Circulation: Clinical Summaries
Original Research Put Into Perspective for the Practicing Clinician
- A Nutrient-Wide Association Study on Blood Pressure
- The Safety of Cardiopulmonary Exercise Testing in a Population With High-Risk Cardiovascular Diseases
- Anti-Tumor Necrosis Factor-α Therapy Reduces Aortic Inflammation and Stiffness in Patients With Rheumatoid Arthritis
- Age, Sex, and Hypertension-Related Remodeling Influences Left Ventricular Torsion Assessed by Tagged Cardiac Magnetic Resonance in Asymptomatic Individuals: The Multi-Ethnic Study of Atherosclerosis
- The Angiogenic Factor Secretoneurin Induces Coronary Angiogenesis in a Model of Myocardial Infarction by Stimulation of Vascular Endothelial Growth Factor Signaling in Endothelial Cells
- Coronary Artery Bypass Surgery With or Without Mitral Valve Annuloplasty in Moderate Functional Ischemic Mitral Regurgitation: Final Results of the Randomized Ischemic Mitral Evaluation (RIME) Trial
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A Nutrient-Wide Association Study on Blood Pressure
Raised blood pressure (BP) is a major risk factor for coronary heart disease and stroke. Risk increases in graded fashion across the BP range, with substantial risk of death and disability attributed to raised BP at normal and high-normal BPs, below current treatment thresholds. Thus, nonpharmacologic as well as pharmacological approaches are needed to deal with the population-wide BP problem. Dietary habits are known to be related to high BP, but the role of many nutrients is unclear despite intensive research efforts. We used a nutrient-wide association study design to systematically test and validate multiple associations between a wide range of nutrients and BP. We initially tested associations of 82 nutrients and 3 urine electrolytes/electrolyte ratios with BP in a 50% random sample of the population-based study, the International Collaborative Study on Macro-/Micronutrients and Blood Pressure (INTERMAP). Significant findings were validated in the remainder 50% INTERMAP population and among participants in the National Health and Nutrition Examination Survey (NHANES). We identified inverse associations between BP and intake of B vitamins (folacin, riboflavin, thiamin) previously poorly studied, and reidentified sodium-to-potassium ratio and alcohol with BP (direct), and non-heme iron, phosphorus, and magnesium intake with systolic BP (inverse). Our results highlight a complex array of nutritional correlates with BP and emphasize why traditional approaches of testing 1 association at a time may be suboptimal compared with our inclusive nutrient-wide association study paradigm. Findings for BP and B vitamins may represent potentially causative associations, which need to be probed in further observational and interventional studies. See p 2456.
The Safety of Cardiopulmonary Exercise Testing in a Population With High-Risk Cardiovascular Diseases
Cardiopulmonary exercise testing (CPX) with measurement of peak oxygen uptake (Vo2) is the most accurate test for quantification of functional impairment resulting from cardiovascular disease. CPX has primarily been applied in patients with congestive heart failure to help select candidates for heart transplantation. There are other cardiovascular disorders (aortic stenosis, hypertrophic cardiomyopathy, pulmonary hypertension, and congenital heart disease) for which accurate assessment of functional capacity could serve as a useful aid in the clinical management of these patients. However, CPX has not been widely applied in these patient subsets, in part because of limited availability of safety data. This study investigated safety of CPX in 4250 patients with a wide variety of underlying high-risk cardiovascular diseases who underwent a total of 5060 tests. CPX was found to be reasonably safe in this study cohort, with an adverse event rate of 0.16% and no fatal events. This research may lead to further clinical application of CPX in these patient subsets. See p 2465.
Anti-Tumor Necrosis Factor-α Therapy Reduces Aortic Inflammation and Stiffness in Patients With Rheumatoid Arthritis
Rheumatoid arthritis is a systemic inflammatory condition associated with increased cardiovascular risk. This is not fully explained by traditional risk factors, but direct vascular inflammation and aortic stiffening may play a role. In this study, we have demonstrated that patients with rheumatoid arthritis have increased inflammation along the entire length of the aorta in comparison with age-matched patients who have cardiovascular disease and that anti-tumor necrosis factor-α therapy leads to a reduction of inflammation in the whole aorta and in the most diseased segment, as well, and to a decrease in aortic stiffness. Our data suggest that vascular inflammation could underpin the mechanism of increased cardiovascular disease seen in rheumatoid arthritis and propose that effective control of inflammation may reduce cardiovascular disease risk in patients with rheumatoid arthritis. Furthermore, our study demonstrates that positron emission tomography/computed tomography scanning could be a useful tool for cardiovascular disease risk stratification and for monitoring risk reduction of anti-inflammatory therapies in patients with chronic inflammatory diseases. See p 2473.
Age, Sex, and Hypertension-Related Remodeling Influences Left Ventricular Torsion Assessed by Tagged Cardiac Magnetic Resonance in Asymptomatic Individuals: The Multi-Ethnic Study of Atherosclerosis
Left ventricular (LV) systolic torsion limits myocardial energy consumption and minimizes transmural fiber stress gradients and oxygen demand, resulting in a more efficient contraction in the mathematical model. According to the lever-arm theory, a greater radius difference between the endocardium and the epicardium such as concentric hypertrophy would result in increased torsion. In addition, reduced subendocardial function would result in less opposition to the dominant epicardium and finally enhanced torsion because helical contraction of subendocardial and subepicardial muscle layers would counteract one another. However, the influence of LV remodeling associated with age, sex, and hypertension on LV torsion is not well understood. Therefore, we used cardiac magnetic resonance imaging to examine LV structure and function among 1478 participants of the Multi-Ethnic Study of Atherosclerosis who had no cardiovascular disease at baseline. In multivariable regression models, older age was associated with lower LV volumes, higher relative wall thickness, and a significant fall in stoke volume, along with lower myocardial shortening. However, torsion was greater with old age (0.14°/cm per decade; P<0.001). The smaller LV and higher contraction of women's hearts were accompanied by the greater torsion (0.37°/cm versus men; P<0.001). Finally, although hypertension is associated with concentric hypertrophy and lower circumferential shortening, torsion is greater in hypertensive individuals independently of age and sex (0.17°/cm versus nonhypertension; P<0.05). These findings suggest that torsion represents a compensatory mechanism that maintains an adequate stroke volume and cardiac output in the face of progressively reduced LV volumes and myocardial shortening associated with ageing and/or hypertension. See p 2481.
The Angiogenic Factor Secretoneurin Induces Coronary Angiogenesis in a Model of Myocardial Infarction by Stimulation of Vascular Endothelial Growth Factor Signaling in Endothelial Cells
Our work shows that the angiogenic factor secretoneurin improves left ventricular function in an animal model of myocardial infarction. Secretoneurin stimulates angiogenesis and arteriogenesis in the infarct border zone and reduces scar size after the infarct. Mechanistically, secretoneurin exerts beneficial effects on coronary endothelial cells via stimulation of growth factor receptors for angiogenic cytokines such as vascular endothelial growth factor or fibroblast growth factor. Secretoneurin thereby stimulates binding of vascular endothelial growth factor to its coreceptors neuropilin-1 and heparan sulfate proteoglycans. Despite promising preclinical and early clinical data for the application of angiogenic cytokines in the treatment of ischemic heart or limb disease (a therapeutic strategy termed therapeutic angiogenesis), randomized phase III clinical trials (Angiogenic GENe Therapy [AGENT] trial for coronary heart disease, Therapeutic Angiogenesis for Management of Arteriopathy in a Randomized International Study [TAMARIS] for critical limb ischemia) did not show the expected results. In addition to patient and study end point selection and pharmacokinetic issues, it is also conceivable that administration of a single angiogenic factor is not sufficient to orchestrate a complex biological event like the growth of a new blood vessel. Indeed, a combination of angiogenic growth factors (such as basic fibroblast growth factor and platelet-derived growth factor or basic fibroblast growth factor and hepatocyte growth factor) exerted more potent and long-lasting angiogenic responses and beneficial effects in ischemic diseases compared with administration of single factors. In this context, it is of particular interest that secretoneurin, as a single compound, stimulated receptors for several of these cytokines like vascular endothelial growth factor or fibroblast growth factor. We therefore think that secretoneurin may be a promising candidate for therapeutic angiogenesis. See p 2491.
Coronary Artery Bypass Surgery With or Without Mitral Valve Annuloplasty in Moderate Functional Ischemic Mitral Regurgitation: Final Results of the Randomized Ischemic Mitral Evaluation (RIME) Trial
The role of mitral valve repair (MVR) during coronary artery bypass grafting (CABG) in patients with moderate ischemic mitral regurgitation is uncertain. We randomized 73 patients referred for CABG with moderate ischemic mitral regurgitation and an ejection fraction >30% to receive either CABG plus MVR (34 patients) or CABG only (39 patients). At 1 year, patients in the CABG plus MVR group had a significantly greater improvement in functional capacity as measured by peak oxygen consumption, and greater left ventricular reverse remodeling as measured by the left ventricular end-systolic volume index, reduction in mitral regurgitation severity, and B-type natriuretic peptide levels, compared with the CABG-only group. However, operation duration, blood transfusion, intubation duration, and hospital stay duration were greater in the CABG plus MVR group. There was also a trend towards higher complication rates in the CABG plus MVR group, although this was not statistically significant. Deaths at 30 days and 1 year were similar in both groups, as was the incidence of hospitalization for heart failure. The results of this study support the addition of MVR to CABG in patients with moderate ischemic mitral regurgitation undergoing CABG, but the benefits of the combined procedure must be balanced against a possible increased risk of morbidity in the perioperative period. The impact of the benefits reported in this study on longer term clinical outcomes remains to be defined. See p 2502.
- © 2012 American Heart Association, Inc.
- A Nutrient-Wide Association Study on Blood Pressure
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