Body mass index and prognostic outcomes after transcatheter aortic valve replacement: Insights from the Chinese Cardiovascular Association Database-National Transcatheter Valve Therapeutics Registry

To the Editor: Transcatheter aortic valve replacement (TAVR) has witnessed a rapid global surge and emerged as a viable alternative for treating aortic stenosis patients. Obesity, a well-established risk factor for the development of cardiovascular diseases, significantly contributes to disease burden. Research on TAVR patients, predominantly from Western nations, has highlighted a decreased risk associated with overweight or obesity,[1–3] which is known as the “obesity paradox” phenomenon. However, the body mass index (BMI) of East Asian patients undergoing TAVR is notably lower than that of Western countries.[4] Consequently, the BMI–mortality relationship seen in Western countries may not be directly applicable to Asia. We aim to examine both categorical and dose-response associations between BMI and prognostic outcomes in patients undergoing TAVR within a Chinese national cohort. The Chinese Cardiovascular Association (CCA) Database–National Transcatheter Valve Therapeutics Registry (NTCVR) serves as a dynamic cohort of patients undergoing valve intervention.[5] Up to July 2023, it has included 138 centers from 26 provinces in China. Demographic characteristics, clinical data, image evaluation, procedural specifics, and post-procedure events were collected. Follow-up visits were conducted at 1 month, 3 months, and 1 year by clinic visit or telephone call. The approval for the study was granted by the Medical Ethics Committee of the Second Affiliated Hospital of Zhejiang University, with patient consent being waived due to the retrospective nature. A total of 6531 patients who underwent TAVR procedure were included in the analysis [Supplementary Figure 1, https://links.lww.com/CM9/C197] and were then categorized into four groups according to the Chinese guideline:[6] underweight (BMI <18.5 kg/m2), normal weight (18.5 ≤ BMI <24.0 kg/m2), overweight (24.0 ≤ BMI <28.0 kg/m2), and obese (BMI ≥28.0 kg/m2) groups. The overall follow-up rate was 73.0% (6576/9013) and the average follow-up time was 200 days. The primary endpoint was 1-year mortality, while secondary outcomes included (1) 30-day mortality and (2) in-hospital events, comprising device failure, major vascular complications, life-threatening or major bleeding, postprocedural moderate/severe perivalvular aortic regurgitation (AR), permanent pacemakers, atrial fibrillation, stroke, and myocardial infarction (MI). Periprocedural events were defined according to Valve Academic Research Consortium (VARC)-2 criteria.[7] Detailed methods are described in the Supplementary Material, https://links.lww.com/CM9/C197. The mean age was 73.6 years, with 3869 (59.2%) of them being men. In total, 8.3% (n = 544), 56.8% (n = 3708), 27.2% (n = 1778), and 7.7% (n = 501) patients were underweight, normal-weight, overweight, and obese, respectively. Baseline demographics, clinical characteristics, and echocardiography parameters differed by BMI categories [Supplementary Table 1, https://links.lww.com/CM9/C197]. A total of 285 deaths were documented within the 1-year follow-up. The 1-year mortality was greater in the underweight group than other BMI categories (P <0.001, Supplementary Figure 2, https://links.lww.com/CM9/C197). The landmark analysis also revealed that the mortality rate was the highest in underweight patients among those who survived more than 30 days [Supplementary Figure 3, https://links.lww.com/CM9/C197]. Restricted cubic spline (RCS) analysis showed a non-linear dose-response relationship between BMI and 1-year mortality. There was a sharp decrease in the risk of 1-year mortality before approximately 25.0 kg/m2, after which the risk became relatively stable (P for non-linearity = 0.041, Supplementary Figure 4, https://links.lww.com/CM9/C197). According to both the univariate and the multivariate Cox regression models, the risk of 1-year mortality was higher for underweight patients compared with normal-weight patients, but not for overweight or obese individuals. With normal weight as the reference, the adjusted HRs (95% CIs) were 1.78 (1.26–2.51), 0.84 (0.62–1.14), and 1.16 (0.74–1.82) for underweight, overweight, and obese subjects, respectively [Supplementary Table 2, https://links.lww.com/CM9/C197]. A total of 204 deaths were reported within the 30-day follow-up. The 30-day mortality risk was the highest in the underweight group [Supplementary Figure 5, https://links.lww.com/CM9/C197]. The shape of the RCS curve regarding the 30-day mortality risk and BMI resembled that of the 1-year mortality; however, the test for non-linearity was non-significant (P for non-linearity = 0.371, Supplementary Figure 6, https://links.lww.com/CM9/C197). After adjusting for potential confounders, underweight individuals faced an increased risk of 30-day mortality (HR, 1.53; 95% CI: 1.01–2.33) compared with normal-weight patients. No significant difference was observed between overweight (HR, 0.85; 95% CI: 0.60–1.21) or obese (HR, 1.02; 95% CI: 0.58–1.78) patients and those of normal-weight [Supplementary Table 3, https://links.lww.com/CM9/C197]. Inverse probability weighting analysis of in-hospital adverse outcomes comparing different BMI groups is shown in Supplementary Table 4, https://links.lww.com/CM9/C197. Compared with normal-weight individuals, the risk of major vascular complications was significantly increased in the obese group (odds ratio [OR], 2.99; 95% CI: 1.33–6.19), but did not reach statistical significance in the underweight (OR, 2.02; 95% CI: 0.80–4.46) and overweight (OR, 1.22; 95% CI: 0.61–2.34) groups. Underweight and obese groups had higher risk of life-threatening or major bleeding compared with normal-weight patients, with the ORs (95% CIs) of 2.43 (1.21–4.56) and 3.37 (1.78–6.10), respectively. There was significantly greater risk of atrial fibrillation in underweight patients compared with normal-weight patients (OR, 2.00; 95% CI: 1.19–3.22). No significant differences in the risk of device failure, postprocedural moderate/severe perivalvular AR, permanent pacemaker, stroke and MI across BMI categories were observed. Subgroup analyses indicated that left ventricular ejection fraction (LVEF) categories modified the association between BMI categories and 1-year mortality (P for interaction = 0.019), with the association being significant only for underweight patients with LVEF ≥50% [Supplementary Table 5, https://links.lww.com/CM9/C197]. Sensitivity analyses did not change the results markedly and showed the robustness of our main findings [Supplementary Tables 6 and 7, https://links.lww.com/CM9/C197]. In this national cohort, we found a rapid decrease in the 1-year mortality risk with increasing BMI until approximately 25.0 kg/m2, after which it leveled. The 1-year mortality risk for normal-weight patients was significantly lower than that for underweight patients but was similar to that for their overweight and obese counterparts. The risks of in-hospital major vascular complication and major bleeding were greater in the obese group than in the normal-weight group. Compared with normal weight, underweight was associated with a greater risk of 30-day mortality, in-hospital life-threatening or major bleeding, and in-hospital atrial fibrillation. Our investigation into Chinese patients undergoing TAVR revealed a markedly higher prevalence of underweight individuals and a lower rate of obesity than studies from Western countries. In our research, 8.3% of the patients had a BMI <18.5 kg/m2 whereas 7.7% had a BMI ≥28.0 kg/m2. In contrast, the French national FRANCE 2 registry reported that only 3.1% of the patients had a BMI <18.5 kg/m2, and 18.6% had a BMI >30.0 kg/m2.[8] Similarly, in the US national Registry, 2.5% had a BMI <18.5 kg/m2 while 30.3% had a BMI ≥30.0 kg/m2.[3] Previous meta-analyses indicated a reduced risk of mortality associated with overweight and obesity among TAVR patients; however, nearly all of the studies included were from Western countries.[1,2] In contrast, this study from Chinese patients and a report from Japan did not find an “obesity paradox” following TAVR.[4] The discrepancy might stem from racial differences in the BMI–mortality risk association. Given that visceral adipose tissue is more detrimental than subcutaneous fat, and that Asians tend to accumulate more visceral fat than non-Asians, it is logical that obese Asians experience fewer survival benefits. However, studies with more patients might be needed to confirm this, since the point estimates of the effects from these two studies (0.84 and 0.71) were below 1.00. Despite the similar mortality risk to normal-weight TAVR patients, obese subjects had a higher risk of major vascular complications in our study, keeping in line with previous findings.[1,2] One reason for this is the preferred femoral approach due to its lower procedural risk and the substantial distance from the skin to the femoral artery. Performing TAVR needs caution when dealing with vascular access in obese patients. We also found an increased risk of life-threatening or major bleeding associated with obesity, inconsistent with previous evidence.[1,2] The discrepancy might be due to racial difference or the in-hospital medical treatment; further studies were needed to verify this. Few articles studied mortality risk in underweight patients undergoing TAVR, with small sample sizes and inconsistent findings.[2] Our data comprised a relatively substantial proportion of underweight patients and illustrated that those who were underweight faced an increased risk of both short-term and long-term mortality. The elevated long-term mortality among underweight patients undergoing TAVR might be attributed to potential confounding by frailty- or cachexia-related conditions. However, in the context of acute MI, the increased mortality risk associated with underweight persisted even after thorough adjustment for comorbidities and frailty measures, suggesting underweight as an independent risk factor.[9] This increased long-term mortality associated with underweight could also be due to diminished physiologic reserves and fat stores in underweight individuals, potentially compromising their ability to endure health challenges over time.[9] The increased short-term mortality risk among underweight patients might be attributed to a higher rate of in-hospital complications. Consistent with previous findings, we observed that underweight patients experienced more life-threatening or major bleeding compared with those with normal weight.[2] Since postprocedural platelet inhibitions were widely administered after TAVR, higher bleeding might be a consequence of affected drug metabolisms and thus higher drug concentrations in underweight patients. In our study, underweight patients were at greater risk of postprocedural atrial fibrillation, but previous studies found no such association;[4,10] the difference might be explained by the small sample size of prior studies, and additional studies are needed. Since underweight TAVR patients had increased risks of mortality and in-hospital adverse events, it is crucial to carefully evaluate underweight patients and treat the underlying comorbidities. It will also be of considerable interest to examine whether interventions to promote weight gain in the underweight can ameliorate the adverse effects. Given the higher prevalence of underweight among Asians undergoing TAVR, the impact of survival disadvantage associated with underweight status may be particularly serious for Asian countries. To our knowledge, this study stands as the largest to analyze the association of BMI and prognostics among Asian TAVR patients. However, this study had several limitations. First, being observational, despite efforts to adjust for various covariates, the presence of unmeasured confounding factors cannot be considered. Second, physical indicators other than BMI, such as body composition measures and subcutaneous fat accumulation, might present the underlying reason for the BMI–mortality association after TAVR; however, our database lacked this information. Third, our analysis relied solely on baseline BMI data, precluding examination of temporal trend or changes in BMI post-TAVR, which could influence the mortality risk. In conclusion, in patients who underwent TAVR, underweight status was related to a significantly higher risk of both long-term and short-term mortality, while overweight or obese patients exhibited a mortality risk similar to that of their normal-weight counterparts. This study did not find evidence supporting the “obesity paradox” among Asian patients undergoing TAVR and emphasized the importance of carefully evaluating underweight patients. Funding The study was granted by Healthy Zhejiang One Million People Cohort (No. K-20230085). Conflicts of interest None.