Subclinical Magnetic Resonance Imaging Markers of Cerebral Small Vessel Disease in Relation to Office and Ambulatory Blood Pressure Measurements

Background: Twenty-four-hour and nighttime blood pressure (BP) levels are more strongly associated with cardiovascular risk than office or daytime BP measurements. However, it remains undocumented which of the office and ambulatory BP measurements have the strongest association and predictive information in relation to the presence of type I, or arteriolosclerosis type, cerebral small vessel diseases (CSVD). Methods: A subset of 429 participants from the Maracaibo Aging Study [aged ≥40 years (women, 73.7%; mean age, 59.3 years)] underwent baseline brain magnetic resonance imaging (MRI) to visualize CSVD, which included log-transformed white matter hyperintensities (log-WMH) volume and the presence (yes/no) of lacunes, cerebral microbleeds (CMB), or enlarged perivascular spaces (EPVS). Linear and logistic regression models were applied to examine the association between CSVD and each +10-mmHg increment in the office and ambulatory systolic BP measurements. Improvement in the fit of nested logistic models was assessed by the log-likelihood ratio and the generalized R 2 statistic. Results: Office and ambulatory systolic BP measurements were related to log-WMH (β-correlation coefficients ≥0.08; P \u3c 0.001). Lacunes and CMB were only associated with ambulatory systolic BP measurements (odds ratios [OR] ranged from 1.31 [95% confidence interval, 1.10-1.55] to 1.46 [1.17-1.84], P ≤ 0.003). Accounted for daytime systolic BP, both the 24-h (β-correlation, 0.170) and nighttime (β-correlation, 0.038) systolic BP measurements remained related to log-WMH. When accounted for 24-h or daytime systolic BP levels, the nighttime systolic BP retained the significant association with lacunes (ORs, 1.05-1.06; 95% CIs, ≥1.01 to ≤ 1.13), whereas the 24-h and daytime systolic BP levels were not associated with lacunes after adjustments for nighttime systolic BP (ORs, ≤ 0.88; 95% CI, ≥0.77 to ≤ 1.14). On top of covariables and office systolic BP, ambulatory systolic BP measurements significantly improved model performance (1.05% ≥ R 2 ≤ 3.82%). Compared to 24-h and daytime systolic BP, nighttime systolic BP had the strongest improvement in the model performance; for WMH (1.46 vs. 1.05%) and lacunes (3.06 vs. ≤ 2.05%). Conclusions: Twenty-four-hour and nighttime systolic BP were the more robust BP measurements associated with CSVD, but the nighttime systolic BP level had the strongest association. Controlling ambulatory BP levels might provide additional improvement in the prevention of CSVD

Cognitive Decline Associated with Longitudinal Changes in 24-h Ambulatory Blood Pressure Variability

Background: Cognitive decline has been associated with variability in blood pressure (BP). However, whether the increment of the BP variability during follow-up precedes cognitive decline remains undocumented. We aimed this study to investigate cognitive decline in relation to longitudinal changes in 24-h reading-to-reading BP variability. Methods: We conducted an observational longitudinal study that included 717 dementia-free participants from the Maracaibo Aging Study who underwent follow-up assessment in both 24-h ambulatory BP monitoring and cognitive tests between 1998 and 2015. Cognitive domains consisted of selective reminding tests (total, long-term, short-term, and recognition memory) and the Mini-Mental State Examination (MMSE). Cognitive decline was a longitudinal decrease in cognitive scores. Participants underwent 24-h ambulatory BP monitoring between 2-4 times – with at least one-year interval. Systolic and diastolic BP variability was studied during 24-h and divided into daytime (from 06h00 to 23h00), and nighttime (23h00 to 06h00) periods. To account for BP level, we used variability independent of the mean (VIM) to compute systolic and diastolic BP variability. Other measures of BP variability included the nocturnal BP drop in comparison to the daytime BP level, which was estimated as the night-to-day ratio. Statistics included multivariate linear regression mixed models. Results: Overall, the mean age was 65.6±7.36 years old and 66.5% (n=447) of the participants were women. In mixed models, a decline in all memory domains was associated with greater variability in the 24-h, daytime, and nighttime systolic BP during follow-up, with an estimated decline in cognitive scores ranging from -0.2 to -0.04 points per unit increase in VIM systolic BP during follow-up (P values ranged from 0.022 to 0.003). Decline in total, short-term, and MMSE memory domains was associated with greater 24-h and daytime diastolic BP variability (P≤0.015). A lower night-to-day dipping ratio during follow-up increased the risk of cognitive decline, with a -5.8 to -1.6 decline in long-term memory and MMSE scores; respectively (P≤0.037). Conclusions: Cognitive decline associates with greater reading-to-reading 24-h BP variability and lower falls in nocturnal BP over time. These findings might be indicative of deteriorated regulatory mechanisms to maintain steady BP levels as individuals age

Normal-tension glaucomatous optic neuropathy is related to blood pressure variability in the Maracaibo Aging Study

Hypoperfusion of the optic nerve might be involved in the pathogenesis of normal-tension glaucomatous optic neuropathy (GON). Mean arterial pressure (MAP) drives ocular perfusion, but no previous studies have addressed the risk of GON in relation to blood pressure (BP) variability, independent of BP level. In a cross-sectional study, 93 residents of Maracaibo, Venezuela, underwent optical coherence tomography, visual field assessments and 24-h ambulatory BP monitoring between 2011 and 2016. We investigated the association of normal-tension GON with or without visual field defects with reading-to reading variability of 24-h MAP, as captured by variability independent of the MAP level (VIMmap). Odds ratios (ORs) were adjusted for 24-h MAP level and for a propensity score of up to five risk factors. Among the 93 participants (87.1% women; mean age, 61.9 years), 26 had open-angle normal-tension GON at both eyes; 14 had visual field defects; and 19 did not have visual field defects. The OR ratios for normal-tension GON, expressed per 1-SD increment in VIMmap (2 mm Hg), were 2.17 (95% confidence interval, 1.33–3.53) unadjusted; 2.20 (1.35–3.61) adjusted for 24-h MAP level only; 1.93 (1.10–3.41) with additional adjustment for age, educational attainment, high-density lipoprotein (HDL) cholesterol and office hypertension; and 1.95 (1.10–3.45) in models including intraocular pressure. We confirmed our a priori hypothesis that BP variability, most likely operating via hypoperfusion of the optic nerve, is associated with normal-tension GON. 24-H ambulatory BP monitoring might therefore help stratify the risk of normal-tension GON

Glaucomatous Optic Neuropathy Associated with Nocturnal Dip in Blood Pressure: Findings from the Maracaibo Aging Study

Purpose—To determine which nocturnal blood pressure (BP) parameters (low levels or extreme dipper status) are associated with an increased risk of glaucomatous damage in Hispanics. Design—Observational cross-sectional study. Participants—A subset (n=93) of the participants from the Maracaibo Aging Study (MAS) who met the study eligibility criteria were included. These participants — who were at least 40 years of age — had measurements for optical tomography coherence, visual field tests, 24-hour BP, office BP, and intraocular pressureHg. Methods—Univariate and multivariate logistic regression analyses under the generalized estimating equations (GEE) framework were used to examine the relationships between glaucomatous damage and BP parameters, with particular attention to drops in nocturnal BP. Main Outcome Measures—Glaucomatous optic neuropathy (GON) based on the presence of optic nerve damage and visual field defects. Results—The mean age was 61.9 years, and 87.1% were women. Of 185 eyes evaluated, 50 (27.0%) had signs of GON. Individuals with GON had significantly lower 24-hour and nighttime diastolic BP levels than those without. However, results of the multivariate GEE models indicated that the glaucomatous damage was not related to the average systolic or diastolic BP levels measured over 24 hours, daytime, or nighttime. In contrast, extreme drops in nighttime systolic and diastolic BP (\u3e20% compared with daytime BP) were significant risk factors for glaucomatous damage (odds ratio=19.78 and 5.55, respectively). Conclusions—In this population, the link between nocturnal BP and GON is determined by extreme dipping effects rather than low nocturnal BP levels alone. Further studies considering extreme drops in nocturnal BP in individuals at high risk of glaucoma are warranted

Nighttime Blood Pressure Interacts with APOE Genotype to Increase the Risk of Incident Dementia of the Alzheimer's Type in Hispanics

Background: Dementia of the Alzheimer’s type (DAT) impacts Hispanics disproportionately, with almost a twofold elevated risk of developing DAT, as well as earlier onset of the disease, than in non-Hispanic Whites. However, the role of main risk factors for DAT, such as APOE ɛ4 and blood pressure (BP) levels, remains uncertain among Hispanics. Objective: To investigate the association of APOE ɛ4 and BP levels, measures with 24 h ambulatory BP monitoring, with incidence of DAT in an elderly cohort of Hispanics. Methods:1,320 participants from the Maracaibo Aging Study, free of dementia at the baseline, and with ambulatory BP measurements and APOE genotype available were included. Adjusted Cox proportional models were performed to examine 1) the incidence of DAT and 2) the relationship between BP levels and DAT according to APOE genotypes. Models were adjusted by competing risk of death before the onset of DAT. Model performance was assessed by likelihood test. Results: The average follow-up time was 5.3 years. DAT incidence was 5.8 per 1000 person-year. APOE ɛ4 carriers had a higher risk of DAT. In unadjusted analyses, conventional, 24 h, and nighttime systolic BP levels were significantly higher in participants who developed DAT and of APOE ɛ4 carriers (p \u3c 0.05). After adjustment for competing for risk, only higher nighttime systolic BP was associated with DAT incidence, but only among subjects carrying APOE ɛ4. Conclusion: In this Hispanic population, both APOE ɛ4 genotype and assessment of nocturnal systolic BP (rather than diurnal or office BP) were necessary to estimate DAT risk

White matter hyperintensities mediate the association of nocturnal blood pressure with cognition

Objective To test the hypotheses that hypertension and nocturnal blood pressure are related to white matter hyperintensity (WMH) volume, an MRI marker of small vessel cerebrovascular disease, and that WMHburden statistically mediates the association of hypertension and dipping status with memory functioning, we examined the relationship of hypertension and dipping status on WMH volume and neuropsychological test scores in middle-aged and older adults. Methods Participants from the community-based Maracaibo Aging Study received ambulatory 24-hour blood pressure monitoring, structural MRI, and neuropsychological assessment. Four hundred thirty-five participants (mean ± SD age 59 ± 13 years, 71% women) with available ambulatory blood pressure, MRI, and neuropsychological data were included in the analyses. Ambulatory blood pressure was used to define hypertension and dipping status (i.e., dipper, nondipper, and reverse dipper based on night/day blood pressure ratio1, respectively). Outcome measures included regional WMH and memory functioning derived from a neuropsychological test battery. Results The majority of the participants (59%) were hypertensive. Ten percent were reverse dippers, and 40% were nondippers. Reverse dipping in the presence of hypertension was associated with particularly elevated periventricular WMH volume (F2,423 = 3.78, p = 0.024) and with lowered memory scores (F2,423 = 3.911, p = 0.021). Periventricular WMH volume mediated the effect of dipping status and hypertension on memory (β = −4.1, 95% confidence interval −8.7 to −0.2, p \u3c 0.05). Conclusion Reverse dipping in the presence of hypertension is associated with small vessel cerebrovascular disease, which, in turn, mediates memory functioning. These results point toward reverse dipping as a marker of poor nocturnal blood pressure control, particularly among hypertensive individuals, with potentially pernicious effects on cerebrovascular health and associated cognitive function

SUBCLINICAL MAGNETIC RESONANCE IMAGING MARKERS OF CEREBRAL SMALL VESSEL DISEASE IN RELATION TO AMBULATORY BLOOD PRESSURE MEASUREMENTS

OBJECTIVE: 24-h and nighttime blood pressure (BP) levels are the strongest BP measurements associated with cardiovascular risk. However, it remains undocumented which of the ambulatory BP measurements have the strongest association and predictive information in relation to the presence of cerebral small vessel diseases (CSVD). DESIGN AND METHOD: A subset of Maracaibo Aging Study with 429 participants [aged 40 years or older (women, 73.7%; mean age, 59.3y)] underwent baseline brain magnetic resonance imaging to visualize CSVD, which included log-transformed white matter hyperintensities (log-WMH), the presence (yes/no) of silent brain infarcts (SBI), cerebral microbleeds (CMB), or enlarged perivascular spaces (EPVS). Linear and logistic regression models were applied to examine the association between CSVD and each + 10 mmHg increment in the office and ambulatory systolic BP. Improvement in the fit of nested logistic models was assessed by the log-likelihood ratio and the generalized R2 statistic. RESULTS: Office and ambulatory systolic BP measurements were related to log-WMH (beta correlation coefficients above 0.08; P = 1.01to = 0.77to< = 1.14). On top of covariables and office systolic BP, ambulatory systolic BP measurements significantly improved model performance (R2<3.82%). Compared to 24-h and daytime SBP, nighttime systolic BP had the strongest improvement in the model performance; for WMH (1.46% vs. 1.05%) and SBI (3.06% vs. below 2.05%). CONCLUSIONS: 24-h and nighttime systolic BP were the more robust BP measurements associated with CSVD, but for log-WMH and SBI, the nighttime systolic BP level had the strongest association. Controlling ambulatory BP levels might provide additional improvement in the prevention of CSVD

Subclinical Magnetic Resonance Imaging Markers of Cerebral Small Vessel Disease in Relation to Office and Ambulatory Blood Pressure Measurements

Background: Twenty-four-hour and nighttime blood pressure (BP) levels are more strongly associated with cardiovascular risk than office or daytime BP measurements. However, it remains undocumented which of the office and ambulatory BP measurements have the strongest association and predictive information in relation to the presence of type I, or arteriolosclerosis type, cerebral small vessel diseases (CSVD). Methods: A subset of 429 participants from the Maracaibo Aging Study [aged ≥40 years (women, 73.7%; mean age, 59.3 years)] underwent baseline brain magnetic resonance imaging (MRI) to visualize CSVD, which included log-transformed white matter hyperintensities (log-WMH) volume and the presence (yes/no) of lacunes, cerebral microbleeds (CMB), or enlarged perivascular spaces (EPVS). Linear and logistic regression models were applied to examine the association between CSVD and each +10-mmHg increment in the office and ambulatory systolic BP measurements. Improvement in the fit of nested logistic models was assessed by the log-likelihood ratio and the generalized R2 statistic. Results: Office and ambulatory systolic BP measurements were related to log-WMH (β-correlation coefficients ≥0.08; P < 0.001). Lacunes and CMB were only associated with ambulatory systolic BP measurements (odds ratios [OR] ranged from 1.31 [95% confidence interval, 1.10-1.55] to 1.46 [1.17–1.84], P ≤ 0.003). Accounted for daytime systolic BP, both the 24-h (β-correlation, 0.170) and nighttime (β-correlation, 0.038) systolic BP measurements remained related to log-WMH. When accounted for 24-h or daytime systolic BP levels, the nighttime systolic BP retained the significant association with lacunes (ORs, 1.05–1.06; 95% CIs, ≥1.01 to ≤ 1.13), whereas the 24-h and daytime systolic BP levels were not associated with lacunes after adjustments for nighttime systolic BP (ORs, ≤ 0.88; 95% CI, ≥0.77 to ≤ 1.14). On top of covariables and office systolic BP, ambulatory systolic BP measurements significantly improved model performance (1.05% ≥ R2 ≤ 3.82%). Compared to 24-h and daytime systolic BP, nighttime systolic BP had the strongest improvement in the model performance; for WMH (1.46 vs. 1.05%) and lacunes (3.06 vs. ≤ 2.05%). Conclusions: Twenty-four-hour and nighttime systolic BP were the more robust BP measurements associated with CSVD, but the nighttime systolic BP level had the strongest association. Controlling ambulatory BP levels might provide additional improvement in the prevention of CSVD