Time- vs Step-Based Physical Activity Metrics for Health.

Importance: Current US physical activity (PA) guidelines prescribe moderate to vigorous PA (MVPA) time of at least 150 minutes per week for health. An analogous step-based recommendation has not been issued due to insufficient evidence. Objective: To examine the associations of MVPA time and step counts with all-cause mortality and cardiovascular disease (CVD). Design, Setting, and Participants: This cohort study analyzed data from an ongoing follow-up study of surviving participants of the Women's Health Study, a randomized clinical trial conducted from 1992 to 2004 in the US to evaluate use of low-dose aspirin and vitamin E for preventing cancer and CVD. Participants were 62 years or older who were free from CVD and cancer, completed annual questionnaires, and agreed to measure their PA with an accelerometer as part of a 2011-2015 ancillary study. Participants were followed up through December 31, 2022. Exposures: Time spent in MVPA and step counts, measured with an accelerometer for 7 consecutive days. Main Outcomes and Measures: The associations of MVPA time and step counts with all-cause mortality and CVD (composite of myocardial infarction, stroke, and CVD mortality) adjusted for confounders. Cox proportional hazards regression models, restricted mean survival time differences, and area under the receiver operating characteristic curve (AUC) were used to evaluate the associations. Results: A total of 14 399 women (mean [SD] age, 71.8 [5.6] years) were included. The median (IQR) MVPA time and step counts were 62 (20-149) minutes per week and 5183 (3691-7001) steps per day, respectively. During a median (IQR) follow-up of 9.0 (8.0-9.9) years, the hazard ratios (HR) per SD for all-cause mortality were 0.82 (95% CI, 0.75-0.90) for MVPA time and 0.74 (95% CI, 0.69-0.80) for step counts. Greater MVPA time and step counts (top 3 quartiles vs bottom quartile) were associated with a longer period free from death: 2.22 (95% CI, 1.58-2.85) months and 2.36 (95% CI, 1.73-2.99) months at 9 years follow-up, respectively. The AUCs for all-cause mortality from MVPA time and step counts were similar: 0.55 (95% CI, 0.52-0.57) for both metrics. Similar associations of these 2 metrics with CVD were observed. Conclusion and Relevance: Results of this study suggest that among females 62 years or older, MVPA time and step counts were qualitatively similar in their associations with all-cause mortality and CVD. Step count-based goals should be considered for future guidelines along with time-based goals, allowing for the accommodation of personal preferences.

The effect of diabetes on surgical versus percutaneous left main revascularization outcomes: a systematic review and meta-analysis.

BACKGROUND: The optimal method of coronary revascularization for diabetes mellitus (DM) patients with left main coronary artery disease (LMCAD) is controversial in the drug-eluting stent (DES) era. METHODS: We performed a systematic review and meta-analysis comparing DES-based percutaneous coronary intervention (PCI) to coronary artery bypass grafting (CABG) for LMCAD in DM patients and tested for effect measure modification (EMM) by diabetes for adverse events. We included all randomized controlled trials (RCTs) and observational studies comparing CABG to DES-based PCI including DM patients with LMCAD published up to March 1, 2021. We completed separate random-effects meta-analyses for four RCTs (4356 patients, mean follow-up of 4.9 years) and six observational studies (9360 patients, mean follow-up of 5.2 years). RESULTS: In RCTs among DM patients, DES-based PCI, compared to CABG, was associated with a 30% increased relative risk (RR) (RR 1.30, 95% CI 1.09-1.56, I2 = 0%), while among non-DM patients, there was a 25% increased relative risk (RR 1.25, 95% CI 1.07-1.44, I2 = 0%) for the composite endpoint of all-cause mortality, myocardial infarction, stroke, and unplanned revascularization (MACCE). There was no evidence of EMM (p-value for interaction = 0.70). The mean weighted SYNTAX score was 25.7. In observational studies, there was no difference between DES-based PCI and CABG for all-cause mortality in patients with DM (RR 1.13, 95% CI 0.91-1.40, I2 = 0%). CONCLUSIONS: CABG was superior to PCI for LMCAD in RCTs in DM patients for MACCE. Heart teams may consider DM as one of the many components in the clinical decision-making process, but may not want to consider DM as a primary deciding factor between DES-based PCI and CABG for LMCAD with low to intermediate anatomical complexity in the other coronary arteries. STUDY REGISTRATION: CRD42021246931 (PROSPERO).

Association of Modifiable Lifestyle Factors with Plasma Branched-Chain Amino Acid Metabolites in Women.

BACKGROUND: Circulating branched-chain amino acids (BCAAs-isoleucine, leucine, and valine) are strongly associated with higher risk of incident type 2 diabetes (T2D); however, determinants of elevated fasting BCAA concentrations are largely unknown. OBJECTIVES: We aimed to characterize the modifiable lifestyle factors related to plasma BCAAs. METHODS: We performed a cross-sectional analysis among n = 18,897 women (mean ± SD age: 54.9 ± 7.2 y) in the Women's Health Study, free of T2D and cardiovascular disease at baseline blood draw. Lifestyle factors, weight, and height were self-reported via questionnaire, including smoking status, alcohol, leisure-time physical activity (LTPA), diet quality scores [2010 Alternative Healthy Eating Index (without alcohol) (aHEI); alternate Mediterranean Diet (aMED)], and dietary sources of BCAAs. Plasma BCAAs were quantified via NMR spectroscopy. We calculated multivariable-adjusted percentage mean differences (95% CIs) and P values for linear trend of BCAAs stratified by categoric lifestyle factors. We estimated R2 from univariate cubic spline regression models to estimate the variability in BCAAs explained. RESULTS: Compared with women with BMI (in kg/m2) <25.0, BCAAs were 8.6% (95% CI: 8.0%, 9.3%), 15.3% (95% CI: 14.4%, 16.3%), and 21.0% (95% CI: 18.2%, 23.9%) higher for the BMI strata 25.0-29.9, 30.0-39.9, and ≥40.0, respectively (P-trend < 0.0001). Women with higher LTPA and higher alcohol intake compared with lower had modestly (∼1%) lower plasma BCAAs (P-trend = 0.014 and 0.0003, respectively). Differences in smoking status, aHEI, and aMED score were not related to plasma BCAAs. Women with higher dietary BCAAs had dose-response higher plasma BCAA concentrations, 3.4% (95% CI: 2.5%, 4.4%) higher when comparing the highest with the lowest quintile (P-trend < 0.0001). BMI explained 11.6% of the variability of BCAAs, whereas other factors explained between 0.1% and 1%. CONCLUSIONS: Our findings among a large cohort of US women indicate that BMI, but less so diet, physical activity, and other lifestyle factors, is related to plasma BCAAs.This trial was registered at clinicaltrials.gov as NCT00000479.

Prognostic Value of Coronary Sinus Flow Quantification by Cardiac Magnetic Resonance Imaging in Patients With Acute Myocardial Infarction.

Background This study aimed to evaluate the prognostic value of hyperemic coronary sinus flow (h-CSF) and global coronary flow reserve (g-CFR) obtained by phase-contrast cine-magnetic resonance imaging in patients with acute myocardial infarction (MI). Methods and Results This retrospective study analyzed patients with acute MI (n=523) who underwent primary (ST-segment-elevation MI) or urgent (non-ST-segment-elevation MI) percutaneous coronary intervention. Absolute coronary sinus blood flow (CSF) at rest and during vasodilator stress hyperemia was quantified at 30 days (24-36 days) after the index infarct-related lesion percutaneous coronary intervention and revascularization of functionally significant non-infarct-related lesions. We used Cox proportional hazards regression modeling to examine the association between h-CSF, g-CFR, and major adverse cardiac events defined as all-cause death, nonfatal MI, hospitalization for congestive heart failure, and stroke. Finally, 325 patients with ST-segment-elevation MI (62.1%) and 198 patients with non-ST-segment-elevation MI (37.9%) were studied over a median follow-up of 2.5 years. The rest CSF, h-CSF, and g-CFR were 0.94 (0.68-1.26) mL/min per g, 2.05 (1.42-2.73) mL/min per g, and 2.17 (1.54-3.03), respectively. Major adverse cardiac events occurred in 62 patients, and Cox proportional hazards analysis showed that h-CSF and g-CFR were independent predictors of major adverse cardiac events (h-CSF: hazard ratio [HR], 0.64; 95% CI, 0.47-0.88; P=0.005; g-CFR: HR, 0.62; 95% CI, 0.47-0.82; P=0.001). When stratified by h-CSF and g-CFR, cardiac event-free survival was the worst in patients with concordantly impaired h-CSF (<1.6 mL/min per g) and g-CFR (<1.7) (P<0.001). Conclusions Global coronary sinus flow quantification using phase-contrast cine-magnetic resonance imaging provided significant prognostic information independent of infarction size and conventional risk factors in patients with acute MI undergoing revascularization.

Association of Plasma Branched-Chain Amino Acid With Biomarkers of Inflammation and Lipid Metabolism in Women.

BACKGROUND: Branched-chain amino acids (BCAAs; isoleucine, leucine, and valine) correlate with insulin resistance and poor glucose control, which may in part explain associations between type 2 diabetes and cardiovascular disease. However, the relationships of BCAAs with other cardiometabolic pathways, including inflammation and dyslipidemia, are unclear. We hypothesized that plasma BCAAs would correlate with multiple pathways of cardiometabolic dysfunction. METHODS: We conducted a cross-sectional analysis among 19 472 participants (mean age=54.9 years, SD=7.2 years) in the Women's Health Study without a history of type 2 diabetes, cardiovascular disease, or cancer. We quantified the concentrations of individual biomarkers of inflammation and lipids, across quartiles of BCAAs, adjusting for age, smoking, body mass index, physical activity, and other established cardiovascular disease risk factors at blood draw. RESULTS: Women in the highest versus lowest quartiles of plasma BCAAs had higher inflammatory markers including high-sensitivity C-reactive protein (multivariable-adjusted means: 1.96 versus 1.43 mg/L), fibrinogen (367 versus 362 mg/dL), soluble intercellular cell adhesion molecule-1 (361 versus 353 ng/mL), and glycoprotein acetylation (407 versus 371 µmol/L; P trend=0.0002 for fibrinogen; P<0.0001 for others). Similarly for lipids, women with higher BCAAs had lower HDL-C (high-density lipoprotein cholesterol; 49.0 versus 55.0 mg/dL), and higher triglycerides (143 versus 114 mg/dL), LDL-C (low-density lipoprotein cholesterol; 133 versus 124 mg/dL), and lipoprotein insulin resistance score (52.6 versus 37.3; all: P<0.0001). Similar associations with these biomarkers were observed in isoleucine, leucine, and valine, respectively. CONCLUSIONS: Higher circulating BCAA concentrations are associated with adverse profiles of biomarkers of inflammation and dyslipidemia independent of established cardiovascular disease risk factors, and thus, may reflect poorer cardiometabolic health through multiple pathways. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00000479.

Prognostic Impact of Residual Anatomic Disease Burden After Functionally Complete Revascularization.

BACKGROUND: Prognostic impact of residual anatomic disease burden after functionally complete percutaneous coronary intervention (PCI), defined by post-PCI fractional flow reserve (FFR) >0.80 would be a clinically relevant question. The current study evaluated clinical outcomes at 2 years according to residual Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery (SYNTAX) score (RSS) in patients who underwent functionally complete revascularization. METHODS: A total of 1910 patients (2095 revascularized vessels) with post-PCI FFR >0.80 were selected from the International Post-PCI FFR Registry. RSS was defined as the SYNTAX score recalculated after PCI, SYNTAX revascularization index was calculated as 100×(1-RSS/pre-PCI SYNTAX score), and post-PCI FFR was measured after completion of PCI. The primary outcome was target vessel failure (TVF; a composite of cardiac death, target vessel-related myocardial infarction, and clinically driven target vessel revascularization) at 2 years, and risk of TVF was compared according to tertile classification of RSS (0, 1-5, and >5) and post-PCI FFR (≥0.94, 0.87-0.93, and ≤0.86). RESULTS: After PCI, SYNTAX score was changed from 10.0 (Q1-Q3, 7.0-16.0) to 0.0 (Q1-Q3, 0.0-5.0) and FFR changed from 0.70±0.12 to 0.90±0.05. TVF at 2 years occurred in 4.9%, and patients with TVF showed higher pre-PCI SYNTAX score and lower post-PCI FFR than those without. However, there were no significant differences in SYNTAX revascularization index and RSS. The risk of TVF was not different according to tertile of RSS (log-rank P=0.851). Conversely, risk of TVF was different according to tertile of post-PCI FFR (log-rank P=0.009). Multivariable model showed the risk of TVF was significantly associated with post-PCI FFR (hazard ratio, 1.091 [95% CI, 1.032-1.153]; P=0.002) but not with RSS (hazard ratio, 0.969 [95% CI, 0.898-1.045]; P=0.417). CONCLUSIONS: Among patients who underwent functionally complete revascularization, residual anatomic disease burden assessed by RSS was not related with occurrence of TVF at 2 years. These results support the importance of functionally complete revascularization rather than angiographic complete revascularization. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT04012281.

The association between simple renal cyst and aortic diseases: A systematic review and meta-analysis of observational studies.

OBJECTIVE: The objective of this meta-analysis of observational studies was to evaluate the association between simple renal cysts (SRC) and presence of aortic pathology such as aortic aneurysms and dissection. METHODS: We conducted searches in Ovid MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials from January 1960 to August 2019 to identify observational studies that examined the association between SRCs and any aortic diseases, including aortic aneurysms and dissection. Two reviewers independently extracted the data and assessed the risk of bias. The meta-analysis was performed by STATA 14.1. RESULTS: In total, 11 observational studies with 19 719 participants were included in this meta-analysis. Compared to individuals without SRCs, patients with SRCs had higher odds of abdominal aortic aneurysm (AAA) (adjusted OR = 2.61, 95% CI 2.34-2.91, P < 0.001, I2   = 0%), ascending thoracic aortic aneurysm (TAA) (adjusted OR = 1.98, 95% CI 1.09-3.63, P = 0.03, I2   = 90.1%), descending TAA (adjusted OR = 3.44, 95% CI, 2.67-4.43, P < 0.001, I2   = 0%), type A aortic dissection (AD) (adjusted OR = 1.98, 95% CI 1.32-2.96, P = 0.001, I2   = 12.9%), and type B AD (adjusted OR = 2.55, 95% CI, 1.31-4.96, P = 0.006, I2   = 76.2%). There was a higher average in the sum of diameter of SRCs among AAA compared to patients without AAA (WMD = 19.80 mm, 95% CI 13.92-25.67, P < 0.001, I2   = 63.8%). CONCLUSION: SRC is associated with higher odds of aortic diseases including AAA, ascending and descending TAA, type A and type B dissection even after adjusting for confounders.

Clinical significance of the presence of puff-chandelier ruptures detected by nonobstructive aortic angioscopy.

OBJECTIVE: This study aimed to investigate the prevalence and prognostic significance of atherosclerotic aortic plaques (AAPs) or specific AAP types detected by nonobstructive angioscopy (NOA) in patients who underwent percutaneous coronary intervention (PCI). BACKGROUND: Although recent studies have reported the presence of various patterns of AAPs, identified by NOA, the clinical significance of the presence of AAPs remains elusive. METHODS: In this retrospective, multicenter cohort study, a total of 167 patients who underwent PCI and intra-aortic scans with NOA were studied. The association between AAPs and the incidence of major adverse cardiac events (MACEs), including cardiac death, myocardial infarction, stroke, and clinically driven unplanned revascularizations, was assessed. RESULTS: AAPs were detected in 126 patients (75%) who underwent NOA. MACEs occurred in 28 (17%) patients during the follow-up (median 2.9 years [range 2.1-3.8]). Among all types of AAPs, only puff-chandelier rupture (PCR) showed a significant difference in frequency between patients with and those without MACEs: 21 (75%) and 49 (35%), respectively (p < .001). Multivariable Cox proportional hazard analysis revealed that PCR (hazard ratio [HR] 3.73, 95% confidence interval [CI] 1.57-8.87, p = .004) and chronic kidney disease (HR 2.97, 95% CI 1.37-6.44, p = .010) were independent predictors of MACEs. Kaplan-Meier analysis revealed that PCR was significantly associated with more frequent MACEs. CONCLUSION: The detection of PCR in the aorta using NOA was significantly associated with an increased risk of subsequent adverse events after PCI.

Circulatory dynamics changes are an additional predictor of successful pulmonary vein isolation during cryoballoon ablation.

The association between circulatory dynamics changes during cryoballoon applications and a successful pulmonary vein isolation (PVI) is unknown. Seventy atrial fibrillation patients who underwent PVI with 28-mm second-generation cryoballoons and single 3-min freezes were included. Intra-procedural parameters including circulatory dynamics changes during cryoapplications, were compared between 113 successful applications (30 left superior PVs[LSPVs], 30 left inferior PVs[LIPVs], 25 right superior PVs[RSPVs], and 28 right inferior PVs[RIPVs]) and 47 failed applications (10 LSPVs, 9 LIPVs, 8 RSPVs, and 20 RIPVs). In all individual PVs, lower nadir balloon temperatures (MinTemps) and longer thawing times (ThawTimes) significantly predicted a successful PVI. In addition, greater systolic blood pressure drops following releasing the PV occlusion (SBP-drops) significantly predicted a successful right PV PVI, and longer elapse times during SBP-drops significantly predicted a successful RIPV PVI. Composite parameters incorporating MinTemps and ThawTimes, SBP-drops, and ThawTimes showed the highest area under the curve to predict a successful left PV (0.876 for LSPVs, 0.851 for LIPVs) and right PV (0.927 for RSPVs, 0.980 for RIPVs) PVI, respectively. If the ThawTime (≥ 30 s) and SBP-drop (≤ - 21 mmHg) cutoff values were achieved for the RIPVs, the positive predictive value was 100%. In contrast, if both criteria were not achieved for the RIPVs, the negative predictive value was 100%. In the second-generation cryoballoon PVI, the MinTemp and ThawTime were significantly associated with acute success for all four PVs. In addition, SBP-drops further improved the accuracy of predicting a successful right PV PVI, especially of the RIPV.

Validation of electrical ostial pulmonary vein isolation verified with a spiral inner lumen mapping catheter during second-generation cryoballoon ablation.

BACKGROUND: Achieve catheters are cryoballoon guidewires that enable pulmonary vein (PV) potential mapping. The single catheter approach in conjunction with the Achieve catheter is currently standard practice in second-generation cryoballoon ablation, yet circumferential mapping catheters are the gold standard for evaluating PV isolation (PVI). The study sought to validate the ostial PVI verified by an Achieve catheter alone. METHODS: One hundred fifty-one paroxysmal atrial fibrillation patients undergoing PVI using exclusively 28-mm second-generation cryoballoons were enrolled. PV recordings were analyzed during (real-time recordings) and after cryoballoon applications with 20-mm Achieve mapping catheters, and subsequently validated by 20-mm conventional circumferential mapping catheters. RESULTS: Out of 596 PVs, 576 (96.6%) were isolated using cryoballoons, and 20 required touch-up ablation. PVI was verified during cryoballoon applications with real-time monitoring in 299, and after applications in 280 PVs by Achieve catheters alone. The time-to-isolation was 27.2 ± 22.0 seconds. Validation with standard circumferential mapping catheters confirmed ostial PVIs in 296 of 299 (99.0%) PVs that real-time PVI was obtained during applications, and in 242 of 280 (86.5%) PVs that PV activities were not visible during applications and PVI was verified after the applications. The accuracy of ostial PVIs with Achieve catheters in PVs without obtaining real-time PV recordings was 40/47 (85.1%), 58/65 (89.2%), 77/79 (97.5%), 61/81 (75.3%), and 6/8 (75.0%) in left superior, left inferior, right superior, right inferior, and left common PVs, respectively. CONCLUSIONS: In second-generation 28-mm cryoballoon ablation, verification of ostial PVIs using Achieve mapping catheters alone might not be sufficient to accurately confirm an ostial PVI when real-time PVI was not obtained.

A selective peroxisome proliferator-activated receptor-ß/δ agonist attenuates neointimal hyperplasia after wire-mediated arterial injury.

BACKGROUND: Neointimal hyperplasia after the percutaneous coronary intervention is still a clinically serious problem, associated with the risk of thrombosis due to delayed reendothelization. Peroxisome proliferator-activated receptor-ß/δ (PPAR-ß/δ) belongs to a family of ligand-activated transcription factors. OBJECTIVES: In this study, we investigated the effects of GW-0742, a synthetic high-affinity PPAR-ß/δ agonist, on neointimal hyperplasia after arterial injury. Using C57BL/6J mice, we made a wire-injury model and intraperitoneally injected GW-0742 or vehicle once a day. The arteries were harvested for pathological and molecular analysis on day 14 after injury. In vitro, vascular smooth muscle cells (VSMCs), macrophages and human umbilical vein endothelial cells (HUVECs) were cultured, and GW-0742 effects on the cells proliferation were measured. RESULTS: The vehicle-treated injured arteries showed significantly thickened intima, while GW-0742 suppressed it. GW-0742 significantly suppressed IL-6 protein production, the expression of proliferating cell nuclear antigen in the neointima and enhanced CD31 expression. In vitro, GW-0742 attenuated VSMC proliferation triggered by cytokines or macrophages. The drug also induced endothelial regeneration after denudation injury. CONCLUSION: The data suggest that the PPAR-ß/δ agonist is effective for atten- uation of neointimal hyperplasia by suppressing VSMC proliferation and accelerating reendothelization.