69,357 research outputs found
Reduced parenchymal cerebral blood flow is associated with greater progression of brain atrophy: The SMART-MR study
Get PDFGlobal cerebral hypoperfusion may be involved in the aetiology of brain atrophy; however, long-term longitudinal studies on this relationship are lacking. We examined whether reduced cerebral blood flow was associated with greater progression of brain atrophy. Data of 1165 patients (61 ± 10 years) from the SMART-MR study, a prospective cohort study of patients with arterial disease, were used of whom 689 participated after 4 years and 297 again after 12 years. Attrition was substantial. Total brain volume and total cerebral blood flow were obtained from magnetic resonance imaging scans and expressed as brain parenchymal fraction (BPF) and parenchymal cerebral blood flow (pCBF). Mean decrease in BPF per year was 0.22% total intracranial volume (95% CI: -0.23 to -0.21). Mean decrease in pCBF per year was 0.24 ml/min per 100 ml brain volume (95% CI: -0.29 to -0.20). Using linear mixed models, lower pCBF at baseline was associated with a greater decrease in BPF over time (p = 0.01). Lower baseline BPF, however, was not associated with a greater decrease in pCBF (p = 0.43). These findings indicate that reduced cerebral blood flow is associated with greater progression of brain atrophy and provide further support for a role of cerebral blood flow in the process of neurodegeneration
Carotid Artery Stenosis and Progression of Hemispheric Brain Atrophy: The SMART-MR Study
Get PDFINTRODUCTION: It has been hypothesized that carotid artery stenosis (CAS) may lead to greater atrophy of subserved brain regions; however, prospective studies on the impact of CAS on progression of hemispheric brain atrophy are lacking. We examined the association between CAS and progression of hemispheric brain atrophy. METHODS: We included 654 patients (57 ± 9 years) of the SMART-MR study, a prospective cohort study of patients with manifest arterial disease. Patients had baseline CAS duplex measurements and a 1.5T brain MRI at baseline and after 4 years of follow-up. Mean change in hemispheric brain volumes (% of intracranial volume [ICV]) was estimated between baseline and follow-up for left-sided and right-sided CAS across three degrees of stenosis (mild [≤29%], moderate [30-69%], and severe [≥70%]), adjusting for demographics, cerebrovascular risk factors, and brain infarcts. RESULTS: Mean decrease in left and right hemispheric brain volumes was 1.15% ICV and 0.82% ICV, respectively, over 4 years of follow-up. Severe right-sided CAS, compared to mild CAS, was associated with a greater decrease in volume of the left hemisphere (B = -0.49% ICV, 95% CI: -0.86 to -0.13) and more profoundly of the right hemisphere (B = -0.90% ICV, 95% CI: -1.27 to -0.54). This pattern was independent of cerebrovascular risk factors, brain infarcts, and white matter hyperintensities on MRI, and was also observed when accounting for the presence of severe bilateral CAS. Increasing degrees of left-sided CAS, however, was not associated with greater volume loss of the left or right hemisphere. CONCLUSIONS: Our data indicate that severe (≥70%) CAS could represent a risk factor for greater ipsilateral brain volume loss, independent of cerebrovascular risk factors, brain infarcts, or white matter hyperintensities on MRI. Further longitudinal studies in other cohorts are warranted to confirm this novel finding
External applicability of SGLT2 inhibitor cardiovascular outcome trials to patients with type 2 diabetes and cardiovascular disease
Get PDFBackground: Recent treatment guidelines support the use of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in patients with type 2 diabetes and cardiovascular disease based on the results of cardiovascular outcome trials (CVOTs). Applicability of these trials to everyday patients with type 2 diabetes and cardiovascular disease is however unknown. The aim of this study is to assess the external applicability of SGLT2i CVOTs in daily clinical practice type 2 diabetes patients with established cardiovascular disease. Methods: Trial in- and exclusion criteria from EMPA-REG OUTCOME, CANVAS, DECLARE-TIMI 58 and VERTIS-CV were applied to 1389 type 2 diabetes patients with cardiovascular disease in the Utrecht Cardiovascular Cohort-Secondary Manifestations of ARTerial disease (UCC-SMART). To evaluate the difference in cardiovascular risk (MACE) and all-cause mortality between trial eligible and ineligible patients, age and sex-adjusted Cox-regression analyses were performed. Results: After applying trial in- and exclusion criteria, 48% of UCC-SMART patients with type 2 diabetes and cardiovascular disease would have been eligible for DECLARE-TIMI 58, 35% for CANVAS, 29% for EMPA-REG OUTCOME and 21% for VERTIS-CV. Without the eligibility criteria of HbA1c, eligibility was 58–88%. For all trials the observed risk for cardiovascular events and all-cause mortality was similar in eligible and ineligible patients after adjustment for age and gender. Conclusion: A large proportion of patients with type 2 diabetes and cardiovascular disease in daily clinical practice would have been eligible for participation in the SGLT2i CVOTs. Trial eligible and ineligible patients have the same risk for MACE and all-cause mortality
Low-grade carotid artery stenosis is associated with progression of brain atrophy and cognitive decline. The SMART-MR study
Get PDFAsymptomatic low-grade carotid artery stenosis (LGCS) is a common finding in patients with manifest arterial disease, however its relationship with brain MRI changes and cognitive decline is unclear. We included 902 patients (58 ± 10 years; 81% male) enrolled in the Second Manifestations of Arterial Disease - Magnetic Resonance (SMART-MR) study without a history of cerebrovascular disease. LGCS was defined as 1-49% stenosis on baseline carotid ultrasound, whereas no LGCS (reference category) was defined as absence of carotid plaque. Brain and white matter hyperintensity (WMH) volumes and cognitive function were measured at baseline and after 4 (n = 480) and 12 years (n = 222) of follow-up. Using linear mixed-effects models, we investigated associations of LGCS with progression of brain atrophy, WMH, and cognitive decline. LGCS was associated with greater progression of global brain atrophy (estimate -0.03; 95%CI, -0.06 to -0.01; p = 0.002), and a greater decline in executive functioning (estimate -0.02; 95%CI, -0.031 to -0.01; p < 0.001) and memory (estimate -0.012; 95%CI, -0.02 to -0.001; p = 0.032), independent of demographics, cardiovascular risk factors, and incident brain infarcts on MRI. No association was observed between LGCS and progression of WMH. Our results indicate that LGCS may represent an early marker of greater future brain atrophy and cognitive decline
Prediction of Lifetime and 10-Year Risk of Cancer in Individual Patients With Established Cardiovascular Disease
Get PDFBackground: Cardiovascular disease (CVD) and cancer share many common risk factors; patients with CVD also may be at risk of developing cancer. Objectives: The aim of this study was to derive and externally validate prediction models for the estimation of lifetime and 10-year risk for total, colorectal, and lung cancer in patients with established CVD. Methods: Data from patients with established CVD from the UCC-SMART cohort (N = 7,280) were used for model development, and from the CANTOS trial (N = 9,322) for model validation. Predictors were selected based on previously published cancer risk scores, clinical availability, and presence in the derivation dataset. Fine and Gray competing risk-adjusted lifetime models were developed for the outcomes total, colorectal, and lung cancer. Results: Selected predictors were age, sex, smoking, weight, height, alcohol use, antiplatelet use, diabetes, and C-reactive protein. External calibration for the 4-year risk of lung, colorectal, and total cancer was reasonable in our models, as was discrimination with C-statistics of 0.74, 0.64, and 0.63, respectively. Median predicted lifetime and 10-year risks in CANTOS were 26% (range 1% to 52%) and 13% (range 1% to 31%) for total cancer; 4% (range 0% to 13%) and 2% (range 0% to 6%) for colorectal cancer; and 5% (range 0% to 37%) and 2% (range 0% to 24%) for lung cancer. Conclusions: Lifetime and 10-year risk of total, colorectal, and lung cancer can be estimated reasonably well in patients with established CVD with readily available clinical predictors. With additional study, these tools could be used in clinical practice to further aid in the emphasis of healthy lifestyle changes and to guide thresholds for targeted diagnostics and screening
Genetic variants associated with low-density lipoprotein cholesterol and systolic blood pressure and the risk of recurrent cardiovascular disease in patients with established vascular disease
No full textBackground and aims: Polygenic risk scores (PRSs) can be used to quantify the effect of genetic contribution to LDL-cholesterol (LDL-C) and systolic blood pressure (SBP). Several PRSs for LDL-C and SBP have been shown to be associated with cardiovascular disease (CVD) in the general population. This study aimed to evaluate the effect of an LDL-C PRS and an SBP PRS on the risk of recurrent CVD in patients with CVD. Methods: Genotyping was performed in 4,416 patients included in the UCC-SMART study. Weighted LDL-C PRS (279 LDL-C-related SNPs) and SBP PRS (425 SBP-related SNPs) were calculated. Linear regression models were used to evaluate the relation between both PRSs and LDL-C and SBP. The effects of the LDL-C PRS and SBP PRS, and its combination on the risk of recurrent CVD (stroke, myocardial infarction, and vascular death) were analyzed with Cox proportional-hazard models. Results: Per SD increase in LDL-C PRS, LDL-C increased by 0.18 mmol/L (95%CI 0.15–0.21). Per SD increase in SBP PRS, SBP increased by 3.19 mmHg (95%CI 2.60–3.78). During a follow-up of 11.7 years (IQR 9.2–15.0) 1,198 recurrent events occurred. Neither the LDL-C nor the SBP PRS were associated with recurrent CVD (HR 1.05 per SD increase in LDL-C PRS (95%CI 0.99–1.11) and HR 1.04 per SD increase in SBP PRS (95%CI 0.98–1.10)). The combination of both scores was neither associated with recurrent CVD (HR 1.09; 95%CI 0.93–1.28). Conclusions: In patients with vascular disease, LDL-C PRS and SBP PRS, both separately and in combination, were not significantly associated with recurrent CVD
The role of cognitive and brain reserve in memory decline and atrophy rate in mid and late-life: The SMART-MR study
Get PDFOBJECTIVE: Investigate associations of cognitive and brain reserve with trajectories of memory decline in mid-life and late-life, and whether the relationship of memory decline with atrophy differs as a function of reserve. METHODS: Participants were 989 Dutch middle-aged to older adults from the SMART-MR prospective cohort, followed up to 12 years with up to 3 measurements of memory and brain MRI. Education and Dutch National Adult Reading Test (DART) were used as proxies of cognitive reserve, and intracranial volume (ICV) and baseline brain parenchymal fraction (BPF) for brain reserve. Univariate growth curve models analyzed associations of reserve with memory decline, and multiple-group bivariate growth curve models tested the longitudinal brain-memory relationship as a function of reserve. Models were additionally stratified by mid-life and late-life. RESULTS: Higher DART, education, and BPF were related to a slower rate of memory decline, particularly in late-life, but ICV was not. A positive covariance indicated that an individual who undergoes atrophy also undergoes memory decline-this relationship did not differ across cognitive or brain reserve, but was not present in mid-life. Memory declined slower than brain volume, yet rates were more similar in the low DART, education, and BPF groups. DISCUSSION: Higher cognitive (DART, education) and brain reserve (BPF) work protectively in longitudinal memory change. ICV is an inappropriate proxy of brain reserve, failing to show any association with memory performance at baseline or over time. Deconstructing relationships of reserve capacities with longitudinal cognitive and brain outcomes may identify focus areas with potential for intervention
Estimating uncertainty when providing individual cardiovascular risk predictions: a Bayesian survival analysis
Get PDFBackground: Cardiovascular disease (CVD) risk scores provide point estimates of individual risk without uncertainty quantification. The objective of the current study was to demonstrate the feasibility and clinical utility of calculating uncertainty surrounding individual CVD-risk predictions using Bayesian methods. Study Design and Setting: Individuals with established atherosclerotic CVD were included from the Utrecht Cardiovascular Cohort—Secondary Manifestations of ARTerial disease (UCC-SMART). In 8,355 individuals, followed for median of 8.2 years (IQR 4.2–12.5), a Bayesian Weibull model was derived to predict the 10-year risk of recurrent CVD events. Results: Model coefficients and individual predictions from the Bayesian model were very similar to that of a traditional (‘frequentist’) model but the Bayesian model also predicted 95% credible intervals (CIs) surrounding individual risk estimates. The median width of the individual 95%CrI was 5.3% (IQR 3.6–6.5) and 17% of the population had a 95%CrI width of 10% or greater. The uncertainty decreased with increasing sample size used for derivation of the model. Combining the Bayesian Weibull model with sampled hazard ratios based on trial reports may be used to estimate individual estimates of absolute risk reduction with uncertainty measures and the probability that a treatment option will result in a clinically relevant risk reduction. Conclusion: Estimating uncertainty surrounding individual CVD risk predictions using Bayesian methods is feasible. The uncertainty regarding individual risk predictions could have several applications in clinical practice, like the comparison of different treatment options or by calculating the probability of the individual risk being below a certain treatment threshold. However, as the individual uncertainty measures only reflect sampling error and no biases in risk prediction, physicians should be familiar with the interpretation before widespread clinical adaption
The relation between healthy lifestyle changes and decrease in systemic inflammation in patients with stable cardiovascular disease
Get PDFBackground and aims: Pharmacological lowering of inflammation has proven effective in reducing recurrent cardiovascular event rates. Aim of the current study is to evaluate lifestyle changes (smoking cessation, weight loss, physical activity level increase, alcohol moderation, and a summary lifestyle improvement score) in relation to change in plasma C-reactive protein (CRP) concentration in patients with established cardiovascular disease. Methods: In total, 1794 patients from the UCC-SMART cohort with stable cardiovascular disease and CRP levels ≤10 mg/L, who returned for a follow-up study visit after median 9.9 years (IQR 5.4–10.8), were included. The relation between changes in smoking status, weight, physical activity, alcohol consumption, a summary lifestyle improvement score and change in plasma CRP concentration was evaluated with linear regression analyses. Results: Smoking cessation was related to a 0.40 mg/L decline in CRP concentration (β-coefficient −0.40; 95%CI -0.73,-0.07). Weight loss (per 1SD = 6.4 kg) and increase in physical activity (per 1 SD = 48 MET hours per week) were related to a decrease in CRP concentration (β-coefficients −0.25; 95%CI -0.33,-0.16 and −0.09; 95%CI -0.17,-0.01 per SD). Change in alcohol consumption was not related to CRP difference. Every point higher in the summary lifestyle improvement score was related to a decrease in CRP concentration of 0.17 mg/L (β-coefficient −0.17; 95%CI -0.26,-0.07). Conclusions: Smoking cessation, increase in physical activity, and weight loss are related to a decrease in CRP concentration in patients with stable cardiovascular disease. Patients with the highest summary lifestyle improvement score have the most decrease in CRP concentration. These results may indicate that healthy lifestyle changes contribute to lowering systemic inflammation, potentially leading to a lower cardiovascular risk in patients with established cardiovascular disease
Metabolic syndrome and risk of incident heart failure in non-diabetic patients with established cardiovascular disease
Get PDFBACKGROUND: In patients with established cardiovascular disease (CVD), the relation between metabolic syndrome (MetS) and incident heart failure (HF) in the absence of diabetes mellitus (DM) is largely unknown. This study assessed this relation in non-diabetic patients with established CVD. METHODS: Patients from the prospective UCC-SMART cohort with established CVD, but without DM or HF at baseline were included (n = 4653). MetS was defined according to the Adult Treatment Panel III criteria. Insulin resistance was quantified using the homeostasis model of insulin resistance (HOMA-IR). The outcome was a first hospitalization for HF. Relations were assessed using Cox proportional hazards models adjusted for established risk factors: age, sex, prior myocardial infarction (MI), smoking, cholesterol, and kidney function. RESULTS: During a median follow-up of 8.0 years, 290 cases of incident HF were observed (0.81/100 person years). MetS was significantly related to an increased risk of incident HF independent of established risk factors (hazard ratio [HR] 1.32; 95% confidence interval [CI] 1.04-1.68, HR per criterion 1.17; 95% CI 1.06-1.29), as was HOMA-IR (HR per standard deviation [SD] 1.15; 95% CI 1.03-1.29). Of the individual MetS components, only higher waist circumference independently increased the risk of HF (HR per SD 1.34; 95% CI 1.17-1.53). Relations were independent of the occurrence of interim DM and MI, and were not significantly different for HF with reduced vs preserved ejection fraction. CONCLUSION: In CVD patients without a current diagnosis of DM, MetS and insulin resistance increase the risk of incident HF independent of established risk factors
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