Carotid stiffness is associated with retinal microvascular dysfunction-The Maastricht study.

OBJECTIVE: This study investigated whether arterial stiffening is a determinant of subtle retinal microvascular changes that precede diabetic retinopathy. RESEARCH DESIGN AND METHODS: This study used cross-sectional data from the Maastricht Study, a type 2 diabetes-enriched population-based cohort study. We used multivariable linear regression analysis to investigate, in individuals without and with type 2 diabetes, the associations of carotid distensibility coefficient and carotid-femoral pulse wave velocity with retinal microvascular diameters and flicker light-induced dilation and adjusted for cardiovascular and lifestyle risk factors. RESULTS: The retinal microvascular diameter study population consisted of N = 2434 participants (51.4% men, mean ± SD age 59.8 ± 8.1 years, and 28.1% type 2 diabetes). No measures of arterial stiffness were significantly associated with microvascular diameters. Greater carotid distensibility coefficient (i.e., lower carotid stiffness) was significantly associated with greater retinal arteriolar flicker light-induced dilation (per standard deviation, standardized beta [95% CI] 0.06 [0.00; 0.12]) and non-significantly, but directionally similarly, associated with greater retinal venular flicker light-induced dilation (0.04 [-0.02; 0.10]). Carotid-femoral pulse wave velocity (i.e., aortic stiffness) was not associated with retinal microvascular flicker light-induced dilation. The associations between carotid distensibility coefficient and retinal arteriolar and venular flicker light-induced dilation were two- to threefold stronger in individuals with type 2 diabetes than in those without. CONCLUSION: In this population-based study greater carotid, but not aortic, stiffness was associated with worse retinal flicker light-induced dilation and this association was stronger in individuals with type 2 diabetes. Hence, carotid stiffness may be a determinant of retinal microvascular dysfunction.

Cardiovagal baroreflex sensitivity, blood pressure and blood pressure variability - the Maastricht study.

OBJECTIVE: Low baroreflex sensitivity (BRS) has been hypothesized to underlie high blood pressure (BP) and greater BP variability on the longer term, but evidence is scarce. In addition, these associations may differ by sex and (pre)diabetes. Therefore, we investigated whether cardiovagal BRS is associated with short- to mid-term mean BP and BP variability, and differs according to sex and (pre)diabetes. METHODS: Cross-sectional data from the population-based Maastricht study (age 60 ±â€Š8 years, 52% men), where office ( n  = 2846), 24-h ( n  = 2404) and 7-day BP measurements ( n  = 2006) were performed. Spontaneous BRS was assessed by cross-correlating systolic BP and instantaneous heart rate. We used linear regression with adjustments for age, sex, BP or BP variability, and cardiovascular risk factors. RESULTS: With regard to BP, 1-SD (standard deviation) lower BRS (-5.75 ms/mmHg) was associated with higher office, 24-h and 7-day systolic BP (2.22 mmHg [95% confidence interval [CI]: 1.59; 2.80], 0.95 mmHg [0.54; 1.36], and 1.48 mmHg [0.99; 1.97], respectively) and diastolic BP (1.31 mmHg [0.97; 1.66], 0.57 mmHg [0.30; 0.84], and 0.86 mmHg [0.54; 1.17], respectively). Per 1-SD lower BRS, these associations were stronger in women (0.5-1.5 mmHg higher compared to men), and weaker in those with type 2 diabetes (1-1.5 mmHg lower compared to normal glucose metabolism). With regard to BP variability, BRS was not consistently associated with lower BP variability. CONCLUSIONS: Lower cardiovagal BRS is associated with higher mean BP from the short- to mid-term range, and not consistently with BP variability. The associations with mean BP are stronger in women and weaker in those with type 2 diabetes.

Urinary Sodium Excretion and Salt Intake Are Not Associated With Blood Pressure Variability in a White General Population.

Background Salt restriction may lower blood pressure variability (BPV), but previous studies have shown inconsistent results. Therefore, we investigated in an observational study and intervention trial whether urinary sodium excretion and salt intake are associated with 24-hour BPV. Methods and Results We used data from the cross-sectional population-based Maastricht Study (n=2652; 60±8 years; 52% men) and from a randomized crossover trial (n=40; 49±11 years; 33% men). In the observational study, we measured 24-hour urinary sodium excretion and 24-hour BPV and performed linear regression adjusted for age, sex, mean blood pressure, lifestyle, and cardiovascular risk factors. In the intervention study, participants adhered to a 7-day low- and high-salt diet (50 and 250 mmol NaCl/24 h) with a washout period of 14 days, 24-hour BPV was measured during each diet. We used linear mixed models adjusted for order of diet, mean blood pressure, and body mass index. In the observational study, 24-hour urinary sodium excretion was not associated with 24-hour systolic or diastolic BPV (ß, per 1 g/24 h urinary sodium excretion: 0.05 mm Hg [95% CI, -0.02 to 0.11] and 0.04 mm Hg [95% CI, -0.01 to 0.09], respectively). In the intervention trial, mean difference in 24-hour systolic and diastolic BPV between the low- and high-salt diet was not statistically significantly different (0.62 mm Hg [95% CI, -0.10 to 1.35] and 0.04 mm Hg [95% CI, -0.54 to 0.63], respectively). Conclusions Urinary sodium excretion and salt intake are not independently associated with 24-hour BPV. These findings suggest that salt restriction is not an effective strategy to lower BPV in the White general population. Registration URL: https://clinicaltrials.gov/ct2/show/NCT02068781.

Exercise SBP response and incident depressive symptoms: The Maastricht Study.

OBJECTIVE: : An exaggerated exercise SBP, which is potentially modifiable, may be associated with incident depressive symptoms via an increased pulsatile pressure load on the brain. However, the association between exaggerated exercise SBP and incident depressive symptoms is unknown. Therefore, we examined whether exaggerated exercise SBP is associated with a higher risk of depressive symptoms over time. METHODS: : We used longitudinal data from the population-based Maastricht Study, with only individuals free of depressive symptoms at baseline included (n = 2121; 51.3% men; age 59.5 ±â€Š8.5 years). Exercise SBP was measured at baseline with a submaximal exercise cycle test. We calculated a composite score of exercise SBP based on four standardized exercise SBP measures: SBP at moderate workload, SBP at peak exercise, SBP change per minute during exercise and SBP 4 min after exercise. Clinically relevant depressive symptoms were determined annually at follow-up and defined as a Patient Health Questionnaire score of at least 10. RESULTS: : After a mean follow-up of 3.9 years, 175 participants (8.3%) had incident clinically relevant depressive symptoms. A 1 SD higher exercise SBP composite score was associated with a higher incidence of clinically relevant depressive symptoms [hazard ratio: 1.27 (95% confidence interval: 1.04-1.54)]. Results were adjusted for age, sex, education level, glucose metabolism status, lifestyle, cardiovascular risk factors, resting SBP and cardiorespiratory fitness. CONCLUSION: : A higher exercise SBP response is associated with a higher incidence of clinically relevant depressive symptoms.

Both Prediabetes and Type 2 Diabetes Are Associated With Lower Heart Rate Variability: The Maastricht Study.

OBJECTIVE: Low heart rate variability (HRV), a marker for cardiac autonomic dysfunction, is a known feature of type 2 diabetes, but it remains incompletely understood whether this also applies to prediabetes or across the whole glycemic spectrum. Therefore, we investigated the association among prediabetes, type 2 diabetes, and measures of glycemia and HRV. RESEARCH DESIGN AND METHODS: In the population-based Maastricht Study (n = 2,107; mean ± SD age 59 ± 8 years; 52% men; normal glucose metabolism [n = 1,226], prediabetes [n = 331], and type 2 diabetes [n = 550, oversampled]), we determined 24-h electrocardiogram-derived HRV in time and frequency domains (individual z-scores, based upon seven and six variables, respectively). We used linear regression with adjustments for age, sex, and major cardiovascular risk factors. RESULTS: After adjustments, both time and frequency domain HRV were lower in prediabetes and type 2 diabetes as compared with normal glucose metabolism (standardized ß [95% CI] for time domain: -0.15 [-0.27; -0.03] and -0.34 [-0.46; -0.22], respectively, P for trend <0.001; for frequency domain: -0.14 [-0.26; -0.02] and -0.31 [-0.43; -0.19], respectively, P for trend <0.001). In addition, 1-SD higher glycated hemoglobin, fasting plasma glucose, and 2-h postload glucose were associated with lower HRV in both domains (time domain: -0.16 [-0.21; -0.12], -0.16 [-0.21; -0.12], and -0.15 [-0.20; -0.10], respectively; frequency domain: -0.14 [-0.19; -0.10], -0.14 [-0.18; -0.09], and -0.13 [-0.18; -0.08], respectively). CONCLUSIONS: Both prediabetes and type 2 diabetes were independently associated with lower HRV. This is further substantiated by independent continuous associations between measures of hyperglycemia and lower HRV. These data strongly suggest that cardiac autonomic dysfunction is already present in prediabetes.

Blood pressure variability and microvascular dysfunction: the Maastricht Study.

BACKGROUND: Microvascular dysfunction (MVD) contributes to stroke, dementia, depression, retinopathy and chronic kidney disease. However, the determinants of MVD are incompletely understood. Greater blood pressure variability (BPV) may be one such determinant. METHODS AND RESULTS: We used cross-sectional data of The Maastricht Study (n = 2773, age 59.9 years; 51.9% men) to investigate whether greater very short- to mid-term BPV is associated with various MVD measures. We standardized and averaged within-visit, 24-h and 7-day BPV into a systolic and a diastolic BPV composite score. MVD measures included a composite score of MRI cerebral small vessel disease (CSVD) features (total brain parenchymal volume, white matter hyperintensity volume, lacunar infarcts and cerebral microbleeds), a composite score of flicker light-induced retinal arteriolar and venular dilation response, albuminuria, heat-induced skin hyperemia and a composite score of plasma biomarkers of MVD (sICAM-1, sVCAM-1, sE-selectin and von Willebrand Factor). We used linear regression adjusted for age, sex, glucose metabolism status, mean 24-h systolic or DBP, cardiovascular risk factors and antihypertensive medication. We found that higher systolic and diastolic BPV composite scores (per SD) were associated with higher albuminuria [higher ratio, 1.04 (95% CI 1.00-1.08) and 1.07 (1.03-1.11), respectively], but not with other measures of MVD tested. CONCLUSION: Greater systolic and diastolic BPV was associated with higher albuminuria, but not with CSVD features, flicker light-induced retinal arteriolar and venular dilation response, heat-induced skin hyperemia and plasma biomarkers of MVD. This suggests that the microvasculature of the kidneys is most vulnerable to the detrimental effects of greater BPV.

Greater Blood Pressure Variability Is Associated With Lower Cognitive Performance.

An increasing number of individuals will face age-related cognitive difficulties because life expectancy has increased. It is, therefore, important to identify modifiable risk factors for cognitive impairment. Very short-term to mid-term blood pressure variability (BPV) may be such a factor because it may cause cerebral ischemia. To this end, we investigated whether greater systolic and diastolic BPV are cross-sectionally associated with memory function (n=1804), information processing speed (n=1793), and executive function (n=1780) in 40- to 75-year-old individuals from The Maastricht Study. A composite BPV-index was derived by standardizing within-visit, 24-hour, and 7-day BPV. We performed linear regression with adjustments for age, sex, educational level, 24-hour systolic or diastolic pressure, and cardiovascular risk factors. We found that a 1-SD greater systolic BPV was not associated with information processing speed (ß [SD difference], -0.10; 95% CI, -0.14 to 0.06), or executive function (-0.09; 95% CI, -0.20 to 0.02) but was marginally associated with lower memory function (-0.11; 95% CI, -0.21 to 0.00). A 1-SD greater diastolic BPV was associated with lower information processing speed (-0.10; 95% CI, -0.20 to -0.00) and executive function (-0.12; 95% CI, -0.22 to -0.01) and marginally associated with lower memory function (-0.09; 95% CI, -0.20 to 0.01). These effects on cognitive performance are equivalent to ≈3 additional years of aging. In conclusion, greater very short-term to mid-term diastolic and, to a lesser extent, systolic BPV may be a modifiable risk factor for cognitive deterioration in 40- to 75-year-old, community-dwelling individuals.

Blood Pressure Variability, Arterial Stiffness, and Arterial Remodeling.

Greater very short- to midterm blood pressure variability (BPV) has been associated with an increased cardiovascular disease risk, especially stroke. However, this link remains incompletely understood. We hypothesized that increased arterial stiffness and maladaptive carotid arterial remodeling may underlie this association. We, therefore, investigated the association between very short- to midterm systolic BPV, aortic and carotid stiffness and carotid arterial remodeling using cross-sectional data from The Maastricht Study (aged 60±8 years; 53% men). Aortic (carotid-femoral pulse wave velocity, n=1671) and carotid stiffness (ultrasonography, n=1690) were assessed. A composite index of systolic BPV was derived by standardizing and averaging systolic within-visit, 24-hour, and 7-day BPV. We performed linear regression analyses with adjustment for age, sex, glucose metabolism status, mean arterial pressure, and cardiovascular risk factors. A 1-SD greater systolic BPV was statistically significantly associated with 0.10 m/s (95% CI, 0.01-0.20) greater carotid-femoral pulse wave velocity, but not with carotid distensibility (-0.033×10-3/kPa [-0.255 to 0.190]). In addition, a 1-SD greater systolic BPV was statistically significantly associated with greater carotid circumferential wall tension (0.84 dyne/cm [0.51-1.17]), circumferential wall stress (0.79 kPa [0.031-1.27]), and intima-media thickness (8.6 µm [1.0-16.3]). These results are indicative of maladaptive carotid remodeling, as circumferential wall tension and stress were not normalized despite greater intima-media thickness. In conclusion, greater very short- to midterm BPV is associated with greater aortic stiffness and maladaptive carotid arterial remodeling, but not with carotid stiffness. These findings may explain, at least partially, the increased BPV-associated cardiovascular disease risk, in particular stroke.

Blood pressure variability in individuals with and without (pre)diabetes: The Maastricht Study.

OBJECTIVE: The mechanisms associating (pre)diabetes and cardiovascular disease (CVD) are incompletely understood. We hypothesize that greater blood pressure variability (BPV) may underlie this association, due to its association with (incident) CVD. Therefore, we investigated the association between (pre)diabetes and very short-term to mid-term BPV, that is within-visit, 24-h and 7-day BPV. METHODS: Cross-sectional data from The Maastricht Study [normal glucose metabolism (NGM), n = 1924; prediabetes, n = 511; type 2 diabetes mellitus (T2DM), n = 975; 51% men, aged 60 ±â€Š8 years]. We determined SD for within-visit BPV (n = 3244), average real variability for 24-h BPV (n = 2699) day (0900-2100 h) and night (0100-0600 h) separately, and SD for 7-day BPV (n = 2259). Differences in BPV as compared with NGM were assessed by multiple linear regressions with adjustment for potential confounders. RESULTS: In T2DM, the average systolic/diastolic values of within-visit, 24-h and 7-day BPV were 4.8/2.6, 10.5/7.3 and 10.4/6.5 mmHg, respectively, and in prediabetes 4.9/2.6, 10.3/7.0 and 9.4/5.9 mmHg, respectively. T2DM was associated with greater nocturnal systolic BPV [0.42 mmHg (95% confidence interval: 0.05-0.80)], and greater 7-day systolic [0.76 mmHg (0.32-1.19)] and diastolic BPV [0.65 mmHg (0.29-1.01)], whereas prediabetes was associated with greater within-visit systolic BPV only [0.35 mmHg (0.06-0.65)], as compared with NGM. CONCLUSION: Both T2DM and prediabetes are associated with slightly greater very short-term to mid-term BPV, which may, according to previous literature, explain a small part of the increased CVD risk seen in (pre)diabetes. Nevertheless, these findings do not detract from the fact that very short-term to mid-term BPV is substantial and important in individuals with and without (pre)diabetes.

Stenotrophomonas maltophilia ventilator-associated pneumonia. A retrospective matched case-control study.

BACKGROUND: Stenotrophomonas maltophilia is increasingly identified in critically ill patients, but it is considered a pathogen with limited pathogenicity and it is therefore infrequently targeted. This study explores whether S. maltophilia may cause ventilator-associated pneumonia (VAP) and whether it affects intensive care unit (ICU) mortality and 28-day mortality when compared to VAP caused by other Gram-negative bacilli. METHODS: Retrospective analysis of a 19-year prospectively collected database. Stenotrophomonas maltophilia as a cause was considered in VAP-suspected cases when S. maltophilia growth of ≥10(4) cfu/ml was detected in bronchoalveolar lavage fluid analysis. Cases were matched on hospital, gender, age and acute physiology and chronic health evaluation II score in a 1:3 ratio with controls from the same database suffering from VAP caused by other Gram-negative bacilli. RESULTS: Eight cases met the inclusion criteria, of which three were labelled as 'probable' SM-VAP and three as 'possible' SM-VAP. These six patients constitute 1.8% of all VAPs in the studied period. No significant differences in baseline characteristics and duration of mechanical ventilation (p = 0.68), length of stay in the ICU (p = 0.55) and hospital (p = 0.84) between cases and controls were identified between cases and controls. Intensive care unit mortality odds ratio was 1.7 (p = 0.55; 95% CI 0.3-10.5) and 28-day mortality odds ratio was 1.4 (p = 0.70; 95% CI 0.2-9.1). CONCLUSIONS: Stenotrophomonas maltophilia is a possible, yet infrequent cause of VAP. No outcome differences were found when compared to matched VAP caused by other Gram-negative bacilli.