Effects of Higher Normal Blood Pressure on Brain Are Detectable before Middle-Age and Differ by Sex
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design and Participants
2.2. Blood Pressure
2.3. Image Acquisition
2.4. Segmentation and Image Analysis
2.5. Covariates
2.6. Statistical Analyses
3. Results
3.1. Age and Brain Volumes
3.2. BP and Brain Volumes
BMI Effects
3.3. Antihypertensive Medication Effects
3.4. Vascular Stiffness Effects
3.5. Effects within the Normal BP Range
4. Discussion
Implications for Health Policy and Clinical Practice
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Appendix A
Selected vs. Non-Selected | ||||
---|---|---|---|---|
Measures | Whole Sample | Not Selected | Selected | T/chi-sq Test (p-Value) |
Age, year (SD) | 56.53 (8.10) | 56.43 (8.09) | 56.54 (8.10) | −2.81 (0.005) |
SBP, mmHg (SD) | 139.74 (19.70) | 139.97 (20.35) | 139.73 (19.68) | 1.20 (0.230) |
DBP, mmHg (SD) | 82.21 (10.70) | 82.66 (11.19) | 82.19 (10.69) | 4.36 (0.000) |
BMI, kg/m2 (SD) | 27.43 (4.80) | 27.77 (5.21) | 27.40 (4.76) | 14.40 (0.000) |
Cholesterol, mmol/L | 5.69 (1.14) | 5.70 (1.16) | 5.69 (1.14) | 1.14 (0.255) |
HDL mmol/L | 1.45 (0.38) | 1.43 (0.38) | 1.45 (0.38) | −7.35 (0.000) |
Sex, n (Male%) | 229,134 (50.00%) | 20,295 (44.56%) | 208,839 (45.70%) | 21.63 (0.000) |
Smoking, n (%) | 301,690 (59.69%) | 26,604 (59.16%) | 272,187 (59.86%) | 8.41 (0.004) |
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Measures | Whole Sample | Men | Women | T/chi-sq Test (p-Value) |
---|---|---|---|---|
Age, year (SD) | 54.88 (7.47) | 55.58 (7.57) | 54.26 (7.33) | 16.89 (0.000) |
SBP, mmHg (SD) | 134.90 (17.71) | 138.80 (16.46) | 131.39 (18.06) | 40.85 (0.000) |
DBP, mmHg (SD) | 81.37 (9.90) | 83.56 (9.64) | 79.41 (9.72) | 40.79 (0.000) |
MAP, mmHg (SD) | 99.21 (11.66) | 101.97 (11.07) | 96.73 (11.63) | 43.91 (0.000) |
PP, mmHg (SD) | 53.52 (12.34) | 55.24 (11.55) | 51.98 (12.80) | 25.45 (0.000) |
GM, mm3 (SD) | 665,373.52 (59,587.27) | 699,375.78 (53,696.16) | 634,797.84 (46651.03) | 121.62 (0.000) |
WM volume, mm3 (SD) | 478,100.24 (57,260.97) | 508,577.33 (53,010.15) | 450,694.48 (45979.19) | 110.50 (0.000) |
Left HC volume, mm3 (SD) | 3673.24 (395.67) | 3689.78 (389.09) | 3649.69 (403.70) | 9.45 (0.000) |
Right HC volume, mm3 (SD) | 3792.48 (402.87) | 3807.18 (394.35) | 3771.55 (413.81) | 8.23 (0.000) |
WMLs volume, mm3 (SD) | 7.40 (0.68) | 7.54 (0.67) | 7.27 (0.66) | 37.42 (0.000) |
ICV, mm3 (SD) | 1,548,411.25 (152,104.52) | 1,542,329.21 (149,601.04) | 1,557,069.86 (155,193.42) | −9.04 (0.000) |
BMI, kg/m2 (SD) | 26.56 (4.22) | 27.12 (3.76) | 26.07 (4.54) | 24.16 (0.000) |
Cholesterol, mmol/L, (SD) | 5.73 (1.08) | 5.59 (1.08) | 5.85 (1.07) | −22.50 (0.000) |
HDL mmol/L, (SD) | 1.48 (0.38) | 1.31 (0.30) | 1.63 (0.37) | −91.50 (0.000) |
Hypertension, n (%) | 14,961 (41.26%) | 8421 (49.05%) | 6540 (34.26%) | 815.84 (0.000) |
Antihypertensive medication, n (%) | 2645 (7.29%) | 1334 (7.77%) | 1311 (6.87%) | 10.78 (0.001) |
Diabetes mellitus, n (%) | 950 (2.62%) | 473 (2.22%) | 477 (3.19%) | 31.87 (0.000) |
Ever smoked, n (%) | 14,149 (39.02%) | 7979 (37.46%) | 6170 (41.24%) | 52.58 (0.000) |
Higher Education, n (%) | 17,525 (48.33%) | 10,692 (50.20%) | 6833 (45.67%) | 71.95 (0.000) |
Gray Matter Volume (mm3) | White Matter Volume (mm3) | Left Hippocampus Volume (mm3) | Right Hippocampus Volume (mm3) | White Matter Lesions Volume (mm3) | ||||||
---|---|---|---|---|---|---|---|---|---|---|
Beta (SE) | Beta (SE) | Beta (SE) | Beta (SE) | Beta (SE) | ||||||
Participants Aged ≤ 45 Years | ||||||||||
Men, n = 2220 | Women, n = 2867 | Men, n = 2220 | Women, n = 2867 | Men, n = 2220 | Women, n = 2867 | Men, n = 2220 | Women, n = 2867 | Men, n = 2220 | Women, n = 2867 | |
MAP | −268.346 *** (62.485) | −246.073 *** (47.730) | 7.341 (63.676) | −110.942 ** (47.813) | 0.850 (0.669) | −1.158 ** (0.519) | 0.586 (0.677) | −1.061 ** (0.516) | 0.003 *** (0.001) | 0.003 *** (0.001) |
SBP | −179.415 *** (47.880) | −172.891 *** (35.186) | −8.685 (48.744) | −85.832 ** (35.229) | 0.773 (0.512) | −0.628 (0.383) | 0.823 (0.518) | −0.502 (0.381) | 0.002 *** (0.001) | 0.002 *** (0.001) |
DBP | −285.528 *** (66.856) | −258.127 *** (52.955) | 21.088 (68.126) | −107.449 ** (53.033) | 0.704 (0.716) | −1.426 ** (0.576) | 0.203 (0.725) | −1.389 ** (0.572) | 0.003 *** (0.001) | 0.003 *** (0.001) |
Participants Aged between 46–55 years | ||||||||||
Men, n = 5699 | Women, n = 7456 | Men, n = 5699 | Women, n = 7456 | Men, n = 5699 | Women, n = 7456 | Men, n = 5699 | Women, n = 7456 | Men, n = 5699 | Women, n = 7456 | |
MAP | −212.574 *** (38.583) | −228.546 *** (26.449) | −115.987 *** (37.605) | −60.878 ** (27.318) | −0.453 (0.394) | −0.236 (0.284) | −0.291 (0.399) | −0.368 (0.281) | 0.006 *** (0.001) | 0.007 *** (0.0005) |
SBP | −133.847 *** (27.786) | −151.197 *** (18.091) | −83.331 *** (27.064) | −8.702 (18.685) | −0.067 (0.284) | −0.062 (0.194) | −0.003 (0.287) | −0.086 (0.192) | 0.004 *** (0.0004) | 0.005 *** (0.0003) |
DBP | −237.579 *** (43.185) | −245.744 *** (30.831) | −117.177 *** (42.096) | −111.271 *** (31.804) | −0.770 * (0.441) | −0.390 (0.331) | −0.543 (0.447) | −0.625 * (0.327) | 0.007 *** (0.001) | 0.008 *** (0.001) |
Participants Aged between 56–65 years | ||||||||||
Men, n = 7708 | Women, n = 7692 | Men, n = 7708 | Women, n = 7692 | Men, n = 7708 | Women, n = 7692 | Men, n = 7708 | Women, n = 7692 | Men, n = 7708 | Women, n = 7692 | |
MAP | −174.006 *** (33.094) | −160.135 *** (28.472) | −59.050 * (33.175) | −94.255 *** (28.835) | −0.185 (0.349) | −0.410 (0.305) | 0.082 (0.356) | −0.561 * (0.306) | 0.008 *** (0.001) | 0.009 *** (0.001) |
SBP | −137.254 *** (21.699) | −98.180 *** (17.826) | −43.220 ** (21.768) | −61.805 *** (18.050) | −0.280 (0.229) | −0.339 * (0.191) | −0.034 (0.233) | −0.394 ** (0.191) | 0.005 *** (0.0004) | 0.006 *** (0.0004) |
DBP | −139.247 *** (38.773) | −166.069 *** (34.241) | −52.596 (38.834) | −90.344 *** (34.667) | 0.065 (0.409) | −0.263 (0.366) | 0.222 (0.416) | −0.489 (0.367) | 0.008 *** (0.001) | 0.009 *** (0.001) |
Participants Aged > 65 years | ||||||||||
Men, n = 1541 | Women, n = 1077 | Men, n = 1541 | Women, n = 1077 | Men, n = 1541 | Women, n = 1077 | Men, n = 1541 | Women, n = 1077 | Men, n = 1541 | Women, n = 1077 | |
MAP | −128.205 * (75.395) | −142.297 * (73.217) | −55.493 (73.421) | 23.048 (76.931) | −0.815 (0.763) | 1.481 * (0.799) | −1.134 (0.794) | 1.176 (0.774) | 0.009 *** (0.002) | 0.009 *** (0.002) |
SBP | −39.328 (46.797) | −49.280 (45.713) | −2.706 (45.547) | 5.374 (47.974) | 0.263 (0.473) | 1.070 ** (0.498) | −0.096 (0.493) | 0.776 (0.482) | 0.005 *** (0.001) | 0.005 *** (0.001) |
DBP | −202.744 ** (90.283) | −215.163 ** (87.574) | −114.477 (87.948) | 39.658 (92.110) | −2.245 ** (0.913) | 1.212 (0.957) | −2.264 ** (0.951) | 1.098 (0.927) | 0.010 *** (0.002) | 0.010 *** (0.002) |
Gray Matter Volume (mm3) | White Matter Volume (mm3) | Left Hippocampus Volume (mm3) | Right Hippocampus Volume (mm3) | White Matter Lesions Volume (mm3) | ||||||
---|---|---|---|---|---|---|---|---|---|---|
Beta (SE) | Beta (SE) | Beta (SE) | Beta (SE) | Beta (SE) | ||||||
Participants Aged ≤ 45 Years | ||||||||||
Men, n = 2220 | Women, n = 2867 | Men, n = 222 | Women, n = 2867 | Men, n = 2220 | Women, n = 2867 | Men, n = 2220 | Women, n = 2867 | Men, n = 2220 | Women, n = 2867 | |
MAP | −198.625 *** (66.470) | −208.734 *** (50.092) | 79.340 (67.656) | −59.634 (50.123) | 0.960 (0.713) | −1.165 ** (0.545) | 0.644 (0.722) | −1.145 ** (0.542) | 0.002 ** (0.001) | 0.003 *** (0.001) |
BMI | 16.382 (239.070) | −275.082 ** (134.932) | −633.982 *** (243.336) | −365.703 *** (135.014) | −0.573 (2.564) | 0.367 (1.469) | −0.718 (2.596) | 0.873 (1.460) | 0.006 ** (0.003) | 0.003 (0.002) |
MAPxBMI | −29.473 ** (13.137) | 7.608 (8.625) | −6.065 (13.371) | −2.559 (8.630) | −0.056 (0.141) | −0.039 (0.094) | 0.011 (0.143) | −0.051 (0.093) | 0.0003 (0.0002) | 0.0001 (0.0001) |
Participants Aged between 46–55 years | ||||||||||
Men, n = 5699 | Women, n = 7456 | Men, n = 5699 | Women, n = 7456 | Men, n = 5699 | Women, n = 7456 | Men, n = 5699 | Women, n = 7456 | Men, n = 5699 | Women, n = 7456 | |
MAP | −192.823 *** (40.704) | −200.841 *** (27.180) | −85.433 ** (39.624) | 0.769 (27.990) | −0.644 (0.417) | −0.320 (0.293) | −0.464 (0.422) | −0.467 (0.290) | 0.006 *** (0.001) | 0.008 *** (0.001) |
BMI | −596.787 *** (168.370) | −341.246 *** (89.410) | −769.786 *** (163.904) | −628.097 *** (92.074) | 1.111 (1.724) | −0.613 (0.963) | 2.921 * (1.744) | −0.319 (0.952) | 0.005 * (0.003) | −0.001 (0.002) |
MAP×BMI | 4.411 (9.513) | −4.452 (5.326) | 5.635 (9.260) | 2.521 (5.485) | −0.029 (0.097) | −0.020 (0.057) | −0.113 (0.099) | −0.018 (0.057) | 0.0001 (0.0001) | 0.0001 (0.0001) |
Participants Aged between 56–65 years | ||||||||||
Men, n = 7708 | Women, n = 7692 | Men, n = 7708 | Women, n = 7692 | Men, n = 7708 | Women, n = 7692 | Men, n = 7708 | Women, n = 7692 | Men, n = 7708 | Women, n = 7692 | |
MAP | −181.194 *** (34.689) | −138.683 *** (28.930) | −9.496 (34.638) | −37.344 (29.165) | −0.333 (0.366) | −0.587 * (0.310) | −0.079 (0.373) | −0.582 * (0.311) | 0.008 *** (0.001) | 0.010 *** (0.001) |
BMI | −404.863 ** (160.237) | −387.165 *** (107.476) | −714.330 *** (160.000) | −868.234 *** (108.351) | 0.522 (1.691) | 0.770 (1.152) | 1.385 (1.721) | −0.853 (1.155) | 0.009 *** (0.003) | 0.001 (0.002) |
MAP×BMI | 8.606 (8.686) | −7.511 (6.489) | −9.864 (8.674) | 4.697 (6.541) | 0.010 (0.092) | 0.008 (0.070) | −0.020 (0.093) | 0.033 (0.070) | 0.0002 (0.0002) | 0.0003 * (0.0002) |
Participants Aged > 65 years | ||||||||||
Men, n = 1541 | Women, n = 1077 | Men, n = 1541 | Women, n = 1077 | Men, n = 1541 | Women, n = 1077 | Men, n = 1541 | Women, n = 1077 | Men, n = 1541 | Women, n = 1077 | |
MAP | −111.270 (77.719) | −153.558 ** (73.907) | 31.635 (75.217) | 52.849 (77.419) | −0.833 (0.787) | 1.181 (0.806) | −0.902 (0.818) | 0.968 (0.780) | 0.010 *** (0.002) | 0.010 *** (0.002) |
BMI | 27.947 (395.892) | −199.765 (325.092) | −765.763 ** (383.148) | −606.394 * (340.537) | 2.249 (4.007) | 4.827 (3.544) | 5.229 (4.167) | 1.386 (3.430) | 0.008 (0.008) | −0.011 (0.009) |
MAP×BMI | −9.049 (22.063) | 18.236 (18.549) | −27.683 (21.353) | 0.783 (19.430) | −0.034 (0.223) | −0.173 (0.202) | −0.331 (0.232) | 0.161 (0.196) | −0.0002 (0.0005) | 0.001 (0.0005) |
Grey Matter Volume (mm3) | White Matter Volume (mm3) | Left Hippocampus Volume (mm3) | Right Hippocampus Volume (mm3) | White Matter Lesions Volume (mm3) | ||||||
---|---|---|---|---|---|---|---|---|---|---|
Beta (SE) | Beta (SE) | Beta (SE) | Beta (SE) | Beta (SE) | ||||||
Participants Aged ≤ 45 Years | ||||||||||
Men, n = 964 | Women, n = 1987 | Men, n= 964 | Women, n = 1987 | Men, n = 964 | Women, n = 1987 | Men, n= 964 | Women, n = 1987 | Men, n = 964 | Women, n = 1987 | |
Normal MAP range | −140.655 (183.520) | −243.201 ** (96.291) | 263.209 (190.018) | −95.851 (97.375) | 2.359 (1.942) | −2.016 * (1.038) | 1.640 (1.945) | −1.682 (1.028) | 0.002 (0.002) | 0.0003 (0.001) |
Normal SBP range | −42.742 (106.502) | −164.736 *** (62.863) | 23.849 (110.357) | −92.306 (63.560) | 1.444 (1.126) | −0.456 (0.679) | 1.234 (1.128) | −0.376 (0.672) | 0.002 (0.001) | 0.00005 (0.001) |
Normal DBP range | −186.480 (206.326) | −194.894 * (102.694) | 454.374 ** (213.363) | −40.338 (103.798) | 1.762 (2.184) | −2.828 ** (1.106) | 0.793 (2.187) | −2.366 ** (1.095) | −0.001 (0.002) | 0.0004 (0.001) |
Participants Aged between 46–55 years | ||||||||||
Men, n = 1980 | Women, n = 4043 | Men, n = 1980 | Women, n = 4043 | Men, n = 1980 | Women, n = 4043 | Men, n = 1980 | Women, n = 4043 | Men, n = 1980 | Women, n = 404 | |
Normal MAP range | −31.049 (127.963) | −128.719 ** (63.733) | −241.406 * (124.627) | −35.402 (64.560) | 1.144 (1.352) | −0.151 (0.685) | 2.084 (1.381) | 0.357 (0.681) | −0.001 (0.002) | 0.005 *** (0.001) |
Normal SBP range | 5.250 (70.961) | −87.950 ** (36.926) | −161.276 ** (69.080) | 33.839 (37.410) | 1.030 (0.750) | −0.058 (0.397) | 1.435 * (0.765) | 0.378 (0.394) | −0.0001 (0.001) | 0.003 *** (0.001) |
Normal DBP range | −71.526 (145.776) | −80.381 (72.517) | −129.634 (142.087) | −133.879 * (73.404) | 0.054 (1.541) | −0.181 (0.779) | 1.029 (1.574) | −0.035 (0.774) | −0.001 (0.002) | 0.005 **** (0.001) |
Participants Aged between 56–65 years | ||||||||||
Men, n = 2499 | Women, n = 3695 | Men, n = 2499 | Women, n = 3695 | Men, n = 2499 | Women, n = 3695 | Men, n = 2499 | Women, n = 3695 | Men, n = 2499 | Women, n = 3695 | |
Normal MAP range | −196.624 * (104.472) | −190.525 *** (69.524) | 69.218 (107.730) | −73.460 (70.536) | −0.417 (1.118) | −0.387 (0.751) | 0.339 (1.132) | −0.147 (0.749) | 0.008 *** (0.002) | 0.008 *** (0.001) |
Normal SBP range | −133.036 *** (51.358) | −100.866 *** (34.649) | 20.373 (52.996) | −60.706 * (35.149) | −0.243 (0.550) | −0.226 (0.375) | 0.194 (0.557) | −0.126 (0.373) | 0.005 *** (0.001) | 0.005 *** (0.001) |
Normal DBP range | −32.864 (133.890) | −133.617 (88.385) | 101.246 (137.965) | 19.338 (89.620) | −0.201 (1.432) | −0.203 (0.955) | 0.175 (1.449) | 0.053 (0.952) | 0.003 (0.002) | 0.005 *** (0.002) |
Participants Aged > 65 years | ||||||||||
Men, n = 560 | Women, n = 512 | Men, n = 560 | Women, n = 512 | Men, n = 560 | Women, n = 512 | Men, n = 560 | Women, n = 512 | Men, n = 560 | Women, n = 512 | |
Normal MAP rang | −190.065 (218.158) | −360.197 * (183.829) | 302.068 (217.392) | −82.686 (185.861) | 3.453 (2.292) | 0.497 (1.892) | 2.914 (2.291) | −1.511 (1.782) | 0.011 *** (0.004) | 0.011 ** (0.004) |
Normal SBP range | −107.070 (103.988) | −94.429 (90.647) | 124.976 (103.697) | −59.590 (91.376) | 1.821 * (1.092) | 0.334 (0.930) | 1.660 (1.092) | −0.797 (0.876) | 0.007 *** (0.002) | 0.004 * (0.002) |
Normal DBP range | −90.755 (295.256) | −625.745 ** (246.919) | 326.066 (294.230) | −1.479 (250.343) | 2.149 (3.105) | 0.099 (2.548) | 1.318 (3.103) | −1.121 (2.401) | 0.002 (0.006) | 0.013 ** (0.006) |
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Alateeq, K.; Walsh, E.I.; Abhayaratna, W.P.; Cherbuin, N. Effects of Higher Normal Blood Pressure on Brain Are Detectable before Middle-Age and Differ by Sex. J. Clin. Med. 2022, 11, 3127. https://doi.org/10.3390/jcm11113127
Alateeq K, Walsh EI, Abhayaratna WP, Cherbuin N. Effects of Higher Normal Blood Pressure on Brain Are Detectable before Middle-Age and Differ by Sex. Journal of Clinical Medicine. 2022; 11(11):3127. https://doi.org/10.3390/jcm11113127
Chicago/Turabian StyleAlateeq, Khawlah, Erin I. Walsh, Walter P. Abhayaratna, and Nicolas Cherbuin. 2022. "Effects of Higher Normal Blood Pressure on Brain Are Detectable before Middle-Age and Differ by Sex" Journal of Clinical Medicine 11, no. 11: 3127. https://doi.org/10.3390/jcm11113127