Author + information
- Received December 9, 2019
- Revision received February 3, 2020
- Accepted March 10, 2020
- Published online May 11, 2020.
- Yuan Ma, MD, PhDa,b,∗∗ (, )
- Pinar Yilmaz, MDb,c,∗,
- Daniel Bos, MD, PhDb,c,
- Deborah Blacker, MD, ScDa,d,
- Anand Viswanathan, MD, PhDe,
- M. Arfan Ikram, MD, PhDb,
- Albert Hofman, MD, PhDa,b,
- Meike W. Vernooij, MD, PhDb,c,†∗∗ ( and )
- M. Kamran Ikram, MD, PhDb,f,†
- aDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
- bDepartment of Epidemiology, Erasmus MC University Medical Center, Rotterdam, the Netherlands
- cDepartment of Radiology and Nuclear Medicine, Erasmus MC University Medical Center, Rotterdam, the Netherlands
- dDepartment of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
- eDepartment of Neurology, Massachusetts General Hospital Stroke Research Center, Harvard Medical School, Boston, Massachusetts
- fDepartment of Neurology, Erasmus MC University Medical Center, Rotterdam, the Netherlands
- ↵∗Address for correspondence:
Dr. Yuan Ma, Department of Epidemiology, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue Kresge 906, Boston, Massachusetts 02115.
- ↵∗∗Dr. Meike W. Vernooij, Department of Radiology & Nuclear Medicine, Erasmus MC University Medical Center, PO Box 2040 3000 CA Rotterdam, the Netherlands
Background Large blood pressure (BP) variability may contribute to stroke and dementia, but the mechanisms are largely unknown.
Objectives This study investigated the association of BP variation, considering its magnitude and direction, with the presence and progression of subclinical brain disease in the general population.
Methods This study included 2,348 participants age ≥55 years from a prospective cohort study. BP was measured at each visit every 3 to 4 years from 1990 onward. Brain magnetic resonance imaging (MRI) was performed at all visits from 2005 onward. The authors primarily assessed variation as the absolute difference in BP divided by the mean over 2 sequential visits for both systolic BP (SBP) and diastolic BP (DBP), and further assessed the direction of the variation. The authors investigated the multivariate-adjusted associations of BP variation with subsequent measurements of MRI markers of cerebral small vessel disease, brain tissue volumes, and white matter microstructural integrity. Longitudinal changes in these markers also were assessed.
Results A large SBP variation (top vs. bottom tertiles), measured on average 7 years preceding brain MRI, was associated with higher odds of having severe white matter hyperintensities (WMH) (odds ratio [OR]: 1.32; 95% confidence interval [CI]: 1.21 to 1.43), lacunes (OR: 1.25; 95% CI: 1.04 to 1.48), and microbleeds (OR: 1.16; 95% CI: 1.03 to 1.31). Similarly, this variation was associated with smaller total brain volume and worse white matter microstructural integrity (all p < 0.001). A large SBP variation was also associated with the progression of WMH (rate ratio [RR]: 1.14; 95% CI: 1.02 to 1.27). Higher burdens of these brain imaging markers were observed with both large rises and falls in SBP. Similar findings were observed for DBP variation.
Conclusions Elevated BP variation was associated with a wide range of subclinical brain structural changes, including MRI markers of cerebral small vessel disease, smaller brain tissue volumes, and worse white matter microstructural integrity. These subclinical brain changes could be the underlying mechanisms linking BP variation to dementia and stroke.
- blood pressure
- cerebral small vessel disease
- cerebrovascular disease
- magnetic resonance imaging
- prospective cohort study
↵∗ Drs. Ma and Yilmaz are joint first authors.
↵† Drs. Vernooij and M.K. Ikram are joint senior authors.
The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University, Rotterdam; Netherlands Organization for the Health Research and Development (ZonMw); the Research Institute for Diseases in the Elderly (RIDE); the Ministry of Education, Culture and Science; the Ministry for Health, Welfare and Sports; the European Commission (DG XII); and the Municipality of Rotterdam. This work was partially supported by an unrestricted grant from the Janssen Prevention Center. The funding organizations had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. All authors have reported that they have no relationships relevant to the contents of this paper to disclose.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC authors instructions page.
- Received December 9, 2019.
- Revision received February 3, 2020.
- Accepted March 10, 2020.
- 2020 American College of Cardiology Foundation
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