Although aortic stenosis is a common condition associated with major morbidity, mortality, and health economic costs, there are currently no medical interventions capable of delaying or halting its ...progression. Re-evaluation of the underlying pathophysiology is therefore required so that novel therapeutic strategies can be developed. Aortic stenosis is characterized by progressive aortic valve narrowing and secondary left ventricular hypertrophy. Both processes are important because in combination they drive the development of symptoms and adverse events that characterize the latter stages of the disease. In this review, the authors examine the pathophysiology of aortic stenosis with respect to both the valve and the myocardium. In particular, the authors focus on the role of inflammation, fibrosis, and calcification in progressive valve narrowing and then examine the development of left ventricular hypertrophy, its subsequent decompensation, and the transition to heart failure. Finally the authors discuss potential therapeutic strategies on the basis of similarities aortic stenosis shares with other pathological conditions.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
In a randomized trial, patients with chest pain underwent a standard diagnostic evaluation with or without coronary CT angiography (CTA). The group assigned to CTA had a lower rate of death from ...coronary heart disease or nonfatal myocardial infarction at 5 years.
Abstract Background In a prospective, multicenter, randomized controlled trial, 4,146 patients were randomized to receive standard care or standard care plus coronary computed tomography angiography ...(CCTA). Objectives The purpose of this study was to explore the consequences of CCTA-assisted diagnosis on invasive coronary angiography, preventive treatments, and clinical outcomes. Methods In post hoc analyses, we assessed changes in invasive coronary angiography, preventive treatments, and clinical outcomes using national electronic health records. Results Despite similar overall rates (409 vs. 401; p = 0.451), invasive angiography was less likely to demonstrate normal coronary arteries (20 vs. 56; hazard ratios HRs: 0.39 95% confidence interval (CI): 0.23 to 0.68; p < 0.001) but more likely to show obstructive coronary artery disease (283 vs. 230; HR: 1.29 95% CI: 1.08 to 1.55; p = 0.005) in those allocated to CCTA. More preventive therapies (283 vs. 74; HR: 4.03 95% CI: 3.12 to 5.20; p < 0.001) were initiated after CCTA, with each drug commencing at a median of 48 to 52 days after clinic attendance. From the median time for preventive therapy initiation (50 days), fatal and nonfatal myocardial infarction was halved in patients allocated to CCTA compared with those assigned to standard care (17 vs. 34; HR: 0.50 95% CI: 0.28 to 0.88; p = 0.020). Cumulative 6-month costs were slightly higher with CCTA: difference $462 (95% CI: $303 to $621). Conclusions In patients with suspected angina due to coronary heart disease, CCTA leads to more appropriate use of invasive angiography and alterations in preventive therapies that were associated with a halving of fatal and non-fatal myocardial infarction. (Scottish COmputed Tomography of the HEART Trial SCOT-HEART; NCT01149590 )
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Although the mechanisms are unknown, it has been suggested that transient exposure to traffic-derived air pollution may be a trigger for acute myocardial infarction. The study aim was to investigate ...the effects of diesel exhaust inhalation on vascular and endothelial function in humans.
In a double-blind, randomized, cross-over study, 30 healthy men were exposed to diluted diesel exhaust (300 microg/m3 particulate concentration) or air for 1 hour during intermittent exercise. Bilateral forearm blood flow and inflammatory factors were measured before and during unilateral intrabrachial bradykinin (100 to 1000 pmol/min), acetylcholine (5 to 20 microg/min), sodium nitroprusside (2 to 8 microg/min), and verapamil (10 to 100 microg/min) infusions 2 and 6 hours after exposure. There were no differences in resting forearm blood flow or inflammatory markers after exposure to diesel exhaust or air. Although there was a dose-dependent increase in blood flow with each vasodilator (P<0.0001 for all), this response was attenuated with bradykinin (P<0.05), acetylcholine (P<0.05), and sodium nitroprusside (P<0.001) infusions 2 hours after exposure to diesel exhaust, which persisted at 6 hours. Bradykinin caused a dose-dependent increase in plasma tissue plasminogen activator (P<0.0001) that was suppressed 6 hours after exposure to diesel (P<0.001; area under the curve decreased by 34%).
At levels encountered in an urban environment, inhalation of dilute diesel exhaust impairs 2 important and complementary aspects of vascular function in humans: the regulation of vascular tone and endogenous fibrinolysis. These important findings provide a potential mechanism that links air pollution to the pathogenesis of atherothrombosis and acute myocardial infarction.
Adverse cardiovascular effects of air pollution Mills, Nicholas L; Donaldson, Ken; Hadoke, Paddy W ...
Nature clinical practice cardiovascular medicine,
01/2009, Volume:
6, Issue:
1
Journal Article
Peer reviewed
Air pollution is increasingly recognized as an important and modifiable determinant of cardiovascular disease in urban communities. Acute exposure has been linked to a range of adverse cardiovascular ...events including hospital admissions with angina, myocardial infarction, and heart failure. Long-term exposure increases an individual's lifetime risk of death from coronary heart disease. The main arbiter of these adverse health effects seems to be combustion-derived nanoparticles that incorporate reactive organic and transition metal components. Inhalation of this particulate matter leads to pulmonary inflammation with secondary systemic effects or, after translocation from the lung into the circulation, to direct toxic cardiovascular effects. Through the induction of cellular oxidative stress and proinflammatory pathways, particulate matter augments the development and progression of atherosclerosis via detrimental effects on platelets, vascular tissue, and the myocardium. These effects seem to underpin the atherothrombotic consequences of acute and chronic exposure to air pollution. An increased understanding of the mediators and mechanisms of these processes is necessary if we are to develop strategies to protect individuals at risk and reduce the effect of air pollution on cardiovascular disease.
Within the SCOT-HEART (Scottish COmputed Tomography of the HEART Trial) trial of patients with stable chest pain, the use of coronary computed tomography angiography (CTA) reduced the rate of death ...from coronary heart disease or nonfatal myocardial infarction (primary endpoint).
This study sought to assess the consistency and mechanisms of the 5-year reduction in this endpoint.
In this open-label trial, 4,146 participants were randomized to standard care alone or standard care plus coronary CTA. This study explored the primary endpoint by symptoms, diagnosis, coronary revascularizations, and preventative therapies.
Event reductions were consistent across symptom and risk categories (p = NS for interactions). In patients who were not diagnosed with angina due to coronary heart disease, coronary CTA was associated with a lower primary endpoint incidence rate (0.23; 95% confidence interval CI: 0.13 to 0.35 vs. 0.59; 95% CI: 0.42 to 0.80 per 100 patient-years; p < 0.001). In those who had undergone coronary CTA, rates of coronary revascularization were higher in the first year (hazard ratio HR: 1.21; 95% CI: 1.01 to 1.46; p = 0.042) but lower beyond 1 year (HR: 0.59; 95% CI: 0.38 to 0.90; p = 0.015). Patients assigned to coronary CTA had higher rates of preventative therapies throughout follow-up (p < 0.001 for all), with rates highest in those with CT-defined coronary artery disease. Modeling studies demonstrated the plausibility of the observed effect size.
The beneficial effect of coronary CTA on outcomes is consistent across subgroups with plausible underlying mechanisms. Coronary CTA improves coronary heart disease outcomes by enabling better targeting of preventative treatments to those with coronary artery disease. (Scottish COmputed Tomography of the HEART Trial SCOT-HEART; NCT01149590)
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
After exposure to dilute diesel exhaust, men with coronary disease had increased exercise-induced myocardial ischemia, along with depressed fibrinolytic function. The data reported suggest possible ...mechanisms for the detrimental effect of air pollution from traffic in patients with coronary disease.
After exposure to dilute diesel exhaust, men with coronary disease had increased exercise-induced myocardial ischemia, along with depressed fibrinolytic function.
The World Health Organization (WHO) estimates that air pollution is responsible for 800,000 premature deaths worldwide each year.
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Short-term exposure to air pollution has been associated with increases in cardiovascular morbidity and mortality, with deaths due to ischemia, arrhythmia, and heart failure.
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In a large cohort study from the United States, Miller et al. recently reported that long-term exposure to air pollution increases the risk of death from cardiovascular disease by 76%.
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These associations are strongest for fine particulate air pollutants (particulate matter of less than 2.5 μm in aerodynamic diameter PM
2.5
), of which the combustion-derived nanoparticulate in . . .
High-sensitivity cardiac troponin I (cTnI) assays hold promise in detecting the transition from hypertrophy to heart failure in aortic stenosis. We sought to investigate the mechanism for troponin ...release in patients with aortic stenosis and whether plasma cTnI concentrations are associated with long-term outcome.
Plasma cTnI concentrations were measured in two patient cohorts using a high-sensitivity assay. First, in the Mechanism Cohort, 122 patients with aortic stenosis (median age 71, 67% male, aortic valve area 1.0 ± 0.4 cm(2)) underwent cardiovascular magnetic resonance and echocardiography to assess left ventricular (LV) myocardial mass, function, and fibrosis. The indexed LV mass and measures of replacement fibrosis (late gadolinium enhancement) were associated with cTnI concentrations independent of age, sex, coronary artery disease, aortic stenosis severity, and diastolic function. In the separate Outcome Cohort, 131 patients originally recruited into the Scottish Aortic Stenosis and Lipid Lowering Trial, Impact of REgression (SALTIRE) study, had long-term follow-up for the occurrence of aortic valve replacement (AVR) and cardiovascular deaths. Over a median follow-up of 10.6 years (1178 patient-years), 24 patients died from a cardiovascular cause and 60 patients had an AVR. Plasma cTnI concentrations were associated with AVR or cardiovascular death HR 1.77 (95% CI, 1.22 to 2.55) independent of age, sex, systolic ejection fraction, and aortic stenosis severity.
In patients with aortic stenosis, plasma cTnI concentration is associated with advanced hypertrophy and replacement myocardial fibrosis as well as AVR or cardiovascular death.
Air pollution exposure increases cardiovascular morbidity and mortality and is a major global public health concern.
We investigated the benefits of reducing personal exposure to urban air pollution ...in patients with coronary heart disease.
In an open randomized crossover trial, 98 patients with coronary heart disease walked on a predefined route in central Beijing, China, under different conditions: once while using a highly efficient face mask, and once while not using the mask. Symptoms, exercise, personal air pollution exposure, blood pressure, heart rate, and 12-lead electrocardiography were monitored throughout the 24-hr study period.
Ambient air pollutants were dominated by fine and ultrafine particulate matter (PM) that was present at high levels 74 μg/m³ for PM(2.5) (PM with aerodynamic diamater <2.5 µm). Consistent with traffic-derived sources, this PM contained organic carbon and polycyclic aromatic hydrocarbons and was highly oxidizing, generating large amounts of free radicals. The face mask was well tolerated, and its use was associated with decreased self-reported symptoms and reduced maximal ST segment depression (-142 vs. -156 μV, p = 0.046) over the 24-hr period. When the face mask was used during the prescribed walk, mean arterial pressure was lower (93 ± 10 vs. 96 ± 10 mmHg, p = 0.025) and heart rate variability increased (high-frequency power: 54 vs. 40 msec², p = 0.005; high-frequency normalized power: 23.5 vs. 20.5 msec, p = 0.001; root mean square successive differences: 16.7 vs. 14.8 msec, p = 0.007). However, mask use did not appear to influence heart rate or energy expenditure.
Reducing personal exposure to air pollution using a highly efficient face mask appeared to reduce symptoms and improve a range of cardiovascular health measures in patients with coronary heart disease. Such interventions to reduce personal exposure to PM air pollution have the potential to reduce the incidence of cardiovascular events in this highly susceptible population.
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BFBNIB, DOBA, IZUM, KILJ, NMLJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Calcific aortic stenosis, a relatively common problem in the elderly, has been found to be associated with atherosclerosis and hypercholesterolemia. This study found that, contrary to expectations, ...intensive lipid-lowering therapy with atorvastatin, which reduced low-density lipoprotein cholesterol levels to a mean of 63±23 mg per deciliter, had no effect on the progression of aortic stenosis (as measured by the aortic-jet velocity) or on aortic-valve calcification (as measured by helical computed tomographic scanning).
Intensive lipid-lowering therapy with atorvastatin had no effect on the progression of aortic stenosis or on aortic-valve calcification.
In the Western world, calcific aortic stenosis is the most common form of valvular heart disease, and its incidence increases with age such that 3 percent of adults over 75 years of age have aortic stenosis.
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It is a gradually progressive disease, characterized by a long asymptomatic phase, lasting several decades, followed by a shorter symptomatic phase associated with severe narrowing of the orifice of the aortic valve. Once symptoms occur, the prognosis is poor and surgery is usually mandated. Calcific aortic stenosis is now the leading indication for valve replacement in North America and Europe. However, there are currently . . .
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