The FReedom from Ischemic Events - New Dimensions for Survival (FRIENDS) registry: design of a prospective cohort study of patients with advanced peripheral artery disease

Background: Advanced lower extremity peripheral artery disease (PAD), whether presenting as acute limb ischemia (ALI) or chronic critical limb ischemia (CLI), is associated with high rates of cardiovascular ischemic events, amputation, and death. Past research has focused on strategies of revascularization, but few data are available that prospectively evaluate the impact of key process of care factors (spanning pre-admission, acute hospitalization, and post-discharge) that might contribute to improving short and long-term health outcomes. Methods/Design The FRIENDS registry is designed to prospectively evaluate a range of patient and health system care delivery factors that might serve as future targets for efforts to improve limb and systemic outcomes for patients with ALI or CLI. This hypothesis-driven registry was designed to evaluate the contributions of: (i) pre-hospital limb ischemia symptom duration, (ii) use of leg revascularization strategies, and (iii) use of risk-reduction pharmacotherapies, as pre-specified factors that may affect amputation-free survival. Sequential patients would be included at an index “vascular specialist-defined” ALI or CLI episode, and patients excluded only for non-vascular etiologies of limb threat. Data including baseline demographics, functional status, co-morbidities, pre-hospital time segments, and use of medical therapies; hospital-based use of revascularization strategies, time segments, and pharmacotherapies; and rates of systemic ischemic events (e.g., myocardial infarction, stroke, hospitalization, and death) and limb ischemic events (e.g., hospitalization for revascularization or amputation) will be recorded during a minimum of one year follow-up. Discussion The FRIENDS registry is designed to evaluate the potential impact of key factors that may contribute to adverse outcomes for patients with ALI or CLI. Definition of new “health system-based” therapeutic targets could then become the focus of future interventional clinical trials for individuals with advanced PAD

Low Serum Glutathione Peroxidase Activity Is Associated with Increased Cardiovascular Mortality in Individuals with Low HDLc’s

Background Since oxidized LDL is thought to initiate atherosclerosis and the serum glutathione peroxidase (GPx3) reduces oxidized lipids, we investigated whether high GPx3 activity reduces cardiovascular disease (CVD) mortality. Methods We determined GPx3 in stored samples from the Minnesota Heart Survey of 130 participants who after 5 to 12 years of follow-up had died of CVD and 240 controls. Participants were 26 to 85 years old and predominantly white. In a nested case-control, study we performed logistic regressions to calculate odds ratios (OR) adjusted for age, sex, baseline year, body mass index, smoking, alcohol intake, physical activity, total and HDL cholesterols, systolic blood pressure, serum glucose and gamma glutamyltransferase (GTT) activity. The referent was the quartile with the highest GPx3 activity (quartile 4). Results OR’s for CVD mortality for increasing quartiles of GPx3 were 2.37, 2.14, 1.83 and 1.00 (P for trend 0.02). This inverse correlation was confined to those with HDLc’s below the median (P for interaction, 0.006). The OR’s for increasing quartiles of GPx3 in this group were 6.08, 5.00, 3.64 and 1.00 (P for trend, 0.002). Conclusions Individuals with both low HDLc and GPx3 activity are at markedly increased risk for death from CVD

Air pollution and cardiovascular disease: A Statement for Healthcare Professionals From the Expert Panel on Population and Prevention Science of the American Heart Association

Air pollution is a heterogeneous, complex mixture of gases, liquids, and particulate matter. Epidemiological studies have demonstrated a consistent increased risk for cardiovascular events in relation to both short- and long-term exposure to present-day concentrations of ambient particulate matter. Several plausible mechanistic pathways have been described, including enhanced coagulation/thrombosis, a propensity for arrhythmias, acute arterial vasoconstriction, systemic inflammatory responses, and the chronic promotion of atherosclerosis. The purpose of this statement is to provide healthcare professionals and regulatory agencies with a comprehensive review of the literature on air pollution and cardiovascular disease. In addition, the implications of these findings in relation to public health and regulatory policies are addressed. Practical recommendations for healthcare providers and their patients are outlined. In the final section, suggestions for future research are made to address a number of remaining scientific questions

Particulate matter air pollution and cardiovascular disease: An update to the scientific statement from the American Heart Association

In 2004, the first American Heart Association scientific statement on “Air Pollution and Cardiovascular Disease” concluded that exposure to particulate matter (PM) air pollution contributes to cardiovascular morbidity and mortality. In the interim, numerous studies have expanded our understanding of this association and further elucidated the physiological and molecular mechanisms involved. The main objective of this updated American Heart Association scientific statement is to provide a comprehensive review of the new evidence linking PM exposure with cardiovascular disease, with a specific focus on highlighting the clinical implications for researchers and healthcare providers. The writing group also sought to provide expert consensus opinions on many aspects of the current state of science and updated suggestions for areas of future research. On the basis of the findings of this review, several new conclusions were reached, including the following: Exposure to PM less than 2.5 μm in diameter (PM2.5) over a few hours to weeks can trigger cardiovascular disease–related mortality and nonfatal events; longer-term exposure (eg, a few years) increases the risk for cardiovascular mortality to an even greater extent than exposures over a few days and reduces life expectancy within more highly exposed segments of the population by several months to a few years; reductions in PM levels are associated with decreases in cardiovascular mortality within a time frame as short as a few years; and many credible pathological mechanisms have been elucidated that lend biological plausibility to these findings. It is the opinion of the writing group that the overall evidence is consistent with a causal relationship between PM2.5 exposure and cardiovascular morbidity and mortality. This body of evidence has grown and been strengthened substantially since the first American Heart Association scientific statement was published. Finally, PM2.5 exposure is deemed a modifiable factor that contributes to cardiovascular morbidity and mortality

C-Reactive Protein (CRP) Gene Polymorphisms, CRP Levels, and Risk of Incident Coronary Heart Disease in Two Nested Case-Control Studies

Background: C-reactive protein (CRP), an acute phase reactant and marker of inflammation, has been shown to predict risk of incident cardiovascular events. However, few studies have comprehensively examined six common single-nucleotide polymorphisms (SNPs) in the CRP gene, haplotypes, and plasma CRP levels with risk of coronary heart disease (CHD). Methods and Findings: We conducted parallel nested case-control studies within two ongoing, prospective cohort studies of U.S. women (Nurses' Health Study) and men (Health Professionals Follow-up Study). Blood samples were available in a subset of 32,826 women and 18,225 men for biomarker and DNA analyses. During 8 and 6 years of follow-up, 249 women and 266 men developed incident nonfatal myocardial infarction or fatal CHD, and controls (498 women, 531 men) were matched 2:1 on age, smoking, and date of blood draw from participants free of cardiovascular disease at the time the case was diagnosed. Among both women and men, minor alleles were significantly associated with higher CRP levels for SNPs 1919A greater than T and 4741G greater than C, but associated with lower CRP levels for SNPs 2667G greater than C and 3872C greater than T. SNP 2667G greater than C was individually associated with increased risk of CHD in both women [OR 1.57 (95% CI 1.01–2.44); p = 0.047] and men [1.93 (95% CI 1.30–2.88); p = 0.001]. Two of the five common haplotypes were associated with lower CRP levels, and Haplotype 4 which included minor alleles for 2667 and 3872 was associated with significantly lower CRP levels and an elevated risk of CHD. The remaining SNPs or haplotypes were not associated with CHD in both populations. Conclusions: Common variation in the CRP gene was significantly associated with plasma CRP levels; however, the association between common SNPs and CRP levels did not correspond to a predicted change in CHD risk. The underlying inflammatory processes which predict coronary events cannot be captured solely by variation in the CRP gene

Third universal definition of myocardial infarction

"Myocardial infarction (MI) can be recognised by clinical features, including electrocardiographic (ECG) findings, elevated values of biochemical markers (biomarkers) of myocardial necrosis, and by imaging, or may be defined by pathology. It is a major cause of death and disability worldwide. MI may be the first manifestation of coronary artery disease (CAD) or it may occur, repeatedly, in patients with established disease. Information on MI rates can provide useful information regarding the burden of CAD within and across populations, especially if standardized data are collected in a manner that distinguishes between incident and recurrent events. From the epidemiological point of view, the incidence of MI in a population can be used as a proxy for the prevalence of CAD in that population. The term ‘myocardial infarction’ may have major psychological and legal implications for the individual and society. It is an indicator of one of the leading health problems in the world and it is an outcome measure in clinical trials, observational studies and quality assurance programmes. These studies and programmes require a precise and consistent definition of MI. In the past, a general consensus existed for the clinical syndrome designated as MI. In studies of disease prevalence, the World Health Organization (WHO) defined MI from symptoms, ECG abnormalities and cardiac enzymes. However, the development of ever more sensitive and myocardial tissue-specific cardiac biomarkers and more sensitive imaging techniques now allows for detection of very small amounts of myocardial injury or necrosis. Additionally, the management of patients with MI has significantly improved, resulting in less myocardial injury and necrosis, in spite of a similar clinical presentation. Moreover, it appears necessary to distinguish the various conditions which may cause MI, such as ‘spontaneous’ and ‘procedure-related’ MI. Accordingly, physicians, other healthcare providers and patients require an up-to-date definition of MI.