Lifelong restriction of dietary branched-chain amino acids has sex-specific benefits for frailty and lifespan in mice.

Protein restricted (PR) diets promote health and longevity in many species. While the precise components of a PR diet that mediate the beneficial effects to longevity have not been defined, we recently showed that many metabolic effects of PR can be attributed to reduced dietary levels of the branched-chain amino acids (BCAAs) leucine, isoleucine, and valine. Here, we demonstrate that restricting dietary BCAAs increases the survival of two different progeroid mouse models, delays frailty and promotes the metabolic health of wild-type C57BL/6J mice when started in midlife, and leads to a 30% increase in lifespan and a reduction in frailty in male, but not female, wild-type mice when fed lifelong. Our results demonstrate that restricting dietary BCAAs can increase healthspan and longevity in mice, and suggest that reducing dietary BCAAs may hold potential as a translatable intervention to promote healthy aging.

Diagnosis and surgical management of subaortic stenosis and mitral valve systolic anterior motion.

The case is reported of a patient with a previously undiagnosed cause of severe congestive heart failure (CHF) caused by the presence of a discrete subaortic stenosis (SAS) from a subvalvular membrane (SVM). The clinical decision making was complicated by the concurrent presence of systolic anterior motion (SAM) of the mitral valve leaflet. Due to the limitations and eventual failure of physiologically opposing medical management strategies, the patient eventually required an open-heart surgical approach and underwent intraoperative SVM resection. A persistent intraoperative left ventricular outflow tract (LVOT) gradient of 50 mmHg due to SAM prompted mitral valve replacement, which resulted in a complete resolution of the LVOT gradient and symptoms. In this extremely rare scenario of SAS and SAM, when SVM resection is thought to be inadequate to relieve LVOT obstruction due to the concurrent presence of SAM, mitral valve replacement represents a reasonable therapeutic approach.

Red cell distribution width as a bleeding predictor after percutaneous coronary intervention.

BACKGROUND: Red cell distribution width (RDW), a measure of variability in the size of circulating erythrocytes, is an independent predictor of mortality in cardiovascular disease and in patients undergoing percutaneous coronary intervention (PCI). We set out to determine if RDW is a prognostic marker of major bleeding post-PCI. METHODS: The study population included 6,689 patients who were subjected to PCI. The RDW was derived from a complete blood count drawn before PCI. Major inhospital bleeding was defined as a hematocrit decrease ≥12%, hemoglobin drop of ≥4, transfusion of ≥2 units of packed red blood cells, retroperitoneal, or gastrointestinal or intracranial bleeding. Multivariable logistic analysis of major inhospital bleeding was performed using a logistic regression model that comprised the National Cardiovascular Data Registry (NCDR) risk score model as a single variable. RESULTS: Major bleeding (P < .001), vascular complications (P = .005), and transfusions (P < .001) were significantly higher in patients with higher baseline RDW values. After adjustment for known bleeding correlates, RDW was a significant predictor for major bleeding (odds ratio 1.12, 95% CI 1.06-1.19, P < .001). Although the c statistic of the NCDR risk prediction model changed from 0.730 to 0.737 (P = .032), the net reclassification improvement increased significantly after the addition of RDW as a continuous variable (17.3% CI 6.7%-28%, P = .002). CONCLUSIONS: Red cell distribution width, an easily obtainable marker, has an independent, linear relationship with major bleeding post-PCI and incrementally improves the well-validated NCDR risk prediction model. These data suggest that further investigation is necessary to determine the relationship of RDW and post-PCI bleeding.

Discordant association of C-reactive protein with clinical events and coronary luminal narrowing in postmenopausal women: data from the Women's Angiographic Vitamin and Estrogen (WAVE) study.

BACKGROUND: The incidence of cardiovascular events had been shown to be associated with C-reactive protein (CRP). However, it is unclear that the cardiovascular risk associated with CRP is due to progressive coronary narrowing or to other factors such as formation of unstable plaque. This study was designed to determine the effect of baseline CRP on cardiovascular events and on the progression of atherosclerotic narrowing among 423 postmenopausal women with angiographic stenosis between 15% and 75%. HYPOTHESIS: Baseline CRP levels may affect cardiovascular events and progression of atherosclerotic coronary artery narrowing among postmenopausal women. METHODS: Baseline and follow-up (2.8 years) angiographic data were analyzed among 320 women. Women were stratified into 4 quartiles according to baseline CRP levels. The changes in lumen diameter and clinical events in each quartile were compared. RESULTS: The annualized changes in minimal and average lumen diameter in diseased and nondiseased coronary segments were not significantly associated with baseline CRP levels. The composite end point of all-cause mortality and myocardial infarction (MI) increased from 3% (3/107) in the first CRP quartile to 14% (14/98) in fourth CRP quartile (P < 0.001). Similar results were found for cardiovascular death and MI (increased from 1% (2/107) in the first quartile to 11% (11/98) in fourth quartile). The difference remained significant even after adjustment for baseline differences and cardiovascular risk factors. CONCLUSIONS: Higher baseline CRP was associated with increased risk of clinical events but was not associated with annualized change in luminal diameters. Thus, increased risk of adverse events among patients with higher baseline CRP events was independent of progression of atherosclerosis as measured by change in minimal or average luminal diameter.

Effect of cystatin C levels on angiographic atherosclerosis progression and events among postmenopausal women with angiographically decompensated coronary artery disease (from the Women's Angiographic Vitamin and Estrogen [WAVE] study).

End-stage renal disease and mild renal insufficiency are associated with increased cardiovascular risk. Cystatin C, a novel marker of kidney function, was found to be associated with a higher frequency of cardiovascular events and mortality independent of glomerular filtration rate. It remained uncertain, however, whether enhanced cardiovascular risk associated with cystatin C is due to accelerated progression of atherosclerosis or to plaque instability. The aim of this study was to examine the effects of baseline cystatin C on annual change in coronary artery narrowing and clinical events in 423 postmenopausal women with angiographically documented coronary artery disease enrolled in the Women's Angiographic Vitamin and Estrogen (WAVE) trial. Baseline and follow-up (mean 2.8 ± 0.9 years) angiography was performed in 320 women. Angiographic progression of disease and clinical events in each cystatin C quartile were compared. Women with cystatin C levels in the highest quartile were older and more likely to have histories of heart failure and stroke. Annualized changes in minimal and average luminal diameters were similar in diseased and nondiseased segments. All-cause death or myocardial infarction (3.6% vs 15.6%, p <0.001), cardiovascular death or myocardial infarction (2.3% vs 13.5%, p <0.001), and cardiovascular events (3.6% vs 13.5%, p <0.001) were significantly higher in women with baseline cystatin C levels in the highest quartile compared with women with cystatin C levels in the lower 3 quartiles. The risk for clinical events associated with cystatin C remained significantly higher in multivariate logistic regression analysis after adjusting for baseline differences and cardiovascular risk factors. The risk for clinical events was also independent of estimated glomerular filtration rate. In conclusion, in postmenopausal women with angiographically documented coronary artery disease, baseline cystatin C levels were associated with worse clinical outcomes without accelerated progression of atherosclerosis.

Complexity of the relation between hemoglobin A1C, diabetes mellitus, and progression of coronary narrowing in postmenopausal women.

The aim of this study was to assess the effect of diabetes mellitus (DM) and glycosylated hemoglobin (HbA1c) on the progression of atherosclerosis in postmenopausal women. A retrospective analysis of the Women's Angiographic and Vitamin and Estrogen (WAVE) trial, a multicenter randomized trial on progression of atherosclerosis in postmenopausal women, was performed. Baseline and follow-up angiography was performed in 320 women. Minimum luminal diameter and average luminal diameter at baseline and follow-up were measured in 1,735 coronary segments. Measurements and adverse events were grouped on the basis of history of DM and HbA1c. DM was associated with more total cardiac events but with similar rates of death or myocardial infarction. There were greater reductions in minimum luminal diameter and average luminal diameter in segments from patients with known DM (p <0.001) and with a baseline HbA1c ≥6.5% (p = 0.002 and p = 0.004, respectively). The greater reductions in minimum luminal diameter and average luminal diameter in the higher HbA1c strata were only in patients with known DM. More new lesions, however, appeared with baseline HbA1c ≥5.7%, irrespective of a history of DM. In conclusion, the relation between DM and the progression of coronary narrowing in postmenopausal women is complex. Clinically apparent DM, not elevated HbA1c alone, appears to promote the progression of established coronary lesions even in HbA1c ranges diagnostic of pre-DM and DM. This raises the possibility that coronary narrowing of existing stenosis in women with DM may be due to negative remodeling, a complex process that might be less dependent on hyperglycemia than new lesion formation.