .3 5 1 .3 4 1 .0 1 2 1 0 .5 C R F s /  4 N /N Y /N N /Y Y /Y N /N Y /N N /Y Y /Y C a rd io m e ta b o lic C R F s B e h a vio u ra l C R F s 11 Adjusted for sex, cognitive function, and mutual CRFs

Behavioural CRFs and the risk of chair stand limitation 8 H a z a rd R a tio s (9 5 % C I) 2 .4 4 4 1 .8 8 1 .4 8 1 .2 9 1 .0 7 0 .8 5 2 1 0 .5 0 .2 5 n o  4  4 n o  4  4 n o  4  4 P h y s ic a l C u rre n t H e a vy a lco h o l in a c tiv ity s m o ke r c o n su m p tio n Adjusted for sex, cognitive function, and mutual CRFs

Conclusions • APOE ɛ 4 is associated with a greater risk of chair stand limitation among adults ≥60 years • Together behavioural CRFs and APOE ε 4 may heighten the risk of reduced muscle strength 13

Thank You! SNAC-K participants and data collectors Supervisors: Chengxuan Qiu, Anna-Karin Welmer, and Laura Fratiglioni Co-authors: Rui Wang, Debora Rizzuto Swedish Research Council Swedish Research Council for Health, Working Life and Welfare KID-Funding Eva & Oscar Ahréns Stiftelse Gun & Bertil Stohnes Stiftelse Stiftelsen Ragnhild och Einar Lundströms Minne Emerald.heiland@ki.se 14

3363 participants aged ≥60 years 952 with CVD at baseline 941 with limitation or missing in balance, walking speed, or chair stand Baseline at baseline survey 69 missing APOE gene (2001-2004) Flowchart Analytical sample 1401 participants 220 ≥78 years 1181<78 years 77 refused 15 refused 35 no contact 3 no contact 50 died 7 died 3 year follow-up 195 (2004-2007) 19 refused 1 no contact 16 died 6 year follow-up 1019 159 (2007-2010) 17 refused 7 refused 5 no contact 1 no contact 11 died 17 died 9 year follow-up 130 (2010-2013) 161-only 72 yrs

Guralnik et al. J Gerontol A 2000 Heiland et al. Age & Ageing 2016 Minneci J Am Geriatr Soc 2015 Perera J Gerontol A 2015 Physical Function Den Ouden et al. Exp Gerontol 2013 Newman et al. J Gerontol A 2003 Abellan van Kan et al. J Nutr Health Aging 2009 Kattainen et al. J Clin Epid 2004

CRFS definitions Behavioural CRFs Physical inactivity (never engaged in PA, engaged <2-3x/mo., or light and/or mod/intense 2-3x/mo.) vs. health-enhancing (light several times per wk) or fitness enhancing (mod/intense several times per wk) : questionnaire of activity in last 12 months (Rydwik Eur J Public Heal 2012) Heavy alcohol consumption vs. no occasional, light to moderate: based on a typical drinking day; >14 drinks per week for men or >7 for per week for women. One standard drink = 150ml (Breslow Am J Clin Nutr 2013) Current smoking vs. never or formerly: self-report Cardiometabolic CRFs Hypertension: ≥140/90mmHg or current use of anti-hypertensive agents(ATC codes; C02, C03, and C07-C09). (Perk Int J Beh Med 2012) Diabetes: according to self-reported history, records from the National Inpatient Registry, the use of hypoglycemic agents (ATC A10), or ≥6.5% glycated hemoglobin level. (Diabetes Care 2014) Total high cholesterol: ≥6.22mmol/L (non -fasting). (Cowie Diabetes Care 2006; Circulation 2002) Obesity: ≥30kg/m2. ( Obesity Research 1998)

Cardiovascular disease • Ascertainment of cardiovascular disease. Coronary heart disease, atrial fibrillation, heart failure, and cerebrovascular diseases were defined based on clinical examination, electrocardiogram, drug data, and Inpatient Register information (Calderón-Larrañaga J Gerontol A Biol Sci Med Sci 2016).

APOE Gene  Associated with brain disease (refs) – that increase the risk of disability  ε 4 allele known to increase risk of dementia  Associated with CVD (Haan et al. Curr Cardiovasc Risk Rep 2010)  Little known and discordant results on association with physical limitation  More longitudinal studies needed 19

APOE ε 4 and physical function (PF) limitation in longitudinal studies- inconsistent results PF studied PF associated with APOE Skoog et al. N=622 Grip strength Grip strength Front Aging 4 years follow-up Regular gait speed Neurosci 2016 Chair stand balance Alfred et al. N=23 916 Grip strength Cross-sectionally: chair AGE 2014 Years follow-up Get up and go/walking stand vary speed Longitudinally: walking Timed chair rise speed decline Balance ≥3s Melzer et al. N=1262 Gait speed 5 chair stands Gerontology 6 years follow-up 5 chair stands 2005 Verghese et N=627 Gait decline Only associated with gait al. 3 years follow-up Disability speed decline in men Gerontology 2013

Buchman Alzheimer N=876 Time and number of steps to Motor decline, mainly Dis Assoc Disord 10 years walk 8ft and turn; time to stand due to muscle strength 2009 on each leg an then on their toes for 10secs; number of steps off line when walking; number of pegs that could be placed (Purdue pegboard) in 30 secs

Is physical function heritable? • Twin studies • Suggested that there is a high heredity component in connection with chair stand and walking speed, but not balance (Carmelli et al. J Gerontol 2000) • Genetic factors accounted for 46% of the variance in repeated chair stands (Carmelli et al. J Gerontol 2000) • Offspring of parents with genes for good physical funcion are more likely to have better results on this association

Thank You! SNAC-K participants and data collectors Supervisors: Chengxuan Qiu, Anna-Karin Welmer, and Laura Fratiglioni Co-authors: Rui Wang, Debora Rizzuto Swedish Research Council Swedish Research Council for Health, Working Life and Welfare KID-Funding Eva & Oscar Ahréns Stiftelse Gun & Bertil Stohnes Stiftelse Stiftelsen Ragnhild och Einar Lundströms Minne Emerald.heiland@ki.se 23