Higher Adiposity Is Associated With Slower Cognitive Decline in Hypertensive Patients: Secondary Analysis of the China Stroke Primary Prevention Trial

Jun Zhang, Genfu Tang, Haiqun Xie, Binyan Wang, Mingli He, Jia Fu, Xiuli Shi, Chengguo Zhang, Yong Huo, Xiping Xu, Kai Wang, Jun Zhang, Genfu Tang, Haiqun Xie, Binyan Wang, Mingli He, Jia Fu, Xiuli Shi, Chengguo Zhang, Yong Huo, Xiping Xu, Kai Wang

Abstract

Background: Obesity is a risk factor for many diseases. However, the potential association between adiposity and cognitive decline in hypertensive patients is inconclusive. We performed a secondary data analysis of the CSPPT (China Stroke Primary Prevention Trial) to examine whether adiposity is correlated with longitudinal cognitive performance in hypertensive adults.

Methods and results: The analysis included 16 791 patients in the CSPPT who received at least 2 cognitive assessments by the Mini-Mental State Examination (MMSE) during the follow-up (median, 4.5 years; interquartile range, 4.2-4.8 years). Outcomes included changes in MMSE scores and cognitive impairment (defined as MMSE score less than education-specific cutoff point). A marked reduction in MMSE scores at the final (compared with at the 1-year) follow-up was apparent in both men (n=4838; mean [SD] score, 0.41 [3.62]) and women (n=7190; mean [SD] score, 1.07 [4.61]; both P<0.001). Analysis using a mixed-effects model revealed an association between higher body mass index with less MMSE decline, even after controlling for demographics and comorbidities (men, β=0.0134 [SE, 0.0036]; women, β=0.0133 [SE, 0.0034]; both P<0.001). A total of 1037 men (15.3%) and 3317 women (33.1%) developed cognitive impairment. In multivariable Cox regression analyses, being obese in men (11.3% versus 18.0%; hazard ratio, 0.75; 95% confidence interval, 0.60-0.94) and women (30.1% versus 36.5%; hazard ratio, 0.82; 95% confidence interval, 0.74-0.91) was a protective factor against cognitive impairment compared with normal body mass index.

Conclusions: Higher adiposity is independently associated with slower cognitive decline in Chinese hypertensive adults.

Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00794885 CSPPT.

Keywords: adiposity; body mass index; cognitive decline; hypertension; waist circumference.

© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Figures

Figure 1
Figure 1
The study flow chart for post hoc cognition analysis of the CSPPT (China Stroke Primary Prevention Trial). BMI indicates body mass index; and MMSE, Mini‐Mental State Examination.
Figure 2
Figure 2
Unadjusted mean change in total Mini‐Mental State Examination (MMSE) score by body mass index (BMI) categories at baseline. Changes of MMSE scores at the 3‐year follow‐up visit and final follow‐up visit vs the 1‐year follow‐up visit are presented in men (A) and women (B). A, After adjusting for covariates, the changes in total MMSE score between all other BMI groups and normal‐weight group are not statistically significant at 3‐year follow‐up visit vs 1‐year follow‐up visit; the change in total MMSE score between obesity group and normal‐weight group is P=0.004 at final follow‐up visit vs 1‐year follow‐up visit. B, After adjusting for covariates, the change in total MMSE score between obesity group and normal‐weight group is P=0.004 at 3‐year follow‐up visit vs 1‐year follow‐up visit; the changes in total MMSE score between overweight group and normal‐weight group and between obesity group and normal‐weight group are P=0.027 and P<0.027, respectively, at final follow‐up visit vs 1‐year follow‐up visit. Error bars indicate 95% confidence intervals. Numbers outside parentheses represent number of participants with available data at each follow‐up visit, and numbers in parentheses represent number of participants with available data on the changes of MMSE between 3‐year follow‐up (or final follow‐up) and 1‐year follow‐up.
Figure 3
Figure 3
Relationship between body mass index (BMI) at baseline and risk of cognitive impairment by penalized splines. The relative risk of cognitive impairment in association with BMI is shown in men (A) and women (B). Solid lines represent the log hazard ratios for BMI as a continuous variable, and dashed lines represent the 95% confidence intervals. The graphs are truncated at the 1st and 99th percentiles of BMI. Analyses are adjusted for study center, age, education, smoking status, alcohol drinking, marital status, living conditions, physical activity, Patient Health Questionnaire‐9 scores, systolic blood pressure (SBP) at baseline, mean SBP during the follow‐up, estimated glomerular filtration rate, new stroke, diabetes mellitus at baseline, new diabetes mellitus during the follow‐up, and treatment allocation.

References

    1. WHO . Obesity and overweight fact sheet number 311. Updated January, 2015. Geneva: World Health Organization; 2015. . Accessed March 23, 2015.
    1. Prince M, Wilmo A, Guerchet M, Ali GC, Wu YT, Prina M. World Alzheimer Report 2015: The Global Impact of Dementia. London, England: Alzheimer's Disease International; 2015.
    1. Whitmer RA, Gunderson EP, Barrett‐Connor E, Quesenberry CP Jr, Yaffe K. Obesity in middle age and future risk of dementia: a 27 year longitudinal population based study. BMJ. 2005;330:1360.
    1. Loef M, Walach H. Midlife obesity and dementia: meta‐analysis and adjusted forecast of dementia prevalence in the United States and China. Obesity (Silver Spring). 2013;21:E51–E55.
    1. Cournot M, Marquie JC, Ansiau D, Martinaud C, Fonds H, Ferrieres J, Ruidavets JB. Relation between body mass index and cognitive function in healthy middle‐aged men and women. Neurology. 2006;67:1208–1214.
    1. Dahl A, Hassing LB, Fransson E, Berg S, Gatz M, Reynolds CA, Pedersen NL. Being overweight in midlife is associated with lower cognitive ability and steeper cognitive decline in late life. J Gerontol A Biol Sci Med Sci. 2010;65:57–62.
    1. Uretsky S, Messerli FH, Bangalore S, Champion A, Cooper‐Dehoff RM, Zhou Q, Pepine CJ. Obesity paradox in patients with hypertension and coronary artery disease. Am J Med. 2007;120:863–870.
    1. Vemmos K, Ntaios G, Spengos K, Savvari P, Vemmou A, Pappa T, Manios E, Georgiopoulos G, Alevizaki M. Association between obesity and mortality after acute first‐ever stroke: the obesity‐stroke paradox. Stroke. 2011;42:30–36.
    1. Khalid U, Ather S, Bavishi C, Chan W, Loehr LR, Wruck LM, Rosamond WD, Chang PP, Coresh J, Virani SS, Nambi V, Bozkurt B, Ballantyne CM, Deswal A. Pre‐morbid body mass index and mortality after incident heart failure: the ARIC Study. J Am Coll Cardiol. 2014;64:2743–2749.
    1. Carnethon MR, De Chavez PJ, Biggs ML, Lewis CE, Pankow JS, Bertoni AG, Golden SH, Liu K, Mukamal KJ, Campbell‐Jenkins B, Dyer AR. Association of weight status with mortality in adults with incident diabetes. JAMA. 2012;308:581–590.
    1. Vashistha T, Mehrotra R, Park J, Streja E, Dukkipati R, Nissenson AR, Ma JZ, Kovesdy CP, Kalantar‐Zadeh K. Effect of age and dialysis vintage on obesity paradox in long‐term hemodialysis patients. Am J Kidney Dis. 2014;63:612–622.
    1. Hakimi AA, Furberg H, Zabor EC, Jacobsen A, Schultz N, Ciriello G, Mikklineni N, Fiegoli B, Kim PH, Voss MH, Shen H, Laird PW, Sander C, Reuter VE, Motzer RJ, Hsieh JJ, Russo P. An epidemiologic and genomic investigation into the obesity paradox in renal cell carcinoma. J Natl Cancer Inst. 2013;105:1862–1870.
    1. Nie W, Zhang Y, Jee SH, Jung KJ, Li B, Xiu Q. Obesity survival paradox in pneumonia: a meta‐analysis. BMC Med. 2014;12:61.
    1. Wang J, Zhang L, Wang F, Liu L, Wang H; China National Survey of Chronic Kidney Disease Working Group . Prevalence, awareness, treatment, and control of hypertension in China: results from a national survey. Am J Hypertens. 2014;27:1355–1361.
    1. Yang W, Li JP, Zhang Y, Fan FF, Xu XP, Wang BY, Xu X, Qin XH, Xing HX, Tang GF, Zhou ZY, Gu DF, Zhao D, Huo Y. Association between body mass index and all‐cause mortality in hypertensive adults: results from the China Stroke Primary Prevention Trial (CSPPT). Nutrients. 2016;8:E384. DOI: 10.3390/nu8060384.
    1. Huo Y, Li J, Qin X, Huang Y, Wang X, Gottesman RF, Tang G, Wang B, Chen D, He M, Fu J, Cai Y, Shi X, Zhang Y, Cui Y, Sun N, Li X, Cheng X, Wang J, Yang X, Yang T, Xiao C, Zhao G, Dong Q, Zhu D, Wang X, Ge J, Zhao L, Hu D, Liu L, Hou FF; CSPPT Investigators . Efficacy of folic acid therapy in primary prevention of stroke among adults with hypertension in China: the CSPPT randomized clinical trial. JAMA. 2015;313:1325–1335.
    1. Zhou BF; Cooperative Meta‐Analysis Group of the Working Group on Obesity in C hina. Predictive values of body mass index and waist circumference for risk factors of certain related diseases in Chinese adults: study on optimal cut‐off points of body mass index and waist circumference in Chinese adults. Biomed Environ Sci. 2002;15:83–96.
    1. Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, Fruchart JC, James WP, Loria CM, Smith SC Jr; International Diabetes Federation Task Force on Epidemiology and Prevention; Hational Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; International Association for the Study of O besity. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation. 2009;120:1640–1645.
    1. Folstein MF, Folstein SE, McHugh PR. “Mini‐mental state:” a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12:189–198.
    1. Zhang MY, Katzman R, Salmon D, Jin H, Cai GJ, Wang ZY, Qu GY, Grant I, Yu E, Levy P, Klauber MR, Liu WT. The prevalence of dementia and Alzheimer's disease in Shanghai, China: impact of age, gender, and education. Ann Neurol. 1990;27:428–437.
    1. Tzourio C, Anderson C, Chapman N, Woodward M, Neal B, MacMahon S, Chalmers J; PROGRESS Collaborative Group . Effects of blood pressure lowering with perindopril and indapamide therapy on dementia and cognitive decline in patients with cerebrovascular disease. Arch Intern Med. 2003;163:1069–1075.
    1. Spitzer RL, Kroenke K, Williams JB. Validation and utility of a self‐report version of PRIME‐MD: the PHQ primary care study: Primary Care Evaluation of Mental Disorders: Patient Health Questionnaire. JAMA. 1999;282:1737–1744.
    1. Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF III, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T, Coresh J. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150:604–612.
    1. Jackson AS, Stanforth PR, Gagnon J, Rankinen T, Leon AS, Rao DC, Skinner JS, Bouchard C, Wilmore JH. The effect of sex, age and race on estimating percentage body fat from body mass index: the Heritage Family Study. Int J Obes Relat Metab Disord. 2002;26:789–796.
    1. Snijder MB, van Dam RM, Visser M, Seidell JC. What aspects of body fat are particularly hazardous and how do we measure them? Int J Epidemiol. 2006;35:83–92.
    1. Whitmer RA, Gustafson DR, Barrett‐Connor E, Haan MN, Gunderson EP, Yaffe K. Central obesity and increased risk of dementia more than three decades later. Neurology. 2008;71:1057–1064.
    1. Sakakura K, Hoshide S, Ishikawa J, Momomura S, Kawakami M, Shimada K, Kario K. Association of body mass index with cognitive function in elderly hypertensive Japanese. Am J Hypertens. 2008;21:627–632.
    1. Hughes TF, Borenstein AR, Schofield E, Wu Y, Larson EB. Association between late‐life body mass index and dementia: the Kame Project. Neurology. 2009;72:1741–1746.
    1. Luchsinger JA, Patel B, Tang MX, Schupf N, Mayeux R. Measures of adiposity and dementia risk in elderly persons. Arch Neurol. 2007;64:392–398.
    1. Flegal KM, Kit BK, Orpana H, Graubard BI. Association of all‐cause mortality with overweight and obesity using standard body mass index categories: a systematic review and meta‐analysis. JAMA. 2013;309:71–82.
    1. Angeras O, Albertsson P, Karason K, Ramunddal T, Matejka G, James S, Lagerqvist B, Rosengren A, Omerovic E. Evidence for obesity paradox in patients with acute coronary syndromes: a report from the Swedish Coronary Angiography and Angioplasty Registry. Eur Heart J. 2013;34:345–353.
    1. Qizilbash N, Gregson J, Johnson ME, Pearce N, Douglas I, Wing K, Evans SJ, Pocock SJ. BMI and risk of dementia in two million people over two decades: a retrospective cohort study. Lancet Diabetes Endocrinol. 2015;3:431–436.
    1. Johnson DK, Wilkins CH, Morris JC. Accelerated weight loss may precede diagnosis in Alzheimer disease. Arch Neurol. 2006;63:1312–1317.
    1. Knopman DS, Edland SD, Cha RH, Petersen RC, Rocca WA. Incident dementia in women is preceded by weight loss by at least a decade. Neurology. 2007;69:739–746.
    1. Fitzpatrick AL, Kuller LH, Lopez OL, Diehr P, O'Meara ES, Longstreth WT Jr, Luchsinger JA. Midlife and late‐life obesity and the risk of dementia: cardiovascular health study. Arch Neurol. 2009;66:336–342.
    1. Sturman MT, de Leon CF, Bienias JL, Morris MC, Wilson RS, Evans DA. Body mass index and cognitive decline in a biracial community population. Neurology. 2008;70:360–367.
    1. Patel BN, Pang D, Stern Y, Silverman W, Kline JK, Mayeux R, Schupf N. Obesity enhances verbal memory in postmenopausal women with Down syndrome. Neurobiol Aging. 2004;25:159–166.
    1. Nishihara R, VanderWeele TJ, Shibuya K, Mittleman MA, Wang M, Field AE, Giovannucci E, Lochhead P, Ogino S. Molecular pathological epidemiology gives clues to paradoxical findings. Eur J Epidemiol. 2015;30:1129–1135.
    1. Lieb W, Beiser AS, Vasan RS, Tan ZS, Au R, Harris TB, Roubenoff R, Auerbach S, DeCarli C, Wolf PA, Seshadri S. Association of plasma leptin levels with incident Alzheimer disease and MRI measures of brain aging. JAMA. 2009;302:2565–2572.
    1. Okereke O, Kang JH, Ma J, Hankinson SE, Pollak MN, Grodstein F. Plasma IGF‐I levels and cognitive performance in older women. Neurobiol Aging. 2007;28:135–142.
    1. Driscoll I, Gaussoin SA, Wassertheil‐Smoller S, Limacher M, Casanova R, Yaffe K, Resnick SM, Espeland MA. Obesity and structural brain integrity in older women: the Women's Health Initiative Magnetic Resonance Imaging Study. J Gerontol A Biol Sci Med Sci. 2016;71:1216–1222.
    1. Golan R, Shelef I, Rudich A, Gepner Y, Shemesh E, Chassidim Y, Harman‐Boehm I, Henkin Y, Schwarzfuchs D, Ben Avraham S, Witkow S, Liberty IF, Tangi‐Rosental O, Sarusi B, Stampfer MJ, Shai I. Abdominal superficial subcutaneous fat: a putative distinct protective fat subdepot in type 2 diabetes. Diabetes Care. 2012;35:640–647.
    1. Fox CS, Massaro JM, Hoffmann U, Pou KM, Maurovich‐Horvat P, Liu CY, Vasan RS, Murabito JM, Meigs JB, Cupples LA, D'Agostino RB Sr, O'Donnell CJ. Abdominal visceral and subcutaneous adipose tissue compartments: association with metabolic risk factors in the Framingham Heart Study. Circulation. 2007;116:39–48.
    1. Esmaillzadeh A, Mirmiran P, Moeini SH, Azizi F. Larger hip circumference independently contributed to reduced metabolic risks in Tehranian adult women. Int J Cardiol. 2006;108:338–345.
    1. Hainer V, Aldhoon‐Hainerova I. Obesity paradox does exist. Diabetes Care. 2013;36(suppl 2):S276–S281.
    1. Lajous M, Banack HR, Kaufman JS, Hernan MA. Should patients with chronic disease be told to gain weight? The obesity paradox and selection bias. Am J Med. 2015;128:334–336.
    1. Xu G, Meyer JS, Huang Y, Du F, Chowdhury M, Quach M. Adapting mini‐mental state examination for dementia screening among illiterate or minimally educated elderly Chinese. Int J Geriatr Psychiatry. 2003;18:609–616.
    1. Cukierman‐Yaffe T, Anderson C, Teo K, Gao P, Gerstein HC, Yusuf S; ONTARGET/TRANSCEND Investigators . Dysglycemia and cognitive dysfunction and ill health in people with high Cv risk: results from the ONTARGET/TRANSCEND studies. J Clin Endocrinol Metab. 2015;100:2682–2689.

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