Endothelial Dysfunction and the Risk of Hypertension: The Multi-Ethnic Study of Atherosclerosis

Hypertension is associated with impaired endothelial function in cross-sectional studies. However, few longitudinal data exist on whether endothelial dysfunction precedes the development of hypertension. We examined the cross-sectional and longitudinal relationships between endothelial-dependent brachial artery flow-mediated dilation (FMD) and hypertension prevalence and incidence in 3500 participants from the Multi-Ethnic Study of Atherosclerosis, an ethnically diverse, community-based cohort study. At baseline, the prevalence ratios (95% CI) of hypertension from the highest to the lowest quartile of FMD were 1.00 (referent), 1.26 (1.12 to 1.40), 1.35 (1.21 to 1.52), and 1.68 (1.50 to 1.87; linear trend P<0.001). This association remained (P=0.017) after adjustment for demographics (age, sex, and ethnicity), Multi-Ethnic Study of Atherosclerosis site, and other risk factors. Of the 1869 participants without hypertension at baseline, 584 (31.3%) developed hypertension over a median follow-up of 4.8 years. The unadjusted relative risks (95% CI) of incident hypertension from the highest to the lowest quartile of FMD were 1.00 (referent), 1.38 (1.14 to 1.67), 1.44 (1.19 to 1.74), and 1.64 (1.36 to 1.97; linear trend P<0.001). However, after adjustment for demographics and Multi-Ethnic Study of Atherosclerosis site, the relationship between FMD and incident hypertension was attenuated and not statistically significant: 1.00 (referent), 1.26 (1.04 to 1.52), 1.19 (0.98 to 1.44), and 1.18 (0.97 to 1.44). The longitudinal results also did not appreciably change after adjustment for additional risk factors and baseline blood pressure levels. In this sample, reduced FMD was not an independent predictor of hypertension incidence, suggesting that impaired endothelial function does not play a major role in the development of hypertension

Associations of Aortic Distensibility and Arterial Elasticity With Long-Term Visit-to-Visit Blood Pressure Variability: The Multi-Ethnic Study of Atherosclerosis (MESA)

BACKGROUND Although higher visit-to-visit variability (VVV) of blood pressure (BP) is associated with increased cardiovascular disease risk, the physiological basis for VVV of BP is incompletely understood. METHODS We examined the associations of aortic distensibility (assessed by magnetic resonance imaging) and artery elasticity indices (determined by radial artery pulse contour analysis) with VVV of BP in 2,640 and 4,560 participants, respectively, from the Multi-Ethnic Study of Atherosclerosis. Arterial measures were obtained at exam 1. BP readings were taken at exam 1 and at 3 follow-up visits at 18-month intervals (exams 2, 3, and 4). VVV was defined as the SD about each participant’s mean systolic BP (SBP) across visits. RESULTS The mean SDs of SBP were inversely associated with aortic distensibility: 7.7, 9.9, 10.9, and 13.2mm Hg for quartiles 4, 3, 2, and 1 of aortic distensibility, respectively (P trend < 0.001). This association remained significant after adjustment for demographics, cardiovascular risk factors, mean SBP, and antihypertensive medication use (P trend < 0.01). In a fully adjusted model, lower quartiles of large artery and small artery elasticity (LAE and SAE) indices were also associated with higher mean SD of SBP (P trend = 0.02 for LAE; P trend < 0.001 for SAE). CONCLUSIONS In this multiethnic cohort, functional alterations of central and peripheral arteries were associated with greater long-term VVV of SBP

Particulate matter components and subclinical atherosclerosis: common approaches to estimating exposure in a Multi-Ethnic Study of Atherosclerosis cross-sectional study

Abstract Background Concentrations of outdoor fine particulate matter (PM2.5) have been associated with cardiovascular disease. PM2.5 chemical composition may be responsible for effects of exposure to PM2.5. Methods Using data from the Multi-Ethnic Study of Atherosclerosis (MESA) collected in 2000–2002 on 6,256 US adults without clinical cardiovascular disease in six U.S. metropolitan areas, we investigated cross-sectional associations of estimated long-term exposure to total PM2.5 mass and PM2.5 components (elemental carbon [EC], organic carbon [OC], silicon and sulfur) with measures of subclinical atherosclerosis (coronary artery calcium [CAC] and right common carotid intima-media thickness [CIMT]). Community monitors deployed for this study from 2007 to 2008 were used to estimate exposures at baseline addresses using three commonly-used approaches: (1) nearest monitor (the primary approach), (2) inverse-distance monitor weighting and (3) city-wide average. Results Using the exposure estimate based on nearest monitor, in single-pollutant models, increased OC (effect estimate [95% CI] per IQR: 35.1 μm [26.8, 43.3]), EC (9.6 μm [3.6,15.7]), sulfur (22.7 μm [15.0,30.4]) and total PM2.5 (14.7 μm [9.0,20.5]) but not silicon (5.2 μm [−9.8,20.1]), were associated with increased CIMT; in two-pollutant models, only the association with OC was robust to control for the other pollutants. Findings were generally consistent across the three exposure estimation approaches. None of the PM measures were positively associated with either the presence or extent of CAC. In sensitivity analyses, effect estimates for OC and silicon were particularly sensitive to control for metropolitan area. Conclusion Employing commonly-used exposure estimation approaches, all of the PM2.5 components considered, except silicon, were associated with increased CIMT, with the evidence being strongest for OC; no component was associated with increased CAC. PM2.5 chemical components, or other features of the sources that produced them, may be important in determining the effect of PM exposure on atherosclerosis. These cross-sectional findings await confirmation in future work employing longitudinal outcome measures and using more sophisticated approaches to estimating exposure.http://deepblue.lib.umich.edu/bitstream/2027.42/112668/1/12940_2013_Article_651.pd

Data abstractions for decision tree induction

AbstractWhen descriptions of data values in a database are too concrete or too detailed, the computational complexity needed to discover useful knowledge from the database will be generally increased. Furthermore, discovered knowledge tends to become complicated. A notion of data abstraction seems useful to resolve this kind of problems, as we obtain a smaller and more general database after the abstraction, from which we can quickly extract more abstract knowledge that is expected to be easier to understand. In general, however, since there exist several possible abstractions, we have to carefully select one according to which the original database is generalized. An inadequate selection would make the accuracy of extracted knowledge worse.From this point of view, we propose in this paper a method of selecting an appropriate abstraction from possible ones, assuming that our task is to construct a decision tree from a relational database. Suppose that, for each attribute in a relational database, we have a class of possible abstractions for the attribute values. As an appropriate abstraction for each attribute, we prefer an abstraction such that, even after the abstraction, the distribution of target classes necessary to perform our classification task can be preserved within an acceptable error range given by user.By the selected abstractions, the original database can be transformed into a small generalized database written in abstract values. Therefore, it would be expected that, from the generalized database, we can construct a decision tree whose size is much smaller than one constructed from the original database. Furthermore, such a size reduction can be justified under some theoretical assumptions. The appropriateness of abstraction is precisely defined in terms of the standard information theory. Therefore, we call our abstraction framework Information Theoretical Abstraction.We show some experimental results obtained by a system ITA that is an implementation of our abstraction method. From those results, it is verified that our method is very effective in reducing the size of detected decision tree without making classification errors so worse

Prevalence and prognostic impact of subclinical cardiovascular disease in individuals with the metabolic syndrome and diabetes

Dostępne dane dotyczące występowania i znaczenia prognostycznego subklinicznej postaci choroby sercowo-naczyniowej (CVD), u pacjentów z zespołem metabolicznym są ograniczone. W prezentowanej pracy zbadano częstość występowania subklinicznej choroby sercowo-naczyniowej u 1945 uczestników próby Framingham Offspring Study (śr. wieku 58 lat, 59% uczestników stanowiły kobiety) z wykorzystaniem elektrokardiografii, echokardiografii, ultra ultrasonografii tętnic szyjnych, wskaźnika ciśnienia tętniczego kostka&#8211;ramię oraz wydalania albumin z moczem. W pracy oceniono w sposób prospektywny częstość występowania subklinicznej choroby sercowo-naczyniowej związanej z zespołem metabolicznym i cukrzycą, w zależności od obecności subklinicznej postaci tego schorzenia lub jej braku. Przekrojowo u 51% z 581 uczestników z zespołem metabolicznym zdiagnozowano subkliniczną formę choroby sercowo-naczyniowej w przynajmniej jednym z badań dodatkowych, co było częstsze niż u chorych bez zespołu metabolicznego [iloraz szans skorygowany pod względem wielu zmiennych 2,06 (95% CI: 1,67&#8211;2,55); p < 0,0001]. W trakcie dalszej obserwacji klinicznej (śr. 7,2 lat) jawna klinicznie choroba sercowo-naczyniowa rozwinęła się u 139 pacjentów, 59% tej liczby stanowiły osoby z zespołem metabolicznym (10,2%). Uogólniając, występowanie zespołu metabolicznego było związane ze zwiększonym ryzykiem występowania CVD [iloraz ryzyka skorygowany pod względem wielu zmiennych (HR, hazard ratio) 1,61 (95% CI: 1,12&#8211;2,33)]. U pacjentów z zespołem metabolicznym oraz subkliniczną postacią choroby sercowo-naczyniowej zaobserwowano zwiększone ryzyko wystąpienia jawnej klinicznie postaci choroby sercowo-naczyniowej [2,67 (1,62&#8211;4,41) w porównaniu z chorymi bez zdiagnozowanego zespołu metabolicznego, cukrzycy lub subklinicznej formy choroby sercowo-naczyniowej]. Zaobserwowano także mniejszy związek występowania zespołu metabolicznego z rozwinięciem się choroby sercowo-naczyniowej u pacjentów bez subklinicznej postaci CVD [HR 1,59 (95% CI: 0,87&#8211;2,90)]. Podobne zmniejszenie ryzyka wystąpienia choroby sercowo-naczyniowej u pacjentów bez subklinicznej postaci CVD obserwowano u chorych na cukrzycę. Występowanie subklinicznej formy CVD stanowiło istotny predyktor rozwinięcia się jawnej klinicznie choroby sercowo-naczyniowej u pacjentów bez zespołu metabolicznego lub cukrzycy [1,93 (1,15&#8211;3,24)]. W niniejszym populacyjnym badaniu osób z zespołem metabolicznym zaobserwowano częstsze występowanie subklinicznej postaci miażdżycy, co prawdopodobnie przyczynia się do wyższego ryzyka wystąpienia jawnej klinicznie postaci CVD związanej z tym schorzeniem.Data are limited regarding prevalence and prognostic significance of subclinical cardiovascular disease (CVD) in individuals with metabolic syndrome. We investigated prevalence of subclinical CVD in 1,945 Framingham Offspring Study participants (mean age 58 years; 59% women) using electrocardiography, echocardiography, carotid ultrasound, ankle-brachial blood pressure, and urinary albumin excretion. We prospectively evaluated the incidence of CVD associated with metabolic syndrome and diabetes according to presence versus absence of subclinical disease. Cross-sectionally, 51% of 581 participants with metabolic syndrome had subclinical disease in at least one test, a frequency higher than individuals without metabolic syndrome [multivariable- adjusted odds ratio 2.06 (95% CI: 1.67- 2.55); p < 0.0001). On follow-up (mean 7.2 years), 139 individuals developed overt CVD, including 59 with metabolic syndrome (10.2%). Overall, metabolic syndrome was associated with increased CVD risk [multivariableadjusted hazards ratio (HR) 1.61 (95% CI: 1.12-2.33)]. Participants with metabolic syndrome and subclinical disease experienced increased risk of overt CVD [2.67 (1.62-4.41) compared with those without metabolic syndrome, diabetes, or subclinical disease], whereas the association of metabolic syndrome with CVD risk was attenuated in absence of subclinical disease [HR 1.59 (95% CI: 0.87&#8211;2.90)]. A similar attenuation of CVD risk in absence of subclinical disease was observed also for diabetes. Subclinical disease was a significant predictor of overt CVD in participants without metabolic syndrome or diabetes [1.93 (1.15-3.24)]. In our community-based sample, individuals with metabolic syndrome have a high prevalence of subclinical atherosclerosis that likely contributes to the increased risk of overt CVD associated with the condition

Meta-analysis of genome-wide association studies from the CHARGE consortium identifies common variants associated with carotid intima media thickness and plaque

Carotid intima media thickness (cIMT) and plaque determined by ultrasonography are established measures of subclinical atherosclerosis that each predicts future cardiovascular disease events. We conducted a meta-analysis of genome-wide association data in 31,211 participants of European ancestry from nine large studies in the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. We then sought additional evidence to support our findings among 11,273 individuals using data from seven additional studies. In the combined meta-analysis, we identified three genomic regions associated with common carotid intima media thickness and two different regions associated with the presence of carotid plaque (P < 5 × 10 -8). The associated SNPs mapped in or near genes related to cellular signaling, lipid metabolism and blood pressure homeostasis, and two of the regions were associated with coronary artery disease (P < 0.006) in the Coronary Artery Disease Genome-Wide Replication and Meta-Analysis (CARDIoGRAM) consortium. Our findings may provide new insight into pathways leading to subclinical atherosclerosis and subsequent cardiovascular events

Alcohol consumption and common carotid intima-media thickness: the USE-IMT study

Aims: Epidemiological evidence indicates a protective effect of light to moderate alcohol consumption compared to non-drinking and heavy drinking. Although several mechanisms have been suggested, the effect of alcohol on atherosclerotic changes in vessel walls is unclear. Therefore, we explored the relationship between alcohol consumption and common carotid intima media thickness, a marker of early atherosclerosis in the general population. Methods: Individual participant data from eight cohorts, involving 37,494 individuals from the USE-IMT collaboration were used. Multilevel age and sex adjusted linear regression models were applied to estimate mean differences in common carotid intima-media thickness (CIMT) with alcohol consumption. Results: The mean age was 57.9 years (SD 8.6) and the mean CIMT was 0.75 mm (SD 0.177). About, 40.5% reported no alcohol consumed, and among those who drank, mean consumption was 13.3 g per day (SD 16.4). Those consuming no alcohol or a very small amount (10 g per day, after adjusting for a range of confounding factors. Conclusion: In this large CIMT consortium, we did not find evidence to support a protective effect of alcohol on CIMT