Abstract

Background and Purpose- Studies of causes of cerebral small vessel disease (SVD) should fully adjust for blood pressure (BP), but most etiological studies use a single BP measurement or history of hypertension, which might underestimate the role of hypertension. In patients with transient ischemic attack and ischemic stroke, we therefore compared the associations of baseline and long-term premorbid BP with measures of SVD on magnetic resonance imaging brain. Methods- We studied 1009 transient ischemic attack/ischemic stroke patients who had a brain magnetic resonance imaging, in the population-based OXVASC (Oxford Vascular Study), and related baseline and 20-year premorbid BP (median: 15 readings/patient) to the total SVD score on imaging. Results- SVD score was associated with increasing mean baseline systolic BP (SBP; odds ratio of top versus bottom BP quartile: 2.28; [95% CI, 1.62-3.21]; P<0.0001) and with prior hypertension (2.53; [95% CI, 2.01-3.20]; P<0.0001), but the association was much stronger with mean premorbid SBP (6.09; [95% CI, 4.34-8.55]; P<0.0001). Mean diastolic BP at baseline was negatively associated with SVD score (0.71; [95% CI, 0.51-1.00]; P=0.050), and a positive association was only evident for diastolic BP 10 to 20 years previously (3.35; [95% CI, 2.33-4.84]; both P<0.0001). Relationships between overall mean premorbid BP and SVD burden were strongest in patients age <70 (SBP: 6.99; 4.11-11.86; diastolic BP: 3.13; 1.95-5.07; both P<0.0001) versus ≥70 years (2.37; 1.42-3.94; P=0.001; and 1.16; 0.74-1.84; P=0.52). Conclusions- Mean premorbid SBP is more strongly associated with SVD burden than baseline SBP or history of hypertension, and baseline diastolic BP yields a misleading estimate of the likely etiological importance of midlife hypertension for the subsequent development of SVD. Studies of novel potential etiological factors for SVD should aim to adjust for long-term prior BP, and trials of BP lowering with only a few years of follow-up may underestimate the overall impact on SVD.

Highlights

  • Background and PurposeStudies of causes of cerebral small vessel disease (SVD) should fully adjust for blood pressure (BP), but most etiological studies use a single BP measurement or history of hypertension, which might underestimate the role of hypertension

  • SVD score was associated with increasing mean baseline systolic BP (SBP; odds ratio of top versus bottom BP quartile: 2.28; [95% CI, 1.62–3.21]; P

  • Mean diastolic BP at baseline was negatively associated with SVD score (0.71; [95% CI, 0.51–1.00]; P=0.050), and a positive association was only evident for diastolic BP 10 to 20 years previously (3.35; [95% CI, 2.33–4.84]; both P

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Summary

Methods

We studied 1009 transient ischemic attack/ischemic stroke patients who had a brain magnetic resonance imaging, in the population-based OXVASC (Oxford Vascular Study), and related baseline and 20-year premorbid BP (median: 15 readings/patient) to the total SVD score on imaging. We prospectively studied patients with TIA/ischemic stroke from OXVASC. OXVASC is an ongoing population-based study of all acute vascular events occurring within a population of 92 728 individuals, irrespective of age, who are registered with 100 general practitioners in 9 general practices of Oxfordshire, United Kingdom.[18] The analysis includes 1080 consecutive cases of TIA/ischemic stroke recruited from November 1, 2004, to September 30, 2014, who had an MRI brain imaging. The imaging protocol of OXVASC has been described in detail elsewhere.[19,20] Briefly, from April 1, 2002, to March 31, 2010 (phase 1), MRI and magnetic resonance angiography was performed in selected patients when clinically indicated. From April 1, 2010 onwards (phase 2), brain MRI and magnetic resonance angiography became the firstline imaging methods

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