Effect of exercise after a deep venous thrombosis: A systematic review.

Post-thrombotic syndrome (PTS) is a common complication after deep vein thrombosis (DVT) and has a major impact on physical symptoms, quality of life (QoL) and economic costs. Relatively simple lifestyle interventions as physical exercise might reduce PTS severity and increase QoL. To evaluate the direct and long-term effects of physical activity in patients with an acute or previous DVT. We conducted a systematic review through an additional search from 2007 up to March 2022, to complement the comprehensive systematic review of Kahn et al. Articles evaluating the effect of exercise after a DVT including symptoms, QoL and the incidence and severity of PTS, were included. Quality of the studies was assessed using a GRADE-like checklist and results were reported according to the PRISMA Statement. Ten studies were included, seven randomized controlled trials and three cohort studies. We identified three types of physical activity based on timing and duration; (1) early mobilisation in the acute phase of the DVT; (2) short duration exercise 1 year after DVT and (3) prolonged exercise during follow-up after a previous DVT. Early mobilisation showed improvement in QoL and pain reduction and after 2 years it resulted in a significant reduction of PTS severity. Prolonged supervised exercise resulted in improvement of QoL. In addition, positive effects on symptoms of venous insufficiency and muscle functions were observed. None of the included studies reported an increased risk of PTS or worsening of symptoms due to physical activity. Physical exercise after a DVT is safe, improves QoL, reduces pain and decreases PTS severity. Lifestyle intervention such as guided individualized training programs can be a useful supplementary therapy for patients after a DVT or for PTS patients. Optimal training programs may be identified by further studies that improve patient-oriented outcomes for both adults and children after a DVT.

Visceral aneurysms: Old paradigms, new insights?

True visceral artery aneurysms (VAAs) are a rare entity with an incidence of 0.01-2%. The risk of rupture varies amongst the different types of VAAs and is higher for pseudo aneurysms compared with true aneurysms. Size, growth, symptoms, underlying disease, pregnancy and liver transplantation have all been associated with increased risk of rupture. Mortality rates after rupture are around 25%. The splenic artery is most commonly affected and the etiology is predominantly atherosclerosis. Open repair can be done by simple ligation or reconstruction of the artery, while endovascular options include embolization or using a stent graft. Location, collateral circulation and medical condition of the patient should all be taken into account when an intervention is planned. We compared types of treatment and searched for risk factors for rupture but unfortunately, the level of evidence found in the literature is low. Therefore, deciding when and how to treat a patient with a VAA based on the current literature, remains challenging for clinicians.

Polymorphisms of the renin-angiotensin system are associated with blood pressure, atherosclerosis and cerebral white matter pathology.

BACKGROUND: The renin-angiotensin system is involved in the development of hypertension, atherosclerosis and cardiovascular disease. We studied the association between the M235T polymorphism of the angiotensinogen gene (AGT) and the C573T polymorphism of the angiotensin II type 1 receptor (AT1R) and blood pressure, carotid atherosclerosis and cerebrovascular disease. METHODS: We genotyped over 6000 subjects from the Rotterdam Study and more than 1000 subjects from the Rotterdam Scan Study. We used logistic regression and univariate analyses, adjusting for age and sex with, for AGT, the MM and, for AT1R, the TT genotype as reference. RESULTS: We found that AGT-235T increased systolic (p for trend = 0.03) and diastolic blood pressure (p for trend = 0.04). The prevalence of carotid plaques was increased 1.25-fold (95% CI 1.02-1.52) in AGT-TT carriers. There was a significant increase in mean volume deep subcortical white matter lesions (WML) for AGT-TT carriers (1.78 ml vs 1.09 ml in the reference group; p = 0.008). A significant interaction was found between AGT and AT1R, further increasing the effect on periventricular and subtotal WML (p for interaction = 0.02). We found a non-significant increased risk of silent brain infarction for AGT-TT carriers and AT1R-CC carriers, but no effect on stroke. CONCLUSION: We found an association between AGT and blood pressure, atherosclerosis and WML. Also, we found synergistic effects between AGT and AT1R on the development of WML. These findings raise the question of whether the renin-angiotensin system may be a therapeutic target for the prevention of cerebral white matter pathology.

Cerebrovascular risk factors do not contribute to genetic variance of cognitive function: the ERF study.

Impaired cognition in later life may result from Alzheimer's disease-related pathology, but also from vascular pathology. We studied to what extent vascular risk explained heritability of cognition in 780 individuals, related in one extended pedigree in a genetically isolated population, in the ERF study. Heritability was estimated using variance components modelling (SOLAR). Univariate analyses included models with and without vascular disease; bivariate analyses included both cognitive and vascular traits, such as blood pressure, serum glucose or lipids. Heritability for immediate and delayed recall, recognition, semantic fluency, Trail making B and Stroop tests was significant, with estimates from 0.16 to 0.36. Vascular factors did not affect cognitive functions, except immediate recall and the Stroop test. Heritability estimates did not change significantly when adjusted for vascular disease. We found no genetic correlation between cognition and vascular traits. Therefore, in this population vascular disease is mildly associated with cognitive dysfunction, and in those with vascular disease, the underlying genetic risk factors are not likely to account for the genetic variation in cognition at adult age.

Insulin-like growth factor I promoter polymorphism, risk of stroke, and survival after stroke: the Rotterdam study.

BACKGROUND AND PURPOSE: Low levels of insulin-like growth factor I (IGF-I) predispose to atherosclerosis and may therefore increase the risk of stroke. Low levels have also been found to influence the outcome of cardiovascular and cerebrovascular disease. A polymorphism in the promoter region of the IGF-I gene influences IGF-I levels. Non-carriers of the 192 bp allele have lower levels of IGF-I compared with 192 bp allele carriers. We studied the IGF-I polymorphism in relation to the risk of stroke and survival after stroke. METHODS: We studied 6808 subjects of the Rotterdam Study, who were followed for the occurrence of stroke and death after stroke. Subjects were grouped according to the 192 bp allele of IGF-I into non-carriers, heterozygotes, and homozygotes. The risk of stroke and survival after stroke was studied using Cox regression analysis, adjusting for age and sex, with homozygotes for the wildtype allele as the reference. RESULTS: Non-carriers had a relative risk of 0.8 (95% CI: 0.6 to 1.0) for the occurrence of any stroke and 0.7 (95% CI: 0.5 to 1.0) for ischaemic stroke. For non-carriers, the relative risk of death after any stroke was 1.5 (95% CI: 1.0 to 2.2). After an ischaemic stroke, this relative risk was 1.5 (95% CI: 0.9 to 2.6) and after a haemorrhagic stroke 5.2 (95% CI: 1.3 to 21.5). CONCLUSIONS: Our study suggests that IGF-I is a significant determinant of survival after stroke.

Heritability of the function and structure of the arterial wall: findings of the Erasmus Rucphen Family (ERF) study.

BACKGROUND AND PURPOSE: Using 930 individuals connected in a single pedigree from an isolated population, participants of the Erasmus Rucphen Family (ERF) study, we investigated the heritability of carotid-femoral pulse wave velocity (PWV), carotid intima media thickness (IMT), and carotid plaque score. METHODS: PWV was measured between the carotid and femoral arteries as an indicator of aortic stiffness. Common carotid IMT and plaque score, quantifying alterations in arterial wall structure, were measured by ultrasonography. RESULTS: All 3 traits were significantly associated with classic cardiovascular risk factors. Age- and gender-adjusted heritability estimates were 0.36 for PWV, 0.41 for carotid IMT, and 0.28 for plaque score. After adjustment for appropriate risk factors, the heritabilities were 0.26, 0.35, and 0.21 for PWV, IMT, and plaque score, respectively. All heritability estimates were statistically significant (P<0.001). Taking into account different proportions of variance associated with covariates for each trait, genetic factors explained &12% of the total variability for each of the phenotypes. CONCLUSIONS: To our knowledge, this is the first report on the heritability of PWV. The heritability estimates of IMT and plaque score were similar to those in previous reports. We conclude that genetic factors significantly contribute to arterial structure and function in this isolated population, presenting the opportunity to locate susceptibility genes related to cardiovascular disorders.

Familial aggregation, the PDE4D gene, and ischemic stroke in a genetically isolated population.

OBJECTIVE: The purpose of this investigation was to study the familial aggregation of ischemic stroke and the association between the PDE4D gene and ischemic stroke. METHODS: The study was performed in an isolated population in The Netherlands, where the authors identified 91 patients with ischemic stroke. Ischemic stroke was subclassified in large- and small-vessel infarction. The authors calculated kinship and inbreeding coefficients and genotyped all patients for three single-nucleotide polymorphisms (SNPs) in the PDE4D gene. RESULTS: The proportion of related pairs was higher in patients with ischemic stroke (68.8%) compared with controls (30.7%; p < 0.001). For large-vessel infarction, the proportion of related pairs was higher (71%) compared with small-vessel infarction (62.8%; p < 0.001). Familial aggregation was strongest for patients with early onset (age at onset < 45 years). All stroke groups were significantly more inbred compared with controls. In inbred individuals, the C allele of SNP45 increased the risk of small-vessel infarction 4.8 times (95% CI 1.1 to 22.3) compared with controls (p = 0.04). The T allele of SNP39 increased the risk of small-vessel infarction 6.3 times (95% CI 1.4 to 28.7) compared with controls (p = 0.02). No associations were found for large-vessel stroke. CONCLUSIONS: There was familial aggregation of ischemic stroke and a difference in degree of familial clustering between stroke subtypes. The authors also found that the PDE4D gene is significantly associated with small-vessel infarction in inbred individuals.

Impact of genetic testing on complex diseases.

OBJECTIVE: Wide applications for genetic testing in the clinical care of complex diseases have been discussed. However, it has never been quantified to what extent genetic testing could eventually be useful in the clinical care of common disorders. We aimed to quantify the theoretically possible utilization in common ischemic stroke, an example of a complex disease. METHODS: We computed the possible impact of genetic testing on risk assessment, secondary prevention and prognosis of ischemic stroke. This was done for hypothetical genotypes with different frequencies and effects. RESULTS: To apply pharmacogenetic secondary prevention based on a genotype with a frequency of 10% and 33% risk reduction, 204 subjects would have to be screened and 110 given genotype specific treatment for 1 year, in order to prevent one recurrent stroke, compared with standard therapy. The application of genetic testing seems to be less promising in risk assessment and the assessment of prognosis of common ischemic stroke. CONCLUSIONS: The highest impact of genetic testing on clinical practice of stroke will be in the areas of secondary prevention. Given the weak effects of reported susceptibility genotypes, it is theoretically unlikely that genetic screening will be used for the assessment of risk or prognosis of a complex disorder, except for Mendelian types of disease.