Patients with acute coronary syndrome (ACS) and concomitant noncoronary atherosclerosis have a high risk of major adverse cardiovascular events (MACEs) and death. The impact of lipid lowering by ...proprotein convertase subtilisin-kexin type 9 inhibition in such patients is undetermined.
This pre-specified analysis from ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) determined whether polyvascular disease influenced risks of MACEs and death and their modification by alirocumab in patients with recent ACS and dyslipidemia despite intensive statin therapy.
Patients were randomized to alirocumab or placebo 1 to 12 months after ACS. The primary MACEs endpoint was the composite of coronary heart disease death, nonfatal myocardial infarction, fatal or nonfatal ischemic stroke, or unstable angina requiring hospitalization. All-cause death was a secondary endpoint.
Median follow-up was 2.8 years. Of 18,924 patients, 17,370 had monovascular (coronary) disease, 1,405 had polyvascular disease in 2 beds (coronary and peripheral artery or cerebrovascular), and 149 had polyvascular disease in 3 beds (coronary, peripheral artery, cerebrovascular). With placebo, the incidence of MACEs by respective vascular categories was 10.0%, 22.2%, and 39.7%. With alirocumab, the corresponding absolute risk reduction was 1.4% (95% confidence interval CI: 0.6% to 2.3%), 1.9% (95% CI: -2.4% to 6.2%), and 13.0% (95% CI: -2.0% to 28.0%). With placebo, the incidence of death by respective vascular categories was 3.5%, 10.0%, and 21.8%; the absolute risk reduction with alirocumab was 0.4% (95% CI: -0.1% to 1.0%), 1.3% (95% CI: -1.8% to 4.3%), and 16.2% (95% CI: 5.5% to 26.8%).
In patients with recent ACS and dyslipidemia despite intensive statin therapy, polyvascular disease is associated with high risks of MACEs and death. The large absolute reductions in those risks with alirocumab are a potential benefit for these patients. (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab ODYSSEY OUTCOMES: NCT01663402).
Spontaneous coronary artery dissection (SCAD) is an increasingly recognized cause of acute coronary syndromes (ACS) afflicting predominantly younger to middle-aged women. Observational studies have ...reported a high prevalence of extracoronary vascular anomalies, especially fibromuscular dysplasia (FMD) and a low prevalence of coincidental cases of atherosclerosis. PHACTR1/EDN1 is a genetic risk locus for several vascular diseases, including FMD and coronary artery disease, with the putative causal noncoding variant at the rs9349379 locus acting as a potential enhancer for the endothelin-1 (EDN1) gene.
This study sought to test the association between the rs9349379 genotype and SCAD.
Results from case control studies from France, United Kingdom, United States, and Australia were analyzed to test the association with SCAD risk, including age at first event, pregnancy-associated SCAD (P-SCAD), and recurrent SCAD.
The previously reported risk allele for FMD (rs9349379-A) was associated with a higher risk of SCAD in all studies. In a meta-analysis of 1,055 SCAD patients and 7,190 controls, the odds ratio (OR) was 1.67 (95% confidence interval CI: 1.50 to 1.86) per copy of rs9349379-A. In a subset of 491 SCAD patients, the OR estimate was found to be higher for the association with SCAD in patients without FMD (OR: 1.89; 95% CI: 1.53 to 2.33) than in SCAD cases with FMD (OR: 1.60; 95% CI: 1.28 to 1.99). There was no effect of genotype on age at first event, P-SCAD, or recurrence.
The first genetic risk factor for SCAD was identified in the largest study conducted to date for this condition. This genetic link may contribute to the clinical overlap between SCAD and FMD.
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Aims
There is limited evidence regarding the association between physical activity and vascular complications, particularly microvascular disease, in patients with type 2 diabetes.
Methods
From the ...11 140 patients in the ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron modified release Controlled Evaluation) trial, the effect of physical activity, categorized as none, mild, moderate or vigorous, and the number of sessions within a week, was examined in multivariable regression models adjusted for potential confounders. The study end‐points were major cardiovascular events, microvascular complications and all‐cause mortality.
Results
Forty‐six percent of participants reported undertaking moderate to vigorous physical activity for >15 min at least once in the previous week. During a median of 5 years of follow‐up, 1031 patients died, 1147 experienced a major cardiovascular event and 1136 a microvascular event. Compared to patients who undertook no or mild physical activity, those reporting moderate to vigorous activity had a decreased risk of cardiovascular events (HR: 0.78, 95% CI: 0.69–0.88, p < 0.0001), microvascular events (HR: 0.85, 95% CI: 0.76–0.96, p = 0.010) and all‐cause mortality (HR: 0.83, 95% CI: 0.73–0.94, p = 0.0044).
Conclusions
Moderate to vigorous, but not mild, physical activity is associated with a reduced incidence of cardiovascular events, microvascular complications and all‐cause mortality in patients with type 2 diabetes.
Coronary-artery dissections account for less than 1% of acute myocardial infarctions, occur most commonly in women and most often between the ages of 47 and 53 years, may be associated with an ...underlying disorder such as fibromuscular dysplasia and other noncoronary arterial abnormalities, and are usually treated medically.
The prevalence of diabetes mellitus will likely increase globally from 371 million individuals in 2013 to 552 million individuals in 2030. This epidemic is mainly attributable to type 2 diabetes ...mellitus (T2DM), which represents about 90-95% of all cases. Cardiovascular disease is the leading cause of mortality among individuals with diabetes mellitus, and >50% of patients will die from a cardiovascular event-especially coronary artery disease, but also stroke and peripheral vascular disease. Classic risk factors such as elevated levels of LDL cholesterol and blood pressure, as well as smoking, are risk factors for adverse cardiovascular events in patients with type 1 diabetes mellitus (T1DM) and T2DM to a similar degree as they are in healthy individuals. Patients with T1DM develop insulin resistance in the months after diabetes mellitus diagnosis, and patients with T2DM typically develop insulin resistance before hyperglycaemia occurs. Insulin resistance and hyperglycaemia, in turn, further increase the risk of adverse cardiovascular events. This Review discusses the mechanisms by which T1DM and T2DM can lead to cardiovascular disease and how these relate to the risk factors for coronary artery disease.
Sinusoidal obstruction syndrome or veno-occlusive disease (SOS/VOD) is a potentially life-threatening complication of hematopoietic SCT (HSCT). This review aims to highlight, on behalf of the ...European Society for Blood and Marrow Transplantation, the current knowledge on SOS/VOD pathophysiology, risk factors, diagnosis and treatments. Our perspectives on SOS/VOD are (i) to accurately identify its risk factors; (ii) to define new criteria for its diagnosis; (iii) to search for SOS/VOD biomarkers and (iv) to propose prospective studies evaluating SOS/VOD prevention and treatment in adults and children.
Abstract
This study tested the hypothesis that patients with PAD have impaired health-related quality of life (HRQoL) to a degree similar to that of patients with other types of cardiovascular ...disease (other-CVD), and also evaluated the clinical features of PAD associated with impaired HRQoL. This was a cross-sectional study in 350 primary care practice sites nationwide with 6,499 participants. The reference group had no clinical or hemodynamic evidence of PAD or other-CVD; the PAD group had an ankle-brachial index < 0.90 or a prior history of PAD; the other-CVD group had a clinical history of cardiac or cerebral vascular disease (but no PAD), and the combined PAD-other-CVD group included both diagnoses. Individuals were assessed using four HRQoL questionnaires including the Walking Impairment Questionnaire (WIQ), Medical Outcomes Study SF-36 (SF-36), Cantril Ladder of Life and the PAD Quality of Life questionnaire. PAD patients had lower WIQ distance scores than the other-CVD group. Both the PAD and other-CVD groups had significantly lower SF-36 Physical Function scores compared with the reference group. The WIQ revealed that PAD patients were more limited by calf pain, whereas other-CVD patients were more limited by chest pain, shortness of breath and palpitations. In conclusion, in this nationwide study, one of the first to directly compare the HRQoL burden of CVD with that of PAD, the evaluation of PAD in office practice revealed a HRQoL burden as great in magnitude as in patients with other forms of CVD.
Over the past decade, spontaneous coronary artery dissection (SCAD) has emerged as an important cause of myocardial infarction, particularly among younger women. The pace of knowledge acquisition has ...been rapid, but ongoing challenges include accurately diagnosing SCAD and improving outcomes. Many SCAD patients experience substantial post-SCAD symptoms, recurrent SCAD, and psychosocial distress. Considerable uncertainty remains about optimal management of associated conditions, risk stratification and prevention of complications, recommendations for physical activity, reproductive planning, and the role of genetic evaluations. This review provides a clinical update on the diagnosis and management of patients with SCAD, including pregnancy-associated SCAD and pregnancy after SCAD, and highlight high-priority knowledge gaps that must be addressed.
The cushioning function of large arteries encompasses distension during systole and recoil during diastole which transforms pulsatile flow into a steady flow in the microcirculation. Arterial ...stiffness, the inverse of distensibility, has been implicated in various etiologies of chronic common and monogenic cardiovascular diseases and is a major cause of morbidity and mortality globally. The first components that contribute to arterial stiffening are extracellular matrix (ECM) proteins that support the mechanical load, while the second important components are vascular smooth muscle cells (VSMCs), which not only regulate actomyosin interactions for contraction but mediate also mechanotransduction in cell-ECM homeostasis. Eventually, VSMC plasticity and signaling in both conductance and resistance arteries are highly relevant to the physiology of normal and early vascular aging. This review summarizes current concepts of central pressure and tensile pulsatile circumferential stress as key mechanical determinants of arterial wall remodeling, cell-ECM interactions depending mainly on the architecture of cytoskeletal proteins and focal adhesion, the large/small arteries cross-talk that gives rise to target organ damage, and inflammatory pathways leading to calcification or atherosclerosis. We further speculate on the contribution of cellular stiffness along the arterial tree to vascular wall stiffness. In addition, this review provides the latest advances in the identification of gene variants affecting arterial stiffening. Now that important hemodynamic and molecular mechanisms of arterial stiffness have been elucidated, and the complex interplay between ECM, cells, and sensors identified, further research should study their potential to halt or to reverse the development of arterial stiffness.
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