Stem cell therapy is a potentially effective and promising treatment for ischemic heart disease. Resistin, a type of adipokine, has been found to bind to adipose-derived mesenchymal stem cells (ADSCs). However, the effects of resistin on cardiac homing by ADSCs and on ADSC-mediated cardioprotective effects have not been investigated. ADSCs were obtained from enhanced green fluorescent protein transgenic mice. C57BL/6J mice were subjected to myocardial ischemia-reperfusion (I/R) or sham operations. Six hours after the I/R operation, mice were intravenously injected with resistin-treated ADSCs (ADSC-resistin) or vehicle-treated ADSCs (ADSC-vehicle). Cardiac homing by ADSCs and cardiomyocyte apoptosis were investigated 3 days after I/R. Cardiac function, fibrosis, and angiogenesis were evaluated 4 wk after I/R. Cellular and molecular mechanisms were investigated in vitro using cultured ADSCs. Both immunostaining and flow cytometric experiments showed that resistin treatment promoted ADSC myocardial homing 3 days after intravenous injection. Echocardiographic experiments showed that ADSC-resistin, but not ADSC-vehicle, significantly improved left ventricular ejection fraction. ADSC-resistin transplantation significantly mitigated I/R-induced fibrosis and reduced atrial natriuretic peptide/brain natriuretic peptide mRNA expression. In addition, cardiomyocyte apoptosis was reduced, whereas angiogenesis was increased by ADSC-resistin treatment. At the cellular level, resistin promoted ADSC proliferation and migration but did not affect H2O2-induced apoptosis. Molecular experiments identified the ERK1/2-matrix metalloproteinase-9 pathway as a key component mediating the effects of resistin on ADSC proliferation and migration. These results demonstrate that resistin can promote homing of injected ADSCs into damaged heart tissue and stimulate functional recovery, an effect mediated through the ERK1/2 signaling pathway and matrix metalloproteinase-9. NEW & NOTEWORTHY First, intravenous injection of adipose-derived mesenchymal stem cells (ADSCs) treated with resistin significantly increased angiogenesis and reduced myocardial apoptosis and fibrosis in a murine model of ischemia-reperfusion, resulting in improved cardiac performance. Second, resistin treatment significantly increased myocardial homing of intravenously delivered ADSCs. Finally, the ERK1/2-matrix metalloproteinase 9 pathway contributed to the higher proliferative and migratory capacities of ADSCs treated with resistin.
The purpose of the Multivessel TALENT trial is to compare clinical outcomes of the novel Supraflex Cruz stent with those of the SYNERGY stent in patients with three-vessel disease (3VD) undergoing state-of-the-art percutaneous coronary intervention (PCI).In this prospective, randomised, 1:1 balanced, multicentre, open-label trial, 1,550 patients with de novo 3VD without left main disease will be assigned to the Supraflex Cruz or SYNERGY arm. The following treatment principles of "best practice" PCI will be applied: Heart Team consensus based on SYNTAX score II treatment recommendation, functional lesion evaluation by quantitative flow ratio (QFR), stent optimisation by intravascular imaging, optimal pharmacological treatment and prasugrel monotherapy. The primary endpoint is a non-inferiority comparison of the patient-oriented composite endpoint (POCE) of all-cause death, any stroke, any myocardial infarction, or any revascularisation, at 12 months post procedure. The powered secondary endpoint is a superiority comparison of the vessel-oriented composite endpoint (VOCE), defined as vessel-related cardiovascular death, vessel-related myocardial infarction, or clinically and physiologically indicated target vessel revascularisation, at 24 months.The Multivessel TALENT trial will be evaluating a novel treatment strategy for complex coronary artery disease with state-of-the-art PCI based on angiography-derived QFR with novel ultra-thin Supraflex Cruz stents, compared with SYNERGY stents. Clinical Trial Registration URL: https://www.clinicaltrials.gov/ct2/show/NCT04390672. Unique Identifier: NCT04390672
The receptor for advanced glycation end products (RAGE) and thioredoxin (Trx) play opposing roles in diabetic myocardial ischemia-reperfusion (MI/R) injury. We recently demonstrated nitrative modification of Trx leads to its inactivation and loss of cardioprotection. The present study is to determine the relationship between augmented RAGE expression and diminished Trx activity pertaining to exacerbated MI/R injury in the diabetic heart. The diabetic state was induced in mice by multiple intraperitoneal low-dose streptozotocin injections. RAGE small-interfering RNA (siRNA) or soluble RAGE (sRAGE, a RAGE decoy) was via intramyocardial and intraperitoneal injection before MI/R, respectively. Mice were subjected to 30 min of myocardial infarction followed by 3 or 24 h of reperfusion. At 10 min before reperfusion, diabetic mice were randomized to receive EUK134 (peroxynitrite scavenger), recombinant hTrx-1, nitrated Trx-1, apocynin (a NADPH oxidase inhibitor), or 1400W [an inducible nitric oxide synthase (iNOS) inhibitor] administration. The diabetic heart manifested increased RAGE expression and N ε -(carboxymethyl)lysine (CML, major advanced glycation end product subtype) content, reduced Trx-1 activity, and increased Trx nitration after MI/R. RAGE siRNA or administration of sRAGE in diabetic mice decreased MI/R-induced iNOS and gp91 phox expression, reduced Trx nitration, preserved Trx activity, and decreased infarct size. Apocynin or 1400W significantly decreased nitrotyrosine production and restored Trx activity. Conversely, administration of either EUK134 or reduced hTrx, but not nitrated hTrx, attenuated MI/R-induced superoxide production, RAGE expression, and CML content and decreased cardiomyocyte apoptosis in diabetic mice. Collectively, we demonstrate that RAGE modulates the MI/R injury in a Trx nitrative inactivation fashion. Conversely, nitrative modification of Trx blocked its inhibitory effect upon RAGE expression in the diabetic heart. This is the first direct evidence demonstrating the alternative cross talk between RAGE overexpression and nitrative Trx inactivation, suggesting that interventions interfering with their interaction may be novel means of mitigating diabetic MI/R injury.
AIM To study the biliary excretion of genistein and its metabolite at different doses in rats. METHODS Suspended in 0.5% CMC-Na solution, genistein was orally administered to rats at the dose of 6.25, 12.5 and 50 mg x kg(-1), separately. At various time intervals, the bile was collected. The bile was treated with beta-glucuronidase. The genistein in bile was extracted twice by vortexing with 2.0 mL mixture of methyl tert-tubtyl ether and pentane (8:2). The organic phase was removed into the tubes and then evaporated in ventilation cabinet. The residue was dissolved in 50 microL of methanol. Twenty microL solution was drawn and detected by high-performance liquid chromatography. RESULTS The accumulative biliary excretion of genistein was (42.56 +/- 6.54) , (75.17 +/- 18.87) and (126.60 +/- 34.78) microg at the dose of 6.25, 12.5 and 50 mg x kg(-1), respectively. The total drug (genistein plus glucuronidated genistein) excreted from bile was (108.46 +/- 35.23), (423.46 +/- 158.31) and ( 853.74 +/- 320. 84) microg, and the ratio of glucuronidated genistein was 60.76% , 82.25% and 85.17% at the dose of 6.25, 12.5 and 50 mg x kg(-1), respectively. CONCLUSION The genistein was excreted mainly in the form of glucuronidated genistein in rat bile. The genistein and glucuronidated genistein were excreted in a nonlinear dose-dependent manner.
Abstract Background The utility of the PRECISE-DAPT score in predicting short-term major bleeding, either alone, or in comparison with the CRUSADE and ACUITY scores, has not been investigated. This analysis compared the predictive performances of the three bleeding scores in stratifying the risk of 30-day major bleeding postpercutaneous coronary intervention in patients with dual-antiplatelet therapy. Methods In this post hoc subanalysis of the GLOBAL LEADERS trial, the primary safety objective (bleeding according to the Bleeding Academic Research Consortium [BARC] criteria [type 3 or 5]) was assessed at 30 days according to the three scores in the overall population, and in patients with acute (ACS) and chronic coronary syndrome (CCS). Results In a total of 15,968 patients, we calculated all three scores in 14,709 (92.1%). Irrespective of clinical presentation, the PRECISE-DAPT (c-statistics: 0.648, 0.653, and 0.641, respectively), CRUSADE (c-statistics: 0.641, 0.639, and 0.644, respectively), and ACUITY (c-statistics: 0.633, 0.638, and 0.623, respectively) scores were no significant between-score differences in discriminatory performance for BARC 3 or 5 bleeding up to 30 days, and similarly the PRECISE-DAPT score had a comparable discriminative capacity according to the integrated discrimination improvement when compared with the other scores. In ACS, the CRUSADE score had a poor calibration ability (Hosmer–Lemeshow goodness-of-fit [GOF] chi-square = 15.561, p = 0.049), whereas in CCS, the PRECISE-DAPT score had poor calibration (GOF chi-square = 15.758, p = 0.046). Conclusion The PRECISE-DAPT score might be clinically useful in the overall population and ACS patients for the prediction of short-term major bleeding considering its discriminative and calibration abilities.
Balloon rupture during transcatheter aortic valve replacement (TAVR) is a rare but serious complication. We present two cases of balloon rupture in patients with severe aortic stenosis and type 0 bicuspid aortic valve. Three-dimensional models based on pre-procedure cardiac CT angiography were used to post hoc investigate these cases. The models revealed asymmetrical distribution of calcifications with sharp spiked features in bicuspid aortic valves. The narrow and calcified orifice resulted in uneven force distribution on the expanded balloon, leading to balloon rupture. Furthermore, we reviewed the classification and causes of balloon rupture and summarized avoidance methods and treatment options. Accurate pre-procedural anatomy evaluation and computer modeling are crucial for planning and managing TAVR procedures. Further investigation through computer simulation is needed to determine the appropriate balloon size and inflation locations to provide the reference of preparation pre-procedure.
Numerous studies have demonstrated a paradoxical association between higher baseline body mass index (BMI) and lower long-term mortality risk after coronary revascularization, known as the “obesity paradox”, possibly relying on the single use of BMI. The current study is a post-hoc analysis of the SYNTAX Extended Survival (SYNTAXES) trial, which is the extended follow-up of the SYNTAX trial comparing percutaneous coronary intervention (PCI) versus coronary artery bypass graft (CABG) in patients with left-main coronary artery disease (LMCAD) or three-vessel disease (3VD). Patients were stratified according to baseline BMI and/or waist circumference (WC). Out of 1,800 patients, 1,799 (99.9%) and 1,587 (88.2%) had available baseline BMI and WC data, respectively. Of those, 1,327 (73.8%) patients had High BMI (≥25 kg/m2), whereas 705 (44.4%) patients had High WC (>102 cm for men or >88 cm for women). When stratified by both BMI and WC, 10-year mortality risk was significantly higher in patients with Low BMI/Low WC (adjusted hazard ratio [HR]: 1.65; 95% confidence interval [CI]: 1.09 to 2.51), Low BMI/ High WC (adjusted HR: 2.74; 95% CI: 1.12 to 6.69), or High BMI/High WC (adjusted HR: 1.59; 95% CI: 1.11 to 2.27) compared to those with High BMI/Low WC. In conclusion, the “obesity paradox” following coronary revascularization would be driven by low long-term mortality risk of the High BMI/Low WC group. Body composition should be assessed by the combination of BMI and WC in the appropriate evaluation of the long-term risk of obesity in patients with LMCAD or 3VD. Numerous studies have demonstrated a paradoxical association between higher baseline body mass index (BMI) and lower long-term mortality risk after coronary revascularization, known as the “obesity paradox”, possibly relying on the single use of BMI. The current study is a post-hoc analysis of the SYNTAX Extended Survival (SYNTAXES) trial, which is the extended follow-up of the SYNTAX trial comparing percutaneous coronary intervention (PCI) versus coronary artery bypass graft (CABG) in patients with left-main coronary artery disease (LMCAD) or three-vessel disease (3VD). Patients were stratified according to baseline BMI and/or waist circumference (WC). Out of 1,800 patients, 1,799 (99.9%) and 1,587 (88.2%) had available baseline BMI and WC data, respectively. Of those, 1,327 (73.8%) patients had High BMI (≥25 kg/m2), whereas 705 (44.4%) patients had High WC (>102 cm for men or >88 cm for women). When stratified by both BMI and WC, 10-year mortality risk was significantly higher in patients with Low BMI/Low WC (adjusted hazard ratio [HR]: 1.65; 95% confidence interval [CI]: 1.09 to 2.51), Low BMI/ High WC (adjusted HR: 2.74; 95% CI: 1.12 to 6.69), or High BMI/High WC (adjusted HR: 1.59; 95% CI: 1.11 to 2.27) compared to those with High BMI/Low WC. In conclusion, the “obesity paradox” following coronary revascularization would be driven by low long-term mortality risk of the High BMI/Low WC group. Body composition should be assessed by the combination of BMI and WC in the appropriate evaluation of the long-term risk of obesity in patients with LMCAD or 3VD. Obesity is a major health problem worldwide and contributes to progression of cardiovascular disease, including coronary artery disease (CAD), leading to poor prognosis.1Pischon T Boeing H Hoffmann K Bergmann M Schulze MB Overvad K van der Schouw YT Spencer E Moons KG Tjonneland A Halkjaer J Jensen MK Stegger J Clavel-Chapelon F Boutron-Ruault MC Chajes V Linseisen J Kaaks R Trichopoulou A Trichopoulos D Bamia C Sieri S Palli D Tumino R Vineis P Panico S Peeters PH May AM Bueno-de-Mesquita HB van Duijnhoven FJ Hallmans G Weinehall L Manjer J Hedblad B Lund E Agudo A Arriola L Barricarte A Navarro C Martinez C Quiros JR Key T Bingham S Khaw KT Boffetta P Jenab M Ferrari P Riboli E. General and abdominal adiposity and risk of death in Europe.N Engl J Med. 2008; 359: 2105-2120Crossref PubMed Scopus (1437) Google Scholar Nevertheless, numerous studies have demonstrated in patients undergoing percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) a paradoxical association between high baseline body mass index (BMI) and a low mortality risk, the so-called “obesity paradox”.2Lavie CJ McAuley PA Church TS Milani RV Blair SN. Obesity and cardiovascular diseases: implications regarding fitness, fatness, and severity in the obesity paradox.J Am Coll Cardiol. 2014; 63: 1345-1354Crossref PubMed Scopus (379) Google Scholar, 3Gruberg L Weissman NJ Waksman R Fuchs S Deible R Pinnow EE Ahmed LM Kent KM Pichard AD Suddath WO Satler LF Lindsay Jr., J The impact of obesity on the short-term and long-term outcomes after percutaneous coronary intervention: the obesity paradox?.J Am Coll Cardiol. 2002; 39: 578-584Crossref PubMed Scopus (470) Google Scholar, 4Schwann TA Ramia PS Engoren MC Bonnell MR Goodwin M Monroe I Habib RH. Evidence and temporality of the obesity paradox in coronary bypass surgery: an analysis of cause-specific mortality.Eur J Cardiothorac Surg. 2018; 54: 896-903Crossref PubMed Scopus (4) Google Scholar, 5Ono M Chichareon P Tomaniak M Kawashima H Takahashi K Kogame N Modolo R Hara H Gao C Wang R Walsh S Suryapranata H da Silva PC Cotton J Koning R Akin I Rensing B Garg S Wykrzykowska JJ Piek JJ Jüni P Hamm C Steg PG Valgimigli M Windecker S Storey RF Onuma Y Vranckx P Serruys PW. The association of body mass index with long-term clinical outcomes after ticagrelor monotherapy following abbreviated dual antiplatelet therapy in patients undergoing percutaneous coronary intervention: a prespecified sub-analysis of the GLOBAL LEADERS Trial.Clin Res Cardiol. 2020; 109: 1125-1139PubMed Google Scholar, 6Romero-Corral A Montori VM Somers VK Korinek J Thomas RJ Allison TG Mookadam F Lopez-Jimenez F. Association of bodyweight with total mortality and with cardiovascular events in coronary artery disease: a systematic review of cohort studies.Lancet. 2006; 368: 666-678Abstract Full Text Full Text PDF PubMed Scopus (1119) Google Scholar Although the exact biological and prognostic significance of the “obesity paradox” remains unclear thus far, one major hypothesis is that BMI itself would be a poor and indirect indicator of obesity-related cardiovascular risk since it does not necessarily reflect total body adiposity.7Iliodromiti S Celis-Morales CA Lyall DM Anderson J Gray SR Mackay DF Nelson SM Welsh P Pell JP Gill JMR Sattar N The impact of confounding on the associations of different adiposity measures with the incidence of cardiovascular disease: a cohort study of 296 535 adults of white European descent.Eur Heart J. 2018; 39: 1514-1520Crossref PubMed Scopus (78) Google Scholar Therefore, to combine BMI with other body composition indices such as waist circumference (WC) may achieve better predictive performance than single use of BMI, and may provide insights into the obesity paradox. The aim of the present subgroup analysis of the SYNTAX Extended Survival (SYNTAXES) study is to investigate the impact of body composition on very long-term clinical outcomes by using BMI and WC as two different anthropomorphic indices in patients with severe CAD who underwent PCI or CABG. The present study is a post-hoc subgroup analysis of the SYNTAXES study (NCT03417050), which was an investigator-driven extended 10-year follow-up of the SYNTAX trial (NCT00114972) beyond its original final follow-up of 5 years.8Serruys PW Morice MC Kappetein AP Colombo A Holmes DR Mack MJ Ståhle E Feldman TE van den Brand M Bass EJ Van Dyck N Leadley K Dawkins KD Mohr FW. Percutaneous coronary intervention versus coronary-artery bypass grafting for severe coronary artery disease.N Engl J Med. 2009; 360: 961-972Crossref PubMed Scopus (3050) Google Scholar,9Mohr FW Morice MC Kappetein AP Feldman TE Ståhle E Colombo A Mack MJ Holmes Jr., DR Morel MA Van Dyck N Houle VM Dawkins KD Serruys PW Coronary artery bypass graft surgery versus percutaneous coronary intervention in patients with three-vessel disease and left main coronary disease: 5-year follow-up of the randomised, clinical SYNTAX trial.Lancet. 2013; 381: 629-638Abstract Full Text Full Text PDF PubMed Scopus (1138) Google Scholar In brief, the SYNTAX trial was a multicenter, randomized controlled trial done in 85 hospitals across 18 North American and European countries. A total of 1,800 patients with de novo three-vessel disease (3VD) and/or left main CAD (LMCAD), who were deemed eligible for both PCI and CABG based on clinical judgement and the consensus of a Heart Team, were enrolled and randomized in a 1:1 fashion either to receive PCI (n = 903) with a uniform use of TAXUS Express paclitaxel-drug eluting stents (Boston Scientific Corporation, Marlborough, MA, USA) or CABG (n = 897). Patients who had only one of the two revascularization options were excluded from randomization and were entered into nested registries for PCI or CABG. The main result of the SYNTAXES study has been already reported.10Thuijs D Kappetein AP Serruys PW Mohr FW Morice MC Mack MJ Holmes Jr., DR Curzen N Davierwala P Noack T Milojevic M Dawkins KD da Costa BR Jüni P Head SJ Percutaneous coronary intervention versus coronary artery bypass grafting in patients with three-vessel or left main coronary artery disease: 10-year follow-up of the multicentre randomised controlled SYNTAX trial.Lancet. 2019; 394: 1325-1334Abstract Full Text Full Text PDF PubMed Scopus (187) Google Scholar Both SYNTAX and SYNTAXES trials were approved by the ethics committees at each investigating center, and all patients provided their written informed consent prior to participation in the SYNTAX trial. Follow-up was performed in accordance with local law and regulations of each participating institution and complied with the Declaration of Helsinki. Both BMI and WC measurements were collected at the time of randomization, prior to the index procedure. The patient's baseline BMI was calculated as weight in kilograms divided by height in meters squared. Patients were stratified according to their baseline BMI; Low BMI (<25 kg/m2) and High BMI (≥25 kg/m2) on the basis of World Health Organization and National Institutes of Health guidelines,11Jensen MD Ryan DH Apovian CM Ard JD Comuzzie AG Donato KA Hu FB Hubbard VS Jakicic JM Kushner RF Loria CM Millen BE Nonas CA Pi-Sunyer FX Stevens J Stevens VJ Wadden TA Wolfe BM Yanovski SZ. 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society.J Am Coll Cardiol. 2014; 63: 2985-3023Crossref PubMed Scopus (1210) Google Scholar in which patients with BMI ≥25 kg/m2 were classified as overweight (25.0 to 29.9 kg/m2) or obese (≥30 kg/m2). The patient's baseline WC was measured according to the protocol of the National Cholesterol Education Program (NCEP),12Mack MJ Banning AP Serruys PW Morice MC Taeymans Y Van Nooten G Possati G Crea F Hood KL Leadley K Dawkins KD Kappetein AP. Bypass versus drug-eluting stents at three years in SYNTAX patients with diabetes mellitus or metabolic syndrome.Ann Thorac Surg. 2011; 92: 2140-2146Abstract Full Text Full Text PDF PubMed Scopus (74) Google Scholar in which WC was measured at the level of the upper margin of the iliac crest. Patients were also stratified according to their baseline WC at the time of randomization; Low WC (≤102 cm [40 inches] for men or ≤88 cm [35 inches] for women) and High WC (>102 cm [40 inches] for men or >88 cm [35 inches] for women).11Jensen MD Ryan DH Apovian CM Ard JD Comuzzie AG Donato KA Hu FB Hubbard VS Jakicic JM Kushner RF Loria CM Millen BE Nonas CA Pi-Sunyer FX Stevens J Stevens VJ Wadden TA Wolfe BM Yanovski SZ. 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society.J Am Coll Cardiol. 2014; 63: 2985-3023Crossref PubMed Scopus (1210) Google Scholar,12Mack MJ Banning AP Serruys PW Morice MC Taeymans Y Van Nooten G Possati G Crea F Hood KL Leadley K Dawkins KD Kappetein AP. Bypass versus drug-eluting stents at three years in SYNTAX patients with diabetes mellitus or metabolic syndrome.Ann Thorac Surg. 2011; 92: 2140-2146Abstract Full Text Full Text PDF PubMed Scopus (74) Google Scholar Finally, patients were divided into 4 groups according to both baseline BMI and baseline WC; Low BMI/Low WC, Low BMI/High WC, High BMI/Low WC, and High BMI/High WC (Figure 1). Baseline hemoglobin A1c (HbA1c) and C-reactive protein (CRP) were analyzed in an independent central chemistry laboratory (Covance Incorporated, Indianapolis, US, and Geneva, Switzerland). The primary endpoint of the present study is all-cause death at 10 years. Vital status was confirmed by using electronic healthcare record review and national death registries. Patients with missing vital status were included in the analysis and censored at the time of “lost to follow-up” or at 5 years when recruiting centers did not participate in the SYNTAXES study for 10-year extended follow-up (a total of 5 patients in 2 centers). Continuous variables are expressed as median and interquartile range (IQR) and are compared using the Mann-Whitney U test. Categorical variables are presented as counts and percentage and are compared using chi-square test or Fisher's exact test as appropriate. Kaplan-Meier method is used to estimate the cumulative rates of events and log-rank test was performed to examine the differences between groups. A scatter plot was drawn between BMI and WC, and the Pearson correlation was used to quantify the relation between BMI and WC. The incidence of all-cause death up to 10 years was assessed in comparison either among BMI groups or WC groups using unadjusted and adjusted Cox proportional hazards models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). The covariables in the adjusted models included randomization (PCI or CABG), age, sex, medically treated diabetes, hypertension, dyslipidemia, current smokers, previous myocardial infarction (MI), previous cerebrovascular disease, peripheral vascular disease (PVD), chronic obstructive pulmonary disease (COPD), creatinine clearance, hemoglobin, left ventricular ejection fraction (LVEF), clinical presentation (silent ischemia, stable angina or unstable angina), achievement of complete revascularization, disease type (LMCAD or 3VD), and anatomical SYNTAX score. The estimated HRs were plotted for each observed pair BMI and WC values as a heat map. The reference for plotted HRs was the hazard at the median values of BMI and WC. For exploratory purposes, patients were also stratified according to their baseline BMI as follows; underweight/normal weight (≤24.9 kg/m2), overweight (25.0 to 29.9 kg/m2), and obesity (≥30 kg/m2).11 The primary endpoint of all-cause death was assessed in these BMI groups with or without WC as sensitivity analysis. Ten-year mortality was also assessed according to the waist-to-height ratio (WHtR) in the following subgroups: low WHtR (<0.50), intermediate WHtR (≥0.50 and <0.60), and high WHtR (≥0.60).13Ashwell M Hsieh SD. Six reasons why the waist-to-height ratio is a rapid and effective global indicator for health risks of obesity and how its use could simplify the international public health message on obesity.Int J Food Sci Nutr. 2005; 56: 303-307Crossref PubMed Scopus (587) Google Scholar Statistical significance was considered if two-sided p value ≤0.05. All analyses were performed in SPSS Statistics version 26 (IBM Corp., Armonk, 281 N.Y., USA) and R software version 3.5.1 (R Foundation for Statistical Computing, Vienna, Austria). Out of 1,800 patients, 1,799 patients (99.9%) had available baseline BMI data with a median value of 27.3 kg/m2 (IQR: 24.9 to 30.6 kg/m2). On the other hand, 1,587 patients (88.2%) had available baseline WC data with a median value of 98.0 cm (IQR: 90.0-106.7 cm). Among 1,799 patients with available BMI data, 472 (26.2%) and 1,327 patients (73.8%) were classified as Low BMI and High BMI, respectively. Whereas, among 1,587 patients with available WC data, 882 (55.6%) and 705 patients (44.4%) were classified as Low WC and High WC, respectively. When stratified by both BMI and WC, 344 (21.7%), 58 (3.7%), 538 (33.9%), and 647 patients (40.8%) were categorized as Low BMI/Low WC, Low BMI/High WC, High BMI/Low WC, and High BMI/High WC, respectively (Figure 1). The baseline characteristics in patients stratified by the combination of BMI and WC are shown in Table 1 and Online Table 1. When compared to patients with High BMI/Low WC, patients with High BMI/High WC were more frequently female, had a higher prevalence of medically treated diabetes as well as insulin dependant diabetes, metabolic syndrome and hypertension, had higher hemoglobin A1c (HbA1c) level and C-reactive protein (CRP) level, had lower creatinine clearance and LVEF, had higher EuroSCORE and Parsonnet SCORE, had lower number of lesions, had lower prevalence of any bifurcational lesions and took angiotensin-coverting enzyme inhibitor and angiotensin receptor blocker more frequently (all p <0.05). There was no significant difference in terms of age between patients with High BMI/Low WC and those with High BMI/High WC.Table 1Baseline characteristics in patients stratified by BMI and WCVariableLow BMIP valueHigh BMIP valueLow WC(N = 344)High WC(N = 58)Low WC(N = 538)High WC(N = 647)Body mass index (kg/m2)23.2 (21.9-24.2)23.6 (22.5-24.4)0.0827.3 (26.2-29.1)30.7 (28.3-33.6)<0.001Height (cm)171 (165-178)167 (160-178)0.028170 (166-175)170 (164-177)0.64Weight (kg)68.0 (62.0-73.0)64.6 (59.8-75.0)0.3381.0 (75.0-86.0)90.0 (80.0-100.0)<0.001Waist circumference (cm)87 (81-92)100 (92-104)<0.00194 (89-98)108 (104-115)<0.001Randomization0.480.68PCI50.9 (175/344)44.8 (26/58)50.4 (271/538)51.6 (334/647)CABG49.1 (169/344)55.2 (32/58)49.6 (267/538)48.4 (313/647)Age (year)67 (60-74)73 (67-78)<0.00165 (57-71)65 (58-72)0.85Sex<0.001<0.001 Male80.8 (278/344)37.9 (22/58)90.3 (486/538)67.9 (439/647) Female19.2 (66/344)62.1 (36/58)9.7 (52/538)32.1 (208/647)Medically-treated diabetes15.1 (52/344)29.3 (17/58)0.01320.1 (108/538)33.4 (216/647)<0.001 On insulin7.0 (24/344)6.9 (4/58)1.006.3 (34/538)14.7 (95/647)<0.001Hemoglobin A1c (%)5.8 (5.5-6.2)6.1 (5.6-6.7)0.0485.8 (5.5-6.2)6.0 (5.6-6.7)<0.001C-reactive protein (mg/dl)0.23 (0.09-0.80)0.33 (0.12-0.83)0.230.30 (0.11-0.73)0.42 (0.16-0.93)<0.001Metabolic syndrome15.9 (46/290)68.6 (35/51)<0.00124.6 (111/452)75.9 (415/547)<0.001Hypertension64.2 (221/344)67.2 (39/58)0.7763.2 (340/538)69.6 (450/647)0.022Dyslipidemia73.2 (251/343)75.4 (43/57)0.8779.3 (424/535)78.0 (497/637)0.62Current smoking26.8 (92/343)17.2 (10/58)0.1419.0 (102/537)18.4 (118/643)0.82Previous MI34.0 (116/341)46.6 (27/58)0.0829.5 (157/533)33.4 (213/638)0.16Previous cerebrovascular disease14.0 (48/343)15.5 (9/58)0.8413.2 (71/536)15.1 (97/643)0.40 Previous stroke3.5 (12/343)0.0 (0/58)0.233.7 (20/534)5.3 (34/644)0.26 Previous transient ischemic attack5.5 (19/343)6.9 (4/58)0.765.4 (29/537)4.1 (26/640)0.33 Previous carotid artery disease7.3 (25/344)8.6 (5/58)0.797.8 (42/538)9.1 (59/647)0.47Peripheral vascular disease10.5 (36/344)19.0 (11/58)0.088.4 (45/538)9.3 (60/647)0.61Chronic obstructive pulmonary disease6.4 (22/344)12.1 (7/58)0.167.6 (41/538)9.7 (63/647)0.22Chronic kidney disease36.5 (113/310)46.3 (25/54)0.1713.1 (64/489)13.6 (82/601)0.86Creatinine clearance (ml/min)69.0 (55.9-84.1)63.3 (51.8-74.2)0.00882.6 (68.0-101.1)91.3 (72.2-116.1)<0.001Left ventricular ejection fraction (%)60 (50-65)58 (44-63)0.1860 (55-70)60 (50-65)0.001Congestive heart failure3.8 (13/342)3.5 (2/57)1.004.5 (24/533)5.8 (37/637)0.36Clinical presentation0.620.99 Silent myocardial ischemia16.6 (57/344)20.7 (12/58)13.6 (73/538)13.8 (89/647) Stable angina pectoris52.9 (182/344)46.6 (27/58)58.6 (315/538)58.1 (376/647) Unstable angina pectoris30.5 (105/344)32.8 (19/58)27.9 (150/538)28.1 (182/647)EuroSCORE4 (2-6)6 (4-7)<0.0013 (1-5)4 (2-6)0.009Parsonnet SCORE5 (3-12)10 (4-19)<0.0016 (3-10)8 (6-14)<0.001Disease type0.250.72 3VD58.7 (202/344)67.2 (39/58)60.4 (325/538)61.5 (398/647) LMCAD41.3 (142/344)32.8 (19/58)39.6 (213/538)38.5 (249/647)Disease type0.320.09 LMCAD only4.7 (16/344)1.8 (1/57)3.9 (21/538)6.5 (42/647) LMCAD+1VD9.6 (33/344)3.5 (2/57)5.9 (32/538)7.9 (51/647) LMCAD+2VD14.0 (48/344)12.3 (7/57)12.1 (65/538)10.8 (70/647) LMCAD+3VD13.1 (45/344)15.8 (9/57)17.7 (95/538)13.3 (86/647) 2VD (No LMCAD)2.6 (9/344)0.0 (0/57)1.7 (9/538)2.0 (13/647) 3VD (No LMCAD)56.1 (193/344)66.7 (38/57)58.7 (316/538)59.5 (385/647)SYNTAX score29 (20-37)29 (21-38)0.7327 (21-37)27 (20-35)0.08SYNTAX score tercile0.940.23 Low30.7 (105/342)28.6 (16/56)30.2 (162/537)34.6 (223/644) Intermediate33.9 (116/342)35.7 (20/56)35.4 (190/537)34.3 (221/644) High35.4 (121/342)35.7 (20/56)34.5 (185/537)31.1 (200/644)Number of lesions4 (3-6)4 (3-6)0.604 (3-6)4 (3-5)0.007Any total occlusion22.9 (78/341)23.2 (13/56)1.0024.2 (130/537)23.5 (151/643)0.78Any bifurcation71.8 (245/341)75.0 (42/56)0.7576.5 (411/537)70.3 (452/643)0.018Number of stents4 (3-6)5 (4-7)0.525 (3-6)5 (3-6)0.81Total stent length per patient80 (48-117)88 (76-132)0.1282 (52-112)80 (52-112)0.88Off pump coronary bypass14.5 (23/159)21.9 (7/32)0.2914.2 (37/261)19.8 (60/303)0.09Complete revascularization59.5 (198/333)54.4 (31/57)0.4758.1 (309/532)61.2 (390/637)0.28Medication at discharge Any antiplatelet therapy Aspirin95.1 (312/328)94.5 (52/55)0.7493.6 (494/528)94.4 (594/629)0.54 Thienopyridine60.4 (198/328)49.1 (27/55)0.1459.7 (315/528)61.2 (385/629)0.63 Statin82.0 (269/328)78.2 (43/55)0.5782.2 (434/528)82.0 (516/629)1.00 Beta blocker78.7 (258/328)76.4 (42/55)0.7279.7 (421/528)83.6 (526/629)0.09 ACEI52.7 (173/328)43.6 (24/55)0.2447.7 (252/528)55.0 (346/629)0.015 ARB7.3 (24/328)18.2 (10/55)0.0188.5 (45/528)13.0 (82/629)0.018Data are presented as median (interquartile range) or percentage (number).ACEI: angiotensin-converting enzyme inhibitor; ARB: angiotensin receptor blocker; CABG: coronary artery bypass grafting; LMCAD: left main coronary artery disease; LVEF: left ventricular ejection fraction; MI: myocardial infarction; PCI: percutaneous coronary intervention; SYNTAX: Synergy between PCI with Taxus and Cardiac Surgery; 3VD: three-vessel disease. Open table in a new tab Data are presented as median (interquartile range) or percentage (number). ACEI: angiotensin-converting enzyme inhibitor; ARB: angiotensin receptor blocker; CABG: coronary artery bypass grafting; LMCAD: left main coronary artery disease; LVEF: left ventricular ejection fraction; MI: myocardial infarction; PCI: percutaneous coronary intervention; SYNTAX: Synergy between PCI with Taxus and Cardiac Surgery; 3VD: three-vessel disease. The scatterplot of BMI and WC is shown in Figure 2. There was a significant though modest correlation between BMI and WC (Pearson r coefficient 0.675; R2 0.46; p <0.001). The median durations of the 10-year were 3,653 days (interquartile range [IQR]: 2,796 to 3,653 days). At 10 years, the crude incidence of all-cause death was significantly lower in patients with High BMI compared with those with low BMI, however, after adjustment there was no longer significant difference between 2 groups (Figure 3 and Table 2). In contrast, patients with High WC had a significantly higher crude rate of all-cause death at 10 years compared with those with Low WC. The increased mortality risk in High WC over Low WC was consistent even after adjustment (Figure 3 and Table 2). As a continuous variable, WC was an independent predictor of 10-year mortality in adjusted models, whereas BMI was not independently associated with the mortality risk (Table 2).Table 2Adjusted hazard ratio for all-cause mortality at 10 years among normal weight, overweight, and obesity patientsUnadjusted HRP valueAdjusted HRP value(95% CI)(95% CI)*Adjusted covariates are randomization (PCI or CABG), age, sex, medically treated diabetes, hypertension, dyslipidemia, current smokers, previous myocardial infarction, previous cerebrovascular disease, peripheral vascular disease, chronic obstructive pulmonary disease, creatinine clearance (ml/min), hemoglobin (g/dl), left ventricular ejection fraction, clinical presentation (silent ischemia, stable angina or unstable angina), achievement of complete revascularization, disease type (LMCAD or 3VD), and anatomical SYNTAX score. Abbreviations as in Table 1.High BMI vs. Low BMI0.73 (0.60-0.88)0.0010.86 (0.64-1.15)0.312BMI (each 1 kg/m2 increase)0.99 (0.97-1.01)0.2671.01 (0.98-1.04)0.535High WC vs. Low WC1.30 (1.07-1.57)0.0081.45 (1.09-1.93)0.012WC (each 1 cm incrase)1.01 (1.00-1.01)0.0861.01 (1.00-1.03)0.012 Adjusted covariates are randomization (PCI or CABG), age, sex, medically treated diabetes, hypertension, dyslipidemia, current smokers, previous myocardial infarction, previous cerebrovascular disease, peripheral vascular disease, chronic obstructive pulmonary disease, creatinine clearance (ml/min), hemoglobin (g/dl), left ventricular ejection fraction, clinical presentation (silent ischemia, stable angina or unstable angina), achievement of complete revascularization, disease type (LMCAD or 3VD), and anatomical SYNTAX score.Abbreviations as in Table 1. Open table in a new tab When patients were divided into 4 groups by both BMI and WC, patients with High BMI/Low WC showed the lowest crude rate of death at 10 years (19.4%), followed by those with High BMI/High WC (29.7%), Low BMI/Low WC (31.7%), and Low BMI/High WC (38.6%) (Figure 4). After adjusting for potential confounders, the risks of all-cause death at 10 years were significantly higher in patients with Low BMI/Low WC, Low BMI/High WC, or High BMI/High WC compared to those with High BMI/Low WC (Figures 5 and 6). Online Table 2 presents the results in the variant adjusted models including different potential confounders, showing the consistency of the results. The heat map of adjusted risk for all-cause death at 10 years demonstrated that patients with higher BMI but lower WC had lower mortality risk, and in contrast, patients with lower BMI but higher WC had higher mortality risk (Figure 6).Figure 5Hazard ratios of all-cause death at 10 years. Adjusted covariates are listed in Table 2. HR: hazard ratio; CI: confidence interval; Other abbreviations as in Figure 1.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Figure 6Complementary relationship between BMI and WC in predicting the risk of 10-year mortality. In the heat map of adjusted risk for all-cause mortality at 10 years, “X” indicates the reference point (median value of BMI [27.3 kg/m2] and WC [98 cm]). Patients with higher BMI but lower WC (the bottom right area of the heat map) had lower mortality risk (bluer), and on the contrast, patients with lower BMI but higher WC (the upper left area of the heat map) had higher mortality risk (redder) at 10 years. When stratified by binary thresholds of BMI (< or ≥25 kg/m2) and WC (≤ or >102 cm in men or ≤ or >88 cm in women), patients with High BMI/Low WC had the lowest risk of all-cause death at 10 years, whereas the risk was significantly higher in patients with Low BMI/Low WC, Low BMI/High WC, or High BMI/High WC. The adjusted covariates are listed in Table 2. Abbreviations as in Figures 1 and 5.View Large Image Figure ViewerDownload Hi-res image Download (PPT) When stratified by revascularization mode, similar trends were observed either in PCI or CABG arm (Online Figure 1 and 2). The results according to BMI <25.0 kg/m2 (underweight or normal weight), 25.0 to 29.9 kg/m2 (overweight), or ≥30 kg/m2 (obesity), with combination of WC are presented in Online Figure 3 and 4. When compared to overweight patients with low WC, overweight patients with high WC had significantly higher risks of all-cause death at 10 years. There were no significant difference in all-cause death among those 3 WHtR groups (Online Figure 5). In our study, BMI had a modest correlation with WC (Figure 2), however, BMI and WC showed diverging and opposite associations with crude mortality rate at 10 years (Figure 3). When stratified by both BMI and WC, patients with High BMI/Low WC had the lowest crude 10-year mortality rate, which contributed to the favorable outcome of High BMI group (Figure 4). It can be assumed that the High BMI/Low WC patients might have more lean body mass including organs, bones, and muscle mass, than fat mass. In fact, patients with High BMI/Low WC were more frequently male (90.3%), were less frequently diabetes (especially on insulin), and had significantly lower levels of HbA1c and CRP, compared to those with High BMI/High WC (Table 1), indicating that the High BMI/High WC patients may be the “true obesity” group with more metabolic risks including insulin resistance and proinflammatory conditions, possibly contributing to the worse outcomes compared to High BMI/Low WC group.14Frank AP de Souza Santos R Palmer BF Clegg DJ. Determinants of body fat distribution in humans may provide insight about obesity-related health risks.J Lipid Res. 2019; 60: 1710-1719Abstract Full Text Full Text PDF PubMed Scopus (41) Google Scholar Recently, Beyhoff et al reported that increased high-sensitivity CRP (hsCRP) level was associated with increase in BMI from normal weight toward severely obese in patients undergoing PCI,15Beyhoff N Cao D Mehran R Dangas G Baber U Sartori S Blum M Roumeliotis A Chandiramani R Goel R Zhang
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