The EPI/NPAM Spring 2014 Scientific Sessions, Hilton San Francisco Union Square, San Francisco, CA Northwestern Mar. 18-21, 2014 University Feinberg School of Medicine Long-term Blood Pressure Variability throughout Young Adulthood and Cognitive Function in Midlife; CARDIA study Yuichiro Yano, MD, 1 Hongyan Ning, MD, MS, 1 Norrina Allen, PhD, 1 MPH, Jared P. Reis, PhD, 2 Lenore J. Launer, PhD, 3 Kiang Liu, PhD, 1 Kristine Yaffe, MD, 4 Philip Greenland, MD, 1 and Donald Lloyd-Jones MD, ScM 1 1. Department of Preventive Medicine, Northwestern University Feinberg School of Medicine 2. Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute 3. Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging 4. Department of Psychiatry, University of California, San Francisco, CA, US
Presenter Disclosure Information Elements Yuichiro Yano, MD Department of Preventive Medicine, Northwestern University Feinberg School of Medicine FINANCIAL DISCLOSURE: Manpei Suzuki International Prize for Diabetes Research
BP variability (BPV) Short-term BPV (e.g., beat-to-beat and within 24-hours) Long-term BPV (e.g., day-by-day, visit-to-visit (monthly, yearly) BPV). Parati G. Nat Rev Cardiol. 2013;10(3):143.
Background The association of long-term (1-8 years) BPV with cognitive dysfunction has been recently reported among elderly and highrisk populations. 1-3 The association of long-term BPV with cognitive function in young adults remains uncertain 1. Sabayan et al., BMJ. 2013;347:f4600. 2. Alpérovitch et al.,alzheimers Dement. 2013. pii: S1552-5260(13)02474-6. 3. Nagai M, et al. J Hypertens. 2012;30(8):1556-1563.
Objectives We sought to determine whether: Long-term BPV throughout young adulthood (25 years) is associated with cognitive function in midlife Diverse domains of cognition (i.e., psychomotor speed, verbal memory, and executive function) are differentially associated with long-term BPV
Longitudinal study of lifestyle and the evolution of CVD risk factors in young adults 5,115 black and white men and women of varying educational attainment Aged 18 30 at baseline (1985 1986) Four study centers: Chicago IL, Birmingham AL, Minneapolis MN, Oakland CA Follow-up examinations at years 2, 5, 7, 10, 15, 20, 25
BPV measurements Average real variability (ARV) ( Δ1 + Δ2 + Δ3 + Δ4 + Δ5 + Δ6 + Δ7 ) / 7 SBP, mmhg 130 120 110 100 Mean SBP across 8 visits SBP M1 Δ1 M2 M3 Δ2 Δ3 Minimum SBP M4 Δ4 M5 Δ5 Maximum SBP M6 Δ6 M7 Cumulative exposure of SBP Δ7 Standard deviation (+coefficient of variation) Y 0 Y 2 Y 5 Y 7 Y 10 Y 15 Y 20 Y 25 Cumulative exposure of BP; (M1 2year+ M2 3year + M3 2year + M4 3year + M5 5year + M6 5year + M7 5year)
Outcomes Cognitive function was assessed (n=2,326) at Y 25 with Digit Symbol Substitution Test (DSST, psychomotor speed test), Rey Auditory Verbal Learning Test (RAVLT, verbal memory test) Modified Stroop test (executive function test)
Baseline characteristics of participants (n=2,326) Age, years 25.3+3.5 Men, % 43.3 Blacks, % 40.2 Education, years 14.3+2.2 Body mass index, kg/m 2 24.4+4.7 Current smoker, % 5.7 Current drinker, % 61.5 Physical activity, exercise units 424.7+296.9 Antihypertensive medication, % 1.9 SBP, mmhg 109.8+10.8 DBP, mmhg 68.5+9.2 Fasting glucose, mg/dl 82.1+11.4 Total cholesterol, mg/dl 177.7+32.8 High-density lipoprotein, mg/dl 53.3+12.6 Data are expressed as the means ± SD or percentage.
Age, sex, and race-adjusted correlation of SD BP and ARV BP with the demographics and clinical characteristics (n=2,326) SD SBP, mmhg SD DBP, mmhg ARV SBP, mmhg Demographics at Y 0 Education, years -.10 *** -.10 *** -.13 *** -.11 *** Clinical characteristics at Y 25 Body mass index, kg/m 2.17 ***.21 ***.12 ***.10 *** Physical activity, -.07 ** -.06 ** -.06 ** -.04 ARV DBP, mmhg exercise units Fasting glucose, mg/dl.11 ***.10 ***.13 ***.06 ** Total cholesterol, mg/dl.04.03 -.01.003 High-density lipoprotein, mg/dl -.09 *** -.10 *** -.07 *** -.05 * Pearson s correlation coefficients adjusted by age, sex, and race are shown. SD and ARV were calculated by BP measures across 8 visits (Y 0-25 ). * P<.05; ** P <.01; *** P<.001.
Mean (95% CIs) scores of cognitive function test by deciles of ARV BP Digit Symbol Substitution Test (symbols) ARV SBP P for trend ARV DBP P=.0004 for trend Lower score means lower Psychomotor speed Rey Auditory Verbal Learning Test (words) P=.04 P=.02 Lower score means lower verbal memory Stroop test (sec + errors) P=.03 P=.41 Higher score means lower executive function Deciles of ARV SBP Deciles of ARV DBP Adjusted for age, sex, race, education, and study site.
Mean (95% CIs) scores of cognitive function test by deciles of SD BP Digit Symbol Substitution Test (symbols) SD SBP P=.01 for trend SD DBP P=.003 for trend Lower score means lower Psychomotor speed Rey Auditory Verbal Learning Test (words) P=.08 P=.003 Lower score means lower verbal memory Stroop test (sec + errors) P=.23 P=.18 Higher score means lower executive function Deciles of SD SBP Deciles of SD DBP Adjusted for age, sex, race, education, and study site
Linear regression models to examine the associations of BPV with cognitive function (n=2,326) Model 1 (Unadjusted) P β (SE) value Digit Symbol Substitution Test (symbols); Model 2 Model 3 Model 4 β (SE) P value β (SE) P value β (SE) P value Lower score means lower Psychomotor speed test SD SBP SD DBP -.047 (.005) -.068 (.007) -.022 (.004) -.034 (.006) -.022 (.006) -.030 (.008) <.001 -.017 (.005) -.029 (.007) ARV SBP -.064 (.006) -.033 (.005) -.026 (.006) -.025 (.006) ARV DBP -.067 (.007) -.034 (.006) -.028 (.007) -.029 (.007) Rey Auditory Verbal Learning Test (words): Lower score means lower verbal memory test <.01 SD SBP SD DBP -.029 (.005) -.056 (.007) -.013 (.005) -.024 (.007) <.01 <0.001 -.010 (.007) -.018 (.008) ARV SBP -.044 (.006) -.021 (.005) -.016 (.006) ARV DBP -.055 (.007) -.026 (.007) <0.001 -.020 (.007) β means standardized regression coefficient. As adjustment factors, Model 2 includes age at baseline, sex, race, education, and study center.13 <.05 <.05 <.01 -.008 (.005) -.019 (.007) -.016 (.006) -.021 (.007).12 <.01 <.05 <.01 Model 3 includes model 2+ clinical characteristics at Y 25 (BMI, smoking, alcohol, physical activity, fasting glucose, total cholesterol/hdl, use of antihypertensive drugs, incidence of stroke) + BP (Y 0 ) and change of BP (Y 25 -Y 0 ) Model 4 included model 2+ clinical characteristics at Y 25 + cumulative exposure of BP (Y 0-25 ).
Linear regression models to examine the associations of BPV with cognitive function (n=2,326) Model 1 (Unadjusted) Model 2 Model 3 Model 4 β (SE) P value β (SE) P value β (SE) P value β (SE) P value Stroop test (sec + errors): Higher score means lower executive function test SD SBP.042 (.005) SD DBP.051 (.007).013 (.005).013 (.007) <.01 0.053.002 (.007).004 (.008).73.61.004 (.005).004 (.007).41.60 ARV SBP.045 (.006) ARV DBP.043 (.007).015 (.006).011 (.007) <.01 0.12.004 (.006).004 (.007).52.54.004 (.006).004 (.007).50.53 β means standardized regression coefficient, and R 2 means a measure for the model prediction. As adjustment factors, Model 2 includes age at baseline, sex, race, education, and study center Model 3 includes model 2+ clinical characteristics at Y 25 (BMI, smoking, alcohol, physical activity, fasting glucose, total cholesterol/hdl, use of antihypertensive drugs, incidence of stroke) + BP (Y 0 ) and change of BP (Y 25 -Y 0 ) Model 4 included model 2+ clinical characteristics at Y 25 + cumulative exposure of BP (Y 0-25 ).
Strengths and Limitations Strengths CARDIA cohort, a well phenotyped longitudinal cohort with high-quality measures of BP and cognitive function Limitations We could not assess change in cognitive function over time A number of people from the original cohort were excluded in the present analysis (55%)
Summary and Conclusions Higher long-term BPV throughout young adulthood (25 years 50 years) is associated with lower function of psychomotor speed (i.e., DSST) and verbal memory (i.e., RAVLT) in midlife. These data suggest the testable hypothesis that reduction of BPV throughout the young adults could lead to improvement in cognitive function in midlife
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Correlation of SD BP with CV BP and MMD BP (n=2,326) SD SBP, mmhg SD DBP, mmhg CV SBP, mmhg.98 ***.61 *** CV DBP, mmhg.54 ***.96 *** MMD SBP, mmhg.98 ***.63 *** MMD DBP, mmhg.63 ***.97 *** Pearson s correlation coefficients are shown. SBP indicates systolic blood pressure; DBP, diastolic blood pressure; SD; standard deviation, CV; coefficient of variation, MMD; maximum and minimum BP difference. *** P<0.001.
Age, sex, and race-adjusted correlation of SD BP and ARV BP with the demographics and clinical characteristics (n=2,326) SD SBP, mmhg SD DBP, mmhg ARV SBP, mmhg ARV DBP, mmhg Demographics at Y 0 Education, years -.10 *** -.10 *** -.13 *** -.11 *** Demographics at Y 25 Body mass index, kg/m 2.17 ***.21 ***.12 ***.10 *** Physical activity, exercise units -.07 ** -.06 ** -.06 ** -.04 Fasting glucose, mg/dl.11 ***.10 ***.13 ***.06 ** Total cholesterol, mg/dl.04.03 -.01.003 High-density lipoprotein, mg/dl -.09 *** -.10 *** -.07 *** -.05 * BP parameters Change of SBP (Y 25 -Y 0 ), mmhg.59 ***.36 ***.22 ***.12 *** Change of DBP (Y 25 -Y 0 ), mmhg.42 ***.47 ***.15 ***.17 *** Average SBP (Y 0-25 ), mmhg.48 ***.41 ***.43 ***.30 *** Average DBP (Y 0-25 ), mmhg.40 ***.28 ***.38 ***.19 *** Cumulative exposure of.52 ***.44 ***.44 ***.31 *** SBP (Y 0-25 ), mmhg Cumulative exposure of DBP (Y 0-25 ), mmhg.44 ***.35 ***.38 ***.22 *** Pearson s correlation coefficients adjusted by age, sex, and race are shown. SD and ARV were calculated by BP measures across 8 visits (Y 0-25 ). * P<.05; ** P <.01; *** P<.001.
Mean (95% CIs) scores of cognitive function test with adjustment for age, sex, race, education, and study site in deciles of ARV BP Digit Symbol Substitution Test (symbols) P for trend P=.0004 for trend Lower score means lower Psychomotor speed test Rey Auditory Verbal Learning Test (words) P=.04 P=.02 Lower score means lower verbal memory test Stroop test (sec + errors) P=.03 P=.41 Higher score means lower executive function test Deciles of ARV SBP Deciles of ARV DBP The range of ARV divided by deciles. 1 st 2 nd 3 rd 4 th 5 th 6 th 7 th 8 th 9 th 10 th Mean+SD ARV SBP, 1.2-4.4 4.4-5.3 5.3-6.0 6.0-6.7 6.7-7.4 7.4-8.2 8.2-9.1 9.1-10.3 10.3-12.4 12.4-48.4 8.0+3.5 mmhg (n=232) (n=233) (n=233) (n=228) (n=235) (n=235) (n=228) (n=235) (n=234) (n=233) ARV DBP, mmhg 1.3-4.0 (n=232) 4.0-4.8 (n=233) 4.8-5.5 (n=233) 5.5-6.1 (n=235) 6.1-6.9 (n=219) 6.9-7.4 (n=244) 7.4-8.3 (n=231) 8.3-9.3 (n=233) 9.3-11.0 (n=234) 11.0-22.3 (n=232) 7.2+2.8