End-stage kidney disease in patients with clinically manifest vascular disease; incidence and risk factors: results from the UCC-SMART cohort study

Background: Patients with cardiovascular disease (CVD) are at increased risk of end-stage kidney disease (ESKD). Insights into the incidence and role of modifiable risk factors for end-stage kidney disease may provide means for prevention in patients with cardiovascular disease. Methods: We included 8402 patients with stable cardiovascular disease. Incidence rates (IRs) for end-stage kidney disease were determined stratified according to vascular disease location. Cox proportional hazard models were used to assess the risk of end-stage kidney disease for the different determinants. Results: Sixty-five events were observed with a median follow-up of 8.6 years. The overall incidence rate of end-stage kidney disease was 0.9/1000 person-years. Patients with polyvascular disease had the highest incidence rate (1.8/1000 person-years). Smoking (Hazard ratio (HR) 1.87; 95% CI 1.10–3.19), type 2 diabetes (HR 1.81; 95% CI 1.05–3.14), higher systolic blood pressure (HR 1.37; 95% CI 1.24–1.52/10 mmHg), lower estimated glomerular filtration rate (eGFR) (HR 2.86; 95% CI 2.44–3.23/10 mL/min/1.73 m ) and higher urine albumin/creatinine ratio (uACR) (HR 1.19; 95% CI 1.15–1.23/10 mg/mmol) were independently associated with elevated risk of end-stage kidney disease. Body mass index (BMI), waist circumference, non-HDL-cholesterol and exercise were not independently associated with risk of end-stage kidney disease. Conclusions: Incidence of end-stage kidney disease in patients with cardiovascular disease varies according to vascular disease location. Several modifiable risk factors for end-stage kidney disease were identified in patients with cardiovascular disease. These findings highlight the potential of risk factor management in patients with manifest cardiovascular disease. Graphic abstract: [Figure not available: see fulltext.].

Pharmacological therapies in post stroke recovery: Recommendations for future clinical trials

Stroke is a leading cause of serious long-term disability in adults and is the second leading cause of death worldwide. Early reperfusion and neuroprotection techniques have been the focus of much effort with the aim of very acute treatment of the stroke. Targeting different mechanisms, pharmacological therapies have the potential to reduce disability in a large fraction of patients who survive the acute stroke. The brain's capacity to reorganize after stroke through plasticity mechanisms can be modulated by pharmacological agents. A number of therapeutic interventions are under study, including small molecules, growth factors, and monoclonal antibodies. Recently it has been shown that the SSRI fluoxetine improved motor deficit in patients with ischaemic stroke and hemiplegia which appeared to be independent of the presence of depression. In this context, it is of major importance to support innovative research in order to promote the emergence of new pharmacological treatments targeting neurological recovery after stroke, as opposed to acute de-occlusion and neuroprotection. This paper is the work of a group of 14 scientists with aim of (1) addressing key areas of the basic and clinical aspects of human brain plasticity after stroke and potential pharmacological targets for recovery, (2) asking questions about the most appropriate characteristics of clinical trials testing drugs in post stroke recovery and (3) proposing recommendations for future clinical trials. © 2013 Springer-Verlag Berlin Heidelberg

Lifestyle changes and kidney function: A 10-year follow-up study in patients with manifest cardiovascular disease

BACKGROUND: Patients with cardiovascular disease (CVD) are at higher risk of kidney function decline. The current study aimed to examine the association of lifestyle changes with kidney function decline in patients with manifest CVD. METHODS: A total of 2260 patients from the Utrecht Cardiovascular Cohort-Second Manifestations of ARTerial disease cohort with manifest CVD who returned for a follow-up visit after a median of 9.9 years were included. The relation between change in lifestyle factors (smoking, alcohol consumption, physical activity and obesity) and change in kidney function (eGFR and uACR) was assessed using linear regression models. RESULTS: An increase in body mass index (β -2.81; 95% CI -3.98; -1.63 per 5 kg/m2 ) and for men also an increase in waist circumference (β -0.87; 95% CI -1.28; -0.47 per 5 cm) were significantly associated with a steeper decline in eGFR over 10 years. Continuing smoking (β -2.44, 95% CI -4.43; -0.45) and recent smoking cessation during follow-up (β -3.27; 95% CI -5.20; -1.34) were both associated with a steeper eGFR decline compared to patients who remained as non- or previous smokers from baseline. No significant association was observed between physical exercise or alcohol consumption and kidney function decline. No significant relation between any lifestyle factor and change in uACR was observed. CONCLUSIONS: In patients with CVD, continuing smoking, recent smoking cessation and an increase in obesity markers were related to a steeper kidney function decline. Although no definite conclusions from this study can be drawn, the results support the importance of encouraging weight loss and smoking cessation in high-risk patients as a means of slowing down kidney function decline

Risk, Clinical Course, and Outcome of Ischemic Stroke in Patients Hospitalized With COVID-19: A Multicenter Cohort Study

BACKGROUND AND PURPOSE: The frequency of ischemic stroke in patients with coronavirus disease 2019 (COVID-19) varies in the current literature, and risk factors are unknown. We assessed the incidence, risk factors, and outcomes of acute ischemic stroke in hospitalized patients with COVID-19. METHODS: We included patients with a laboratory-confirmed SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) infection admitted in 16 Dutch hospitals participating in the international CAPACITY-COVID registry between March 1 and August 1, 2020. Patients were screened for the occurrence of acute ischemic stroke. We calculated the cumulative incidence of ischemic stroke and compared risk factors, cardiovascular complications, and in-hospital mortality in patients with and without ischemic stroke. RESULTS: We included 2147 patients with COVID-19, of whom 586 (27.3%) needed treatment at an intensive care unit. Thirty-eight patients (1.8%) had an ischemic stroke. Patients with stroke were older but did not differ in sex or cardiovascular risk factors. Median time between the onset of COVID-19 symptoms and diagnosis of stroke was 2 weeks. The incidence of ischemic stroke was higher among patients who were treated at an intensive care unit (16/586; 2.7% versus nonintensive care unit, 22/1561; 1.4%; P=0.039). Pulmonary embolism was more common in patients with (8/38; 21.1%) than in those without stroke (160/2109; 7.6%; adjusted risk ratio, 2.08 [95% CI, 1.52–2.84]). Twenty-seven patients with ischemic stroke (71.1%) died during admission or were functionally dependent at discharge. Patients with ischemic stroke were at a higher risk of in-hospital mortality (adjusted risk ratio, 1.56 [95% CI, 1.13–2.15]) than patients without stroke. CONCLUSIONS: In this multicenter cohort study, the cumulative incidence of acute ischemic stroke in hospitalized patients with COVID-19 was ≈2%, with a higher risk in patients treated at an intensive care unit. The majority of stroke patients had a poor outcome. The association between ischemic stroke and pulmonary embolism warrants further investigation

Patients with diffuse idiopathic skeletal hyperostosis have an increased burden of thoracic aortic calcifications

OBJECTIVES: DISH has been associated with increased coronary artery calcifications and incident ischaemic stroke. The formation of bone along the spine may share pathways with calcium deposition in the aorta. We hypothesized that patients with DISH have increased vascular calcifications. Therefore we aimed to investigate the presence and extent of DISH in relation to thoracic aortic calcification (TAC) severity. METHODS: This cross-sectional study included 4703 patients from the Second Manifestation of ARTerial disease cohort, consisting of patients with cardiovascular events or risk factors for cardiovascular disease. Chest radiographs were scored for DISH using the Resnick criteria. Different severities of TAC were scored arbitrarily from no TAC to mild, moderate or severe TAC. Using multivariate logistic regression, the associations between DISH and TAC were analysed with adjustments for age, sex, BMI, diabetes, smoking status, non-high-density lipoprotein cholesterol, cholesterol lowering drug usage, renal function and blood pressure. RESULTS: A total of 442 patients (9.4%) had evidence of DISH and 1789 (38%) patients had TAC. The prevalence of DISH increased from 6.6% in the no TAC group to 10.8% in the mild, 14.3% in the moderate and 17.1% in the severe TAC group. After adjustments, DISH was significantly associated with the presence of TAC [odds ratio (OR) 1.46 [95% CI 1.17, 1.82)]. In multinomial analyses, DISH was associated with moderate TAC [OR 1.43 (95% CI 1.06, 1.93)] and severe TAC [OR 1.67 (95% CI 1.19, 2.36)]. CONCLUSIONS: Subjects with DISH have increased TACs, providing further evidence that patients with DISH have an increased burden of vascular calcifications

Cohort profile: the Utrecht Cardiovascular Cohort-Second Manifestations of Arterial Disease (UCC-SMART) Study-an ongoing prospective cohort study of patients at high cardiovascular risk in the Netherlands

PURPOSE: The Utrecht Cardiovascular Cohort-Second Manifestations of Arterial Disease (UCC-SMART) Study is an ongoing prospective single-centre cohort study with the aim to assess important determinants and the prognosis of cardiovascular disease progression. This article provides an update of the rationale, design, included patients, measurements and findings from the start in 1996 to date. PARTICIPANTS: The UCC-SMART Study includes patients aged 18-90 years referred to the University Medical Center Utrecht, the Netherlands, for management of cardiovascular disease (CVD) or severe cardiovascular risk factors. Since September 1996, a total of 14 830 patients have been included. Upon inclusion, patients undergo a standardised screening programme, including questionnaires, vital signs, laboratory measurements, an ECG, vascular ultrasound of carotid arteries and aorta, ankle-brachial index and ultrasound measurements of adipose tissue, kidney size and intima-media thickness. Outcomes of interest are collected through annual questionnaires and adjudicated by an endpoint committee. FINDINGS TO DATE: By May 2022, the included patients contributed to a total follow-up time of over 134 000 person-years. During follow-up, 2259 patients suffered a vascular endpoint (including non-fatal myocardial infarction, non-fatal stroke and vascular death) and 2794 all-cause deaths, 943 incident cases of diabetes and 2139 incident cases of cancer were observed up until January 2020. The UCC-SMART cohort contributed to over 350 articles published in peer-reviewed journals, including prediction models recommended by the 2021 European Society of Cardiology CVD prevention guidelines. FUTURE PLANS: The UCC-SMART Study guarantees an infrastructure for research in patients at high cardiovascular risk. The cohort will continue to include about 600 patients yearly and follow-up will be ongoing to ensure an up-to-date cohort in accordance with current healthcare and scientific knowledge. In the near future, UCC-SMART will be enriched by echocardiography, and a food frequency questionnaire at baseline enabling the assessment of associations between nutrition and CVD and diabetes

The Clinical Phenotype of Vascular Cognitive Impairment in Patients with Type 2 Diabetes Mellitus

Background: Type 2 diabetes mellitus (T2DM) increases the risk of vascular cognitive impairment (VCI). It is unknown which type of vascular lesions and co-morbid etiologies, in particular Alzheimer’s disease pathology, are associated with T2DM in patients with VCI, and how this relates to cognition and prognosis. Objective: To compare brain MRI and cerebrospinal fluid (CSF) markers, cognition, and prognosis in patients with possible VCI with and without T2DM. Methods: We included 851 memory clinic patients with vascular brain injury on MRI (i.e., possible VCI) from a prospective cohort study (T2DM: n = 147, 68.4±7.9 years, 63% men; no T2DM: n = 704, 67.6±8.5 years, 52% men). At baseline, we assessed between-group differences in brain MRI abnormalities, CSF markers of Alzheimer’s disease, and cognitive profile. After two years follow-up, we compared occurrence of cognitive decline, stroke, and death. Results: The distribution of clinical diagnoses did not differ between patients with and without T2DM. T2DM patients had more pronounced brain atrophy (total and white matter volume), and more lacunar infarcts, whereas microbleeds were less common (all p < 0.05). CSF amyloid-β levels were similar between the groups. T2DM patients performed worse on working memory (effect size: – 0.17, p = 0.03) than those without, whereas performance on other domains was similar. During follow-up, risk of further cognitive decline was not increased in T2DM.∥Conclusion: In patients with possible VCI, presence of T2DM is related to more pronounced brain atrophy and a higher burden of lacunar infarcts, but T2DM does not have a major impact on cognitive profile or prognosis

Diffuse idiopathic skeletal hyperostosis is associated with incident stroke in patients with increased cardiovascular risk

OBJECTIVES: Earlier retrospective studies have suggested a relation between DISH and cardiovascular disease, including myocardial infarction. The present study assessed the association between DISH and incidence of cardiovascular events and mortality in patients with high cardiovascular risk. METHODS: In this prospective cohort study, we included 4624 patients (mean age 58.4 years, 69.6% male) from the Second Manifestations of ARTerial disease cohort. The main end point was major cardiovascular events (MACE: stroke, myocardial infarction and vascular death). Secondary endpoints included all-cause mortality and separate vascular events. Cause-specific proportional hazard models were used to evaluate the risk of DISH on all outcomes, and subdistribution hazard models were used to evaluate the effect of DISH on the cumulative incidence. All models were adjusted for age, sex, body mass index, blood pressure, diabetes, non-HDL cholesterol, packyears, renal function and C-reactive protein. RESULTS: DISH was present in 435 (9.4%) patients. After a median follow-up of 8.7 (IQR 5.0–12.0) years, 864 patients had died and 728 patients developed a MACE event. DISH was associated with an increased cumulative incidence of ischaemic stroke. After adjustment in cause-specific modelling, DISH remained significantly associated with ischaemic stroke (HR 1.55; 95% CI: 1.01, 2.38), but not with MACE (HR 0.99; 95% CI: 0.79, 1.24), myocardial infarction (HR 0.88; 95% CI: 0.59, 1.31), vascular death (HR 0.94; 95% CI: 0.68, 1.27) or all-cause mortality (HR 0.94; 95% CI: 0.77, 1.16). CONCLUSIONS: The presence of DISH is independently associated with an increased incidence and risk for ischaemic stroke, but not with MACE, myocardial infarction, vascular death or all-cause mortality