Circulating interleukin-10 and risk of cardiovascular events: a prospective study in the elderly at risk

<p><b>Objective:</b> The goal of this study was to examine the association of the antiinflammatory interleukin-10 (IL-10) with risk of cardiovascular disease (CVD).</p> <p><b>Methods and Results:</b> In the PROSPER (PROspective Study of Pravastatin in the Elderly at Risk) cohort, we related baseline concentrations of circulating IL-10 to risk of CVD events in a nested case (n=819)-control (n=1618) study of 3.2 years of follow-up. Circulating IL-10 showed few strong associations with classical risk factors but was positively correlated with IL-6 and C-reactive protein. IL-10 was positively associated with risk of CVD events (odds ratio [OR] 1.17, 95% CI 1.05 to 1.31 per unit increase in log IL-10) after adjusting for classical risk factors and C-reactive protein. Furthermore, IL-10 was associated more strongly with CVD risk among those with no previous history of CVD (OR 1.42, 95% CI 1.18 to 1.70), compared with those with previous CVD (OR 1.04, 95% CI 0.90 to 1.19; P=0.018). Overall, IL-10 showed a modest ability to add discrimination to classical risk factors (C-statistic +0.005, P=0.002).</p> <p><b>Conclusion:</b> Baseline circulating levels of the antiinflammatory IL-10 are positively associated with risk of CVD among the elderly without prior CVD events, although the association is less evident in those with a history of CVD. Additional epidemiological and mechanistic studies investigating the role of IL-10 in CVD are warranted.</p&gt

Genetic variations in the PCSK9 gene in relation to cholesterol levels, cognitive function and clinical events in an elderly population

Pathophysiology, epidemiology and therapy of agein

MRI evaluation of the relationship between carotid artery endothelial shear stress and brain white matter lesions in migraine

Although white matter lesions are frequently detected in migraine patients, underlying mechanisms remain unclear. Low carotid artery endothelial shear stress has been associated with white matter lesions. We aimed to investigate the association between carotid artery endothelial shear stress and white matter lesions in migraine. In 40 elderly migraine patients (n = 29 females, 75 years [SD 3]) and 219 controls (n = 80 females, 74 years [SD 3]) from the PROSPER-MRI study, carotid artery endothelial shear stress was estimated on 1.5 T gradient-echo phase contrast MRI. White matter lesion volumes were calculated from structural MRI scans. Analyses were adjusted for age, sex, cardiovascular risk factors and cardiovascular disease. Migraine patients had lower mean endothelial shear stress compared to controls (0.90 [SD 0.15] vs. 0.98 [SD 0.16] Pa; P = 0.03). The association between mean endothelial shear stress and white matter lesion volume was greater for the migraine group than control group (P for interaction = 0.05). Within the migraine group, white matter lesion volume increased with decreasing endothelial shear stress (beta-0.421; P = 0.01). In conclusion, migraine patients had lower endothelial shear stress which was associated with higher white matter lesion volume

Associations Between Thrombin Generation and the Risk of Cardiovascular Disease in Elderly Patients: Results From the PROSPER Study

Cardiolog

Circulating interleukin-6 concentration and cognitive decline in old age: the PROSPER study

<p>Background: Inflammation is involved in the pathogenesis of cardiovascular disease and cognitive decline. Interleukin-6 (IL-6) has a role in cardiovascular disease, but the association of IL-6 concentration and the functional IL-6 -174 polymorphism with cognitive decline has not been demonstrated unequivocally. The objective of this study was to investigate the associations between both high concentration of IL-6 and the -174 promoter polymorphism, and increased cognitive decline in old age.</p> <p>Methods: Over 5000 participants of the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) with a mean age of 75 years and a history of cardiovascular disease or its risk factors were included in this study. We determined baseline concentrations of IL-6 and genotype of the IL-6 -174 polymorphism, of which the C allele was previously shown to be associated with higher circulating concentrations of IL-6. A cognitive test battery was administered at baseline and repeatedly during follow-up (mean 39 months).</p> <p>Results: In the cross-sectional analysis of 5653 participants, higher IL-6 concentration was associated with worse executive cognitive function (P < 0.001), independent of cardiovascular disease status and risk factors. No association was found between IL-6 concentration and memory function (P > 0.14). In the prospective analysis, higher IL-6 concentration was associated with an increased rate of cognitive decline in both executive function (P = 0.002) and memory function (P = 0.002), again independent of cardiovascular disease status and risk factors. Although not associated with IL-6 concentrations, the IL-6 -174 CC genotype was associated with worse performance on the Stroop test (P = 0.045).</p> <p>Conclusions: Higher circulating levels of IL-6 were associated with worse cognitive function and steeper cognitive decline and provide preliminary genetic evidence for a potential causal association. The findings support the importance of the need for further investigation of the IL-6 pathway in cognitive decline.</p&gt

Infratentorial Microbleeds Another Sign of Microangiopathy in Migraine

Pathophysiology, epidemiology and therapy of agein

Increased amygdalar and hippocampal volumes in elderly obese individuals with or at risk of cardiovascular disease

Background: The basal ganglia, hippocampus, and thalamus are involved in the regulation of human feeding behavior. Recent studies have shown that obesity [body mass index (BMI; in kg/m(2)) > 30] is associated with loss of gray and white matter. Objective: It is unknown whether the subcortical brain structures that are actually involved in feeding behavior also show volume changes in obesity. Therefore, the purpose of this study was to evaluate the volumes of the basal ganglia, hippocampus, and thalamus in obesity. Design: Three-dimensional T1-weighted magnetic resonance imaging scans of the brain were analyzed by using automatic segmentation to measure volumes of the nucleus accumbens, globus pallidus, amygdala, putamen, caudate nucleus, thalamus, and hippocampus in 471 subjects (mean age: 74.4 y; 56% men). Results: Obese subjects had larger left (P = 0.013) and right (P = 0.003) amygdalar volumes and a larger left hippocampal volume (P = 0.040) than did normal-weight subjects (BMI, 25). None of the other subcortical structures differed in size between these groups. After correction for age, sex, smoking, hypertension, and pravastatin use, BMI was associated with left (beta = 0.175, P = 0.001) and right (beta = 0.157, P = 0.001) amygdalar volumes and with left hippocampal volume (beta = 0.121, P = 0.016). Conclusions: This study showed that the amygdala and hippocampus are enlarged in obesity. In consideration of the function of these structures, this finding may indicate that hedonic memories could be of major importance in the regulation of feeding. Because of the cross-sectional design, cause and effect could not be discriminated in this study. Am J Clin Nutr 2011;93:1190-5.Vascular Biology and Interventio

Lipoprotein-associated phospholipase A₂ inflammatory biomarkers, and risk of cardiovascular disease in the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER)

<p><b>Objective</b> <br>Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an inflammatory biomarker that circulates mainly bound to LDL. We evaluated the association of Lp-PLA2 with vascular events in the elderly where the importance of LDL is diminished as a risk factor for coronary disease.</br></p> <p><b>Methods</b> <br>Mass and activity of Lp-PLA2 were related to risk over 3.2 years for vascular events (definite or suspected death from CHD, non-fatal MI, fatal or non-fatal stroke) in the 2804 men and 3000 women age 70–82 years in the Prospective Study of Pravastatin in the Elderly (PROSPER).</br></p> <p><b>Results</b> <br>Lp-PLA2 showed a moderate, positive association with risk of a vascular event with hazard ratios of 1.25 (confidence interval (CI) 1.02–1.54) for mass and 1.39 (CI 1.14–1.70) for activity for top versus bottom quartile. Risk associations were attenuated when classical risk factors, lipids and inflammatory markers – C-reactive protein and white cell count – were included in the models. Lp-PLA<sub>2</sub> was unrelated to stroke risk. Inclusion of all three inflammatory markers in multivariate models negated the association of HDL cholesterol with risk (hazard ratio 0.98; CI 0.88–1.10) and increased prediction of coronary events; the C statistic rose from 63.2% to 64.4% (P < 0.001).</br></p> <p><b>Conclusion</b> <br>In elderly people Lp-PLA<sub>2</sub>, alongside other inflammatory indices, is a potential biomarker for vascular events, particularly CHD.</br></p&gt

Associations between Total Cerebral Blood Flow and Age Related Changes of the Brain

Background and Purpose: Although total cerebral blood flow (tCBF) is known to be related to age, less is known regarding the associations between tCBF and the morphologic changes of the brain accompanying cerebral aging. The purpose of this study was to investigate whether total cerebral blood flow (tCBF) is related to white matter hyperintensity (WMH) volume and/or cerebral atrophy. Furthermore, we investigate whether tCBF should be expressed in mL/min, as was done in all previous MR studies, or in mL/100 mL/min, which yielded good results in precious SPECT, PET and perfusion MRI studies investigating regional cerebral blood flow. Materials and Methods: Patients were included from the nested MRI sub-study of the PROSPER study. Dual fast spin echo and FLAIR images were obtained in all patients. In addition, single slice phase contrast MR angiography was used for flow measurements in the internal carotids and vertebral arteries. tCBF was expressed in both mL/min and mL/100 mL/min. Results: We found a significant correlation between tCBF in mL/min and both age (r = -.124; p = p <=.001) and parenchymal volume (r = 0.430; p <=.001). We found no association between tCBF in mL/min and %-atrophy (r = -.077; p <=.103) or total WMH volume (r = -.069; p =.148). When tCBF was expressed in mL/100 mL/min the correlation between tCBF and age was no longer found (r = -.001; p =.985). Multivariate regression analyses corrected for age showed a significant correlation between tCBF in mL/100 mL/min and WMH volume (r = -.106; p =.044). No significant association between tCBF in mL/100 mL/min and %- atrophy was found. Conclusion: From this study we conclude that, when evaluating tCBF alterations due to various pathologies, tCBF should in mL/100 mL/min instead of mL/min. Furthermore, changes or differences in WMH volume should be accounted for.Pathophysiology, epidemiology and therapy of agein