1,721,211 research outputs found
Non-invasive vascular measures as prognostic predictors for older patients with non-ST elevation acute coronary syndrome
No full textBackgroundAdverse cardiac events are common in older patients with non-ST elevation acute coronary syndrome (NSTEACS), yet prognostic predictors are still lacking. This study investigated the long-term prognostic significance of non-invasive measures including endothelial function, carotid intima-media thickness (CIMT), and vascular stiffness in older NSTEACS patients referred for invasive treatment.MethodsNSTEACS patients aged 75 years and older recruited to a multicentre cohort study (NCT01933581) were assessed for baseline endothelial function using endoPAT logarithm of reactive hyperemia index (LnRHI), CIMT using B-mode ultrasound, and vascular stiffness using carotid-femoral pulse wave velocity (cfPWV). Long-term outcomes included major adverse cardiovascular events (MACE), a composite of death, reinfarction, urgent revascularization, stroke/transient ischemic attack, and significant bleeding.ResultsRecruitment resulted in 214 patients assessed for LnRHI, 190 patients assessed for CIMT and 245 patients assessed for cfPWV. For LnRHI group (median follow-up 4.73 years [IQR: 1.41-5.00]), Cox regression analysis revealed a trend towards increased risk of MACE (HR: 1.24 [95% CI: 0.80-1.93]; P = 0.328) and mortality (HR: 1.49 [95% CI: 0.86-2.59]; P = 0.157), but no significance was reached. No difference for other components of MACE was found. For CIMT group (median follow up 4.74 years [IQR: 1.55-5.00]), no statistically significant difference in MACE was found (HR: 0.92 [95% CI: 0.53-1.59]; P = 0.754). Similarly, for cfPWV group (median follow-up 4.96 years [IQR: 1.55-5.00]), results did not support prognostic significance (for MACE, HR: 0.95 [95% CI: 0.65-1.39]; P = 0.794).ConclusionEndothelial function, CIMT and vascular stiffness were proven unsuitable as strong prognostic predictors in older patients with NSTEACS.Clinical trial registration:NCT01933581
Imaging of atherosclerosis: study design and cardiovascular risk prediction
No full textCardiovascular disease is still the leading cause of morbidity and mortality worldwide.1 The majority of cardiovascular disease events is caused by atherosclerosis. Atherosclerosis is a slow and progressive disease of the arterial wall that is on the pathway between the effects of exposure to risk factors and the occurrence of cardiovascular events.2 Even though atherosclerosis may remain clinically silent for decades, it can be non-invasively assessed from early to late stages of the disease process using different imaging techniques. B-mode ultrasound is one of those imaging techniques which is frequently used to assess atherosclerosis in a safe, inexpensive, reliable, and reproducible manner. B-mode ultrasound measurements of the carotid intima-media thickness (CIMT) is an accepted measure of atherosclerosis that has frequently been used in observational studies to study the causes and consequences of atherosclerosis. In addition, numerous randomized controlled trials have used CIMT as alternative endpoint for cardiovascular disease events to evaluate the effects of new interventions. The main advantage of using CIMT as an outcome variable in studies is the considerable increase in efficacy in sample size and duration of follow-up when compared to studies using morbidity and mortality as primary outcome. Nevertheless, while CIMT measurements are increasingly being used, there are still no accepted standards on the use of CIMT measurements in various research areas. Hence, choices in the design and analysis of a CIMT study are generally based on experience and expert opinion rather than on solid evidence. Even though some methodological issues have begun to be addressed, there are many outstanding topics that need to be further evaluated. Also, there is a need to further explore alternative B-mode ultrasound approaches to examine the effects of new interventions on atherosclerosis. In addition, there is growing interest in the use of imaging of atherosclerosis as tool to improve risk prediction for cardiovascular disease in clinical practice. Yet, there is no conclusive evidence on the use of imaging of atherosclerosis in clinical practice and the added value of imaging of atherosclerosis in risk prediction for cardiovascular events. The aim of this thesis is threefold. First, several outstanding topics in the design and analytical phase of a CIMT trial will be addressed. The results from these studies will provide evidence for the most optimal approach to design and statistically analyze a CIMT study into the early effects of a new intervention on atherosclerosis before the start of a large morbidity and mortality study. In the second part, some alternative measures of atherosclerosis are evaluated with respect to their usefulness to study the effect of drug therapy on atherosclerosis. Finally, the role of imaging of atherosclerosis in risk prediction for cardiovascular disease in the general population will be examined
Non-invasive imaging of atherosclerosis in the young
No full textPrevention of cardiovascular disease (CVD) remains a top priority for public healthcare and healthcare professionals worldwide. In order to achieve this more knowledge on the major cause of CVD, atherosclerosis, is warranted. This thesis studied the pathophysiology of atherosclerosis in young individuals by further unraveling factors that are related to the atherosclerotic process in early life and examined the value of non-invasive imaging markers for atherosclerosis evaluation in the young. This information may be of help to improve identification of young individuals who are at high risk for developing symptomatic CVD later in life. As such, this thesis examined the relation of circulating inflammatory biomarkers and cardiovascular (CV) risk factors with various B-mode ultrasound and Magnetic Resonance Imaging (MRI)-derived imaging markers for atherosclerosis in healthy, young children, adolescents and young adults. This thesis concluded that, in addition to ultrasound-derived parameters of the structure of the arterial wall, ultrasound-derived composition of the arterial wall as well as MRI-derived aortic wall area, thickness and pulse wave velocity are valuable tools for mapping of atherosclerosis in young individuals. Especially MRI is a promising modality that will probably rise to become one of the most important tools to detect, evaluate and monitor atherosclerosis in young individuals. As such, MRI might play a role in therapeutic and preventive strategies in young individuals who are at high-risk for developing cardiovascular disease. In addition, this thesis demonstrated that various inflammatory cells appear to be involved in the development and progression of atherosclerosis in young individuals. As such, these cells might be of use to identify, treat and monitor young individuals who are at high-risk for developing clinically manifest CVD. Future research on this matter will hopefully result in an increase in CVD prevention by early identification and treatment of individuals who are at high-risk for developing clinically manifest CVD and as such, reduce the enormous impact that CVD currently has on our global healthcare, economy and society
Risk recognition in patients with atherosclerotic disease: associations of circulating biomarkers with plaque composition and clinical outcomes
No full textOver the last decade, the major underlying culprit of CVD; the atherosclerotic plaque, has shown a strong stabilization over time. Vulnerable plaque features such as large lipid core, intraplaque hemorrhage, and high macrophage content strongly decreased over time. Together with drops in inflammatory biomarkers it appears that two main drivers of atherosclerotic disease, lipids and inflammation, are now somewhat silenced. In first-world countries the current decline in major manifestation of CVD such as stroke and myocardial infarction is expected to be attributable to this stabilization. Rigorous lipid and blood pressure control, government legislation such as a public smoking ban and dietary reductions of salt and trans fats are likely causing these effects. We studied if these time-dependent effect help decrease secondary cardiovascular event-rate in a cohort of patients undergoing carotid endarterectomy. We did not find the health benefits as anticipated on. Secondary event rate remained high at approximately twenty-five percent during three-year follow-up and warrants our full efforts for future reduction. A possible explanation for this lack of decline could be that in these patients atherosclerotic disease burden is already too advanced and therefore less amenable for treatment. In patients affected by iliofemoral stenosis, secondary cardiovascular event-rate decreased over time but only due to a decrease in peripheral interventions. In patients with diabetes event-rate remained high and unchanged. In order to understand this risk for secondary cardiovascular events we studied several circulating biomarkers and their link with atherosclerotic disease. We show that decreased kidney function is a strong prognostic factor for the occurrence of secondary cardiovascular events and which specific plaque features associate with decreased kidney function in CEA patients. Interestingly we could not correlate decreased kidney function with abundant inflammation in the plaque, while inflammation is the proposed mediator for kidney-vasculature interaction. However, we did find a correlation with intraplaque hemorrhage and coagulation pathways indicating that perhaps coagulation is involved in plaque vulnerability and poor outcome in patients with decreased kidney function. Moreover, we studied the role of two major sex hormones, testosterone and estradiol, and their role in male patients undergoing carotid endarterectomy. We show that although the individual levels have limited prognostic value, the testosterone to estradiol ratio (T/E2) is more promising. Patients with low T/E2 had a higher risk of major cardiovascular events after CEA and showed increased inflammation in both plaque and blood. Lastly we focused on an often reported hematological parameter, the red cell distribution width (RDW), and its prognostic role in patients undergoing major cardiovascular surgery. There we show that this marker of anisocytosis is a strong predictor for inflammatory events following cardiovascular surgery. Moreover, we provide insight in hematopoietic tissue activity and their association with the RDW. We show a strong correlation of RDW with organ activity of the spleen and bone marrow and thereby likely reflecting a state of low grade inflammation
Cardiovascular disease in men and women: Different but Equal
No full textCardiovascular disease has long been called a “man’s disease. Women have long been underrepresented in cardiovascular clinical trials and a lack of sex-specific data has meant that we now lack evidence based guidance as to how appropriately manage and guide women with risk factors for CVD or CVD itself. This is important as specific cardiovascular diseases impact men and women differentially. For example women presenting with chest pain are more likely to be diagnosed with microvascular coronary artery disease than men presenting with chest pain and women are twice as likely to suffer from the most common heart failure sub-type; heart failure with preserved ejection fraction. Thus, the underlying pathophysiology of these diseases are currently not completely understood and we lack definitive treatment for these diseases. Therefore the aim of this thesis is therefore to help bridge gaps in knowledge of the influence of sex upon cardiovascular disease focusing on the two most common forms of cardiovascular disease: atherosclerosis and heart failure. This thesis underscores the cardinal sex differences (and similarities) in cardiovascular disease and emphasizes the importance of taking a sex-specific approach to cardiovascular research and clinical management
Early changes in heart failure with preserved ejection fraction: The merit of a sex-specific approach
Full text linkMore women than men have heart failure with preserved ejection fraction, but it is unclear why. This intriguing question is at the heart of this dissertation, where we explore the early changes that may lead to HFpEF, a condition that severely impacts quality of life. Unlike other forms of heart failure, HFpEF is not caused by a weakened ability of the heart to contract, but rather by its inability to relax properly. This issue of insufficient relaxation becomes more common with age, yet only a fraction of those affected, primarily wome, go on to develop heart failure symptoms. We are trying to better understand this from different perspectives. A key component of this dissertation is the HELPFulUP study, in which we follow patients with insufficient relaxation of the heart muscle over time. We make some interesting observations: In this population, women indeed develop heart failure more often than men. Surprisingly, though, the markers indicating poor relaxation of the heart muscle do not show significant changes over time. We do observe that reduced kidney function and increased blood pressure contribute to worsening over time in both men and women. Furthermore, this dissertation includes several chapters in which we examine biomarkers to better understand the underlying mechanism of reduced relaxation. For example, we discover that the protein called interferon-alpha 5 only plays a role in early changes that can lead to heart failure in women. We believe this is due to genetic differences between men and women. Additionally, we study a signal on the electrocardiogram called the TQ interval. The TQ interval correlates with the relaxation phase within a heartbeat. We observe that, as expected, the TQ interval is shorter in women than in men, and that there is a relationship with reduced heart relaxation and heart failure. This dissertation contains important new results from repeated measurements of heart relaxation and the progression to heart failure. Various underlying mechanisms are investigated through biomarker research
Sex matters to the arteries: studies into the (epi)genetic background and clinical outcome of atherosclerotic disease in women and men
No full textThe higher incidence of atherosclerotic disease at a younger age in men has directed most cardiovascular research since the early 1980s towards men. Yet, if studied, sex-differences are found in etiology, diagnostics, therapy and prognosis of CVD. It has been suggested that sex hormone status explains the differences between men and women and their progression to CVD. Moreover, sex chromosomes are beginning to be recognized as important players in sex differences in disease development, independent of sex hormones. This thesis describes studies into genetics and epigenetics of the atherosclerotic plaque, its histological characteristics and clinical outcome of atherosclerotic disease, mainly focusing on sex-differences. In most studies, atherosclerotic plaques from the Athero-Express Biobank, a biobank consisting of atherosclerotic plaque specimens of around 2300 carotid and 1000 (ilio)femoral arteries were used. A positive association was found between estradiol, the most abundant female sex-hormone, and the amount of intraplaque microvessels and macrophages. Female plaques generally display features that are associated with stable plaque characteristics, such as a large amount of collagen and smooth muscle cells. Although preliminary, these findings could thus point towards a more complex pathophysiological mechanism of the plaque erosion that is often observed in young women. Genetic variation on the Y chromosome (haplogroups) and its association with characteristics of the atherosclerotic plaque and aneurysmal artery wall was studied. No association was found, nor a different distribution of the haplogroups in these cohorts when compared with a Dutch cohort from the general population. The results make (causal) involvement of the Y chromosome in atherosclerotic disease less likely. However, an association was found between Y chromosomal loss and secondary cardiovascular events during 3-year follow-up. How Y chromosomal loss affects the development of cardiovascular events remains elusive. Across the genome, many sex-differences were identified in DNA methylation of the atherosclerotic plaque and it was observed that most of them were not associated with atherosclerotic disease risk factors or characteristics of the atherosclerotic plaque. Not many DNA methylation studies investigated diseased tissue. These findings emphasize the need for stratification by sex in epigenetic studies. Mortality rates after coronary artery bypass grafting surgery between women and men were studied in the IMAGINE trial. A poorer survival for women in univariable analysis, but not in multivariable analysis, was observed. This effect has been observed also in other coronary artery bypass grafting cohorts and warrants further study, preferably in a much larger number of women. When studying long-term follow-up of both carotid and femoral endarterectomy in the Athero-Express Biobank, sex-differences were observed in survival after carotid endarterectomy surgery, where women displayed an advantage over men and followed the survival curve of the cohort of age-matched women from the general population. However, such a sex-difference was not observed after femoral endarterectomy surgery. Other studies within this thesis include the identification of novel candidate genes using 4C-sequencing of cardiovascular disease associated genetic loci, a review on the poor translatability of murine atherosclerosis genes to humans and time-dependent changes and associations with diabetes mellitus in ilio-femoral atherosclerotic plaque composition
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