Abstract
Background
Obesity is a major risk factor for cardiovascular morbidity and mortality. A considerable number of studies, however, showed better outcomes for overweight patients undergoing cardiovascular interventions—the so called obesity paradox.
Hypothesis
Increased body mass index (BMI) is independently associated with improved survival following transcatheter aortic valve implantation (TAVI).
Methods
We analyzed the data of 409 consecutive patients undergoing TAVI in our medical center. Patients were categorized into 4 groups according to BMI: underweight (≤18.4 kg/m2), normal weight (18.5–24.9 kg/m2), overweight (25–29.9 kg/m2), and obese (≥30 kg/m2). Procedure‐related complications were recorded, as well as 30‐day and 1‐year all‐cause mortality rates.
Results
Obese patients had a higher prevalence of comorbidities and higher incidence of vascular complications compared with the normal‐weight patients (16% vs 7%, P = 0.013). Nevertheless, 30‐day mortality was similar among the groups, whereas 1‐year mortality was lower among the overweight and obese patients (BMI >25) (P = 0.038). After adjusting for differences in baseline characteristics, increase in BMI was found to be independently associated with improved survival following TAVI (hazard ratio: 0.94, confidence interval: 0.89‐0.99, P = 0.043).
Conclusions
In our single‐center study, obesity and overweight were independently associated with better outcome, supporting the obesity paradox in the TAVI population.
Introduction
Obesity is a major modifiable risk factor for cardiovascular morbidity and mortality.1 Nevertheless, a considerable number of studies showed better outcomes for overweight and obese patients after percutaneous and surgical cardiovascular interventions in general, and after surgical aortic valve replacement in particular.2, 3, 4, 5, 6, 7 This phenomenon was termed the obesity paradox, and its validity is still under discussion in the literature. Although several studies demonstrated a protective or beneficial effect of overweight and obese patients undergoing percutaneous coronary intervention (PCI) or heart surgery,3, 7, 8, 9, 10 other studies showed no such protective effect, and even showed a detrimental effect of overweight patients compared with normal weight patients.11, 12, 13, 14 Investigators against the validity of the obesity paradox argue that the obese population is younger, seeks medical care earlier, is treated medically more aggressively, and therefore benefits more from medical and interventional treatment.15
Considering the well‐documented association between obesity and cardiovascular morbidity and mortality,16, 17, 18 and the expanding nature of obesity as an endemic healthcare problem, it is reasonable to expect an increasing number of obese patients with severe aortic stenosis being referred for transcatheter aortic valve implantation (TAVI).
In the present study we analyzed the effect of body mass index (BMI) on outcomes of elderly high‐risk patients with severe aortic valve stenosis undergoing transfemoral TAVI, and examined the validity of the obesity paradox in this population.
Methods
Study Population
The data for the present study were prospectively collected in the period between March 2009 and October 2013 at the Interventional Cardiology Unit of the Tel Aviv Medical Center, Tel Aviv, Israel. Informed consent was obtained from each patient as approved by the institutional ethics committee. The diagnosis of severe aortic valve stenosis was based on clinical, echocardiographic and hemodynamic criteria.19 Suitability and eligibility for TAVI was determined by our heart team. During the study period, 414 consecutive patients undergoing transfemoral TAVI were enrolled. As 5 patients did not have valid data for the determination of BMI at baseline, they were eliminated from the analysis, resulting in a final study population of 409 patients.
TAVI Procedure
TAVI was performed under general or local anesthesia. Two types of aortic valve prostheses were routinely implanted: the CoreValve aortic valve prosthesis (Medtronic, Inc., Minneapolis, MN) (26, 29, or 31 mm) and the Edwards SAPIEN XT prosthesis (Edwards Lifesciences Corp, Irvine, CA) (23 or 26 mm). One senior interventional cardiologist was responsible for all aspects of each case. Valve type and size were planed prior to the procedure according to preprocedural echocardiographic and angiographic parameters. Any complication, including bleeding and vascular complications were recorded during or shortly after the procedure. Bleeding events and vascular complications were classified as minor, major, and life threatening according to the Valve Academic Research Consortium classification.20 Data on red blood cell (RBC) transfusions were recorded by the institution's blood bank laboratory.
Body Mass Index
BMI was defined as the weight in kilograms divided by the square of the height in meters. The weight and height of all patients were collected at hospital admission before the TAVI procedure. Classification of the BMI was based on the World Health Organization (WHO) and National Institutes of Health guidelines and defined as underweight (≤18.4 kg/m2), normal weight (18.5 to 24.9 kg/m2), overweight (25.0 to 29.9 kg/m2), or obese (≥30 kg/m2).21 As there were only 5 (1%) patients classified as underweight, we ignored this group of patients when comparing outcomes of the procedure among different BMI groups.
Follow‐up and Mortality
After hospital discharge, all patients came for follow‐up visits at a dedicated TAVI clinic at 1 month, 6 months, and 1 year. Mortality data were collected by contacting the civil registries and the referring physician, and was complete in all patients who survived the first 30 days.
Clinical Outcomes
Primary end points were all‐cause mortality rates at 30 days and 1 year post‐TAVI. Secondary end points of the study were all procedure‐related complications, including major and life‐threatening bleeding events, vascular complications, blood transfusions, cerebrovascular events, and need for permanent pacemakers following the procedure.
Association Between Clinical Outcomes and BMI
As the aim of the study was to evaluate the impact of BMI on TAVI outcomes, we first compared procedure‐related complications between the different BMI groups, then we analyzed the correlation between mortality and BMI as a continuous variable. Finally, we compared the mortality rates between patients with normal weight (BMI ≤24.9 kg/m2) to patient defined as overweight or obese (BMI >25 kg/m2).
Statistical Analysis
All data were displayed as mean (±standard deviation) for continuous variables, and as the number (percentage) of patients in each group for categorical variables. The Student t test or analysis of variance test was used to evaluate the statistical significance between continuous variables; whereas the χ2 test was used in case categorical variables, respectively. Odds ratios were calculated with a confidence interval of 95%. To analyze the association between BMI and mortality, we performed a multivariate Cox proportional hazard model adjusting to all baseline clinical characteristics that were found to be significantly different among the BMI categories. The analysis was done for BMI as continuous as well as categorical variable (BMI < or ≥ 25 kg/m2). All of the analyses were considered significant at a 2‐tailed P value of <0.05. The SPSS statistical package (SSPS Inc., Chicago, IL) was used to perform all statistical evaluations.
Results
The final study cohort included 409 patients (41% males) at a mean age of 82 ± 5.7 years (range, 61–98 years). A high prevalence of comorbidities, cardiovascular risk factors, and prior vascular disease was observed in addition to the underlying valvular disorder, with 88% of patients suffering from hypertension, 34.5% from diabetes, and 59% from coronary artery disease. Mean logistic calculated EuroSCORE for the entire cohort was 24 ± 14, and 95% of patients were classified as New York Heart Association class III–IV. A CoreValve prosthesis was used in 75% of patients. The clinical characteristics of patients according to their BMI classification are presented in Table 1. According to the WHO classification, 5 (1%) patients were defined as underweight, 132 (32.5%) patients had normal weight, 169 (41.5%) were defined as overweight, and 102 (25%) were obese. As shown in Table 1, significant differences in baseline characteristics were found among the groups. The obese population was younger, had a higher prevalence of comorbidities, including diabetes mellitus, hypertension, and chronic obstructive pulmonary disease (P < 0.03 for all), whereas the logistic EuroSCORE for the obese group was lower. No differences were seen in the procedural details among the different BMI categories, including valve type and size.
Table 1.
Baseline Clinical Characteristics of Patients According to BMI Classification
| Variable | Entire Cohort, 409 Patients | 18.5 < BMI ≤ 24.9, Normal Weight, 132 Patients | 25 ≤ BMI ≤ 29.9, Overweight, 169 Patients | BMI ≥ 30, Obese, 102 Patients | P Value |
|---|---|---|---|---|---|
| Age, y, mean ± SD | 82 ± 5.7 | 84 ± 6 | 83 ± 5 | 80.5 ± 6 | 0.01 |
| Gender (male), n (%) | 173 (42) | 54 (41) | 83 (50) | 31 (30) | 0.01 |
| Diabetes mellitus, n (%) | 141 (34.5) | 34 (26) | 58 (34) | 47 (46) | 0.005 |
| Hypertension, n (%) | 359 (88) | 109(81) | 152 (90) | 95 (93) | 0.012 |
| Dyslipidemia, n (%) | 320 (78) | 100 (75) | 132 (78) | 84 (82) | 0.41 |
| Smoking, ever, n (%) | 105 (26) | 32 (24) | 40 (24) | 31 (30) | 0.42 |
| PVD, n (%) | 39 (7) | 14 (12) | 11 (6) | 4 (4) | 0.137 |
| CAD, n (%) | 240 (59) | 79 (59) | 102 (60) | 59 (56) | 0.73 |
| GFR (MDRD) (mL/min/1.73 m2), mean ± SD | 61 ± 19 | 62 ± 19 | 65 ± 20 | 56 ± 17 | <0.01 |
| Atrial fibrillation, n (%) | 121 (30) | 46 (35) | 42 (25) | 32 (30) | 0.17 |
| Prior stroke, n (%) | 41 (10) | 13 (10) | 16 (10) | 10 (10) | 0.99 |
| COPD, n (%) | 79 (19) | 21 (16) | 28 (17) | 30 (29) | 0.015 |
| Previous PCI, n (%) | 176 (43) | 59 (45) | 75 (45) | 41 (41) | 0.65 |
| Previous MI, n (%) | 69 (17) | 29 (22) | 23 (14) | 15 (15) | 0.12 |
| CABG, n (%) | 70 (17) | 23 (17) | 36 (21) | 11 (11) | 0.08 |
| NYHA class, n (%) | 271 (67) | 72 (54.5) | 130 (48) | 66 (65) | |
| III | |||||
| IV | 117 (29) | 55 (42) | 29 (17) | 31 (31) | <0.01 |
| EuroSCORE, mean ± SD | 24 ± 14 | 27 ± 14 | 23.5 ± 14 | 22 ± 13 | 0.01 |
| Aortic valve area, cm2, mean ± SD | 0.7 ± 0.2 | 0.65 ± 0.2 | 0.7 ± 0.1 | 0.76 ± 0.2 | 0.073 |
| Ejection fraction, %, mean ± SD | 55.8 ± 7.6 | 54.1 ± 8.6 | 56.8 ± 6.6 | 56.4 ± 7.5 | 0.058 |
| Valve type (Corevalve), n (%) | 308 (75) | 102 (77) | 127 (76) | 76 (74.5) | 0.8 |
Abbreviations: BMI, body mass index; CABG, coronary artery bypass graft; CAD, coronary artery disease; COPD, chronic obstructive pulmonary disease; GFR (MDRD), glomerular filtration rate (modification of diet in renal disease); MI, myocardial infarction; NYHA, New York Heart Association; PCI, percutaneous coronary intervention; PVD, peripheral vascular disease; SD, standard deviation.
In‐hospital outcomes are summarized in Table 2. Among the obese group, there was a higher prevalence of major vascular complications (16% vs 6% and 7% in the obese, overweight, and normal weight groups, respectively; P = 0.013), and a trend toward more major and life‐threatening bleeding events and need for permanent pacemakers. Despite higher rates of vascular complications and bleeding among patients classified as obese, blood transfusions were significantly more common among the normal‐weight group (49% vs 31% and 35% in the normal, overweight, and obese groups respectively; P = 0.01).
Table 2.
Clinical Outcomes According to BMI Classification
| Entire Cohort, 409 Patients | BMI ≤ 24.9, Normal Weight, 132 Patients | 25 ≤ BMI ≤ 29.9, Overweight, 169 Patients | BMI ≥ 30, Obese, 102 Patients | P Value | |
|---|---|---|---|---|---|
| Vascular complications, n (%) | 35 (9) | 9 (7) | 10 (6) | 16 (16) | 0.013 |
| Major/life threatening bleeding, n (%) | 53 (15) | 12 (11) | 21 (13) | 20 (22) | 0.055 |
| Blood transfusions, n (%) | 133 (37.5) | 55 (49) | 48 (31) | 30 (35) | 0.01 |
| New atrial fibrillation, n (%) | 28 (7) | 10 (7.5) | 10 (6) | 8 (8) | 0.78 |
| New pacemaker, n (%) | 86 (21) | 24 (17.5) | 32 (18) | 30 (30) | 0.067 |
| Acute kidney injury, n (%) | 49 (12) | 16 (12) | 20 (12) | 13 (13) | 0.96 |
| Cerebral ischemic event, n (%) | 22 (5.4) | 6 (4) | 11 (6) | 5 (5) | 0.71 |
Abbreviations: BMI, body mass index.
Mean follow‐up time was 542 ± 390 days. During the follow‐up period a total of 81 patients died, whereas 52 patients died within 1 year of the procedure. Regarding the association between BMI and mortality, when comparing patients with BMI ≤24.9 kg/m2 to overweight and obese patients (BMI >25 kg/m2), increased BMI was associated with reduced 1‐year mortality (odds ratio [OR]: 0.54, 95% confidence interval [CI]: 0.29‐0.99, P = 0.048). There was no association between BMI and 30‐day mortality rates (OR: 0.98, 95% CI: 0.94‐1.02, P = 0.4).
To analyze the independent impact of BMI on long‐term mortality, a multivariate Cox proportional hazard model was performed, adjusting for all clinical parameters that were found to be significantly different at baseline among the different BMI categories. BMI as a categorical variable (24.9 and below, 25 and above) was independently associated with long‐term mortality by COX regression analysis adjusted to baseline characteristics (hazard ratio [HR]: 0.60, 95% CI: 0.37‐0.97, P = 0.041); an increase in BMI was associated with improved survival (Figure 1), and BMI as a continuous variable was also found to be independently associated with mortality (HR: 0.94, 95% CI: 0.89‐0.99, P = 0.043 for every increase of 1 kg/m2 of BMI) (Table 3).
Figure 1.
Cox regression survival curve for patients with body mass index (BMI) ≤24.9 vs overweight and obese patients (BMI > 25) following transcatheter aortic valve implantation.
Table 3.
Multivariate Cox Proportional Hazard Model (BMI as Continuous Variable)
| Variable | Hazard Ratio | Confidence Interval | P Value |
|---|---|---|---|
| Gender | 0.71 | 0.45‐1.14 | 0.16 |
| Age | 1.03 | 0.98‐1.08 | 0.15 |
| Diabetes mellitus | 1.16 | 0.72‐1.87 | 0.53 |
| Hypertension | 1.41 | 0.66‐3.00 | 0.36 |
| COPD | 1.63 | 0.96‐2.78 | 0.07 |
| GFR (MDRD) | 0.99 | 0.97‐1.00 | 0.13 |
| EuroSCORE | 1.02 | 1.01‐1.04 | <0.001 |
| BMI | 0.94 | 0.89‐0.99 | 0.043 |
| NYHA class IV | 1.15 | 0.69‐1.90 | 0.59 |
Abbreviations: BMI, body mass index; COPD, chronic obstructive pulmonary disease, GFR (MDRD), glomerular filtration rate (modification of diet in renal disease); NYHA, New York Heart Association.
Discussion
Our single‐center study aimed to evaluate the association between BMI and TAVI outcomes, and to analyze the validity of the so called obesity paradox among this specific patients subset. The main finding of our study was that patients defined as overweight and obese had lower long‐term mortality rates despite higher incidence of procedure‐related complication.
Obesity has become an increasingly common chronic condition that is associated with significant morbidity and mortality.17, 22, 23 It has also been characterized as a major and modifiable risk factor for cardiovascular morbidity and mortality by the American Heart Association/American College of Cardiology and the Nutrition Council of the American Heart Association.1 However, a considerable number of studies reported a beneficial effect of overweight and obesity on survival in patients with established heart disease in general and in patients undergoing PCI or cardiac surgery in particular.7, 8, 9, 15 These provocative reports challenge the current guidelines advising weight loss and prevention of obesity, and may create the impression that a purposeful weight loss may not always be beneficial.
The relationship between TAVI outcomes and BMI is of particular interest considering the fact that TAVI is a procedure designed for patients who are poor candidates for aortic valve replacement due to their high prevalence of comorbidities, including obesity.
Our results are different from those reported previously by van der Boon et al, who retrospectively analyzed the impact of BMI on TAVI outcomes in 944 patients taking part in the PRAGMATIC Plus (Pooled‐RotterdAm‐Milano‐Toulouse In Collaboration) registry.24 According to this multicenter study, obesity was associated with a decrease in 30‐day mortality, but had no effect on long‐term outcomes, underscoring the obesity paradox. Furthermore, in contrast to our findings, they reported no increase in procedure‐related complications among the obese group. In our study, despite an increase in periprocedural complications, we found no increase in 30‐day mortality, indicating that the obese might survive better, even when confronting a higher prevalence of procedure‐related complications. A possible explanation might be that excess body weight may increase metabolic reserve and counteract the negative effects of acute morbidities.
Interestingly, patients in the obese group received RBC transfusion less frequently. This finding is not at all trivial considering the increased number of procedure‐related complications among this group, and the fact that hemoglobin level at admission was similar among all groups. We speculate that as these patients are perceived as less fragile by the treating staff, the therapeutic approach regarding blood transfusion in cases of anemia without overt bleedings was more restrictive, and therefore, overall, patients defined as obese were treated with RBC transfusion less frequently.
In our study, BMI as a categorical and continuous variable, was independently associated with long‐term survival. In fact, for every increase of 1 kg/m2 of BMI, the risk of mortality decreased by 6%. This finding is consistent with other studies supporting the obesity paradox2, 4, 5, 7, 25, 26, 27 and also consistent with the recent analysis from the FRANCE‐2 (French Aortic National CoreValve and Edwards 2) registry,28 according to which, among the TAVI population, overweight and obesity were associated with improved 1‐year survival despite higher rates of vascular complications.
Several possible explanations can be suggested for the obesity paradox. First, the fact that the obese group consisted of younger individuals, might have biased the findings. However, BMI remained an independent predictor of improved survival after adjusting to age and other cardiovascular risk factors in our study. Second, it is possible that overweight and obese patients are treated more aggressively with cardioprotective drugs that may contribute to better outcomes. Third, considering the association between blood transfusion and mortality following TAVI, which was proposed in several recent reports,29, 30, 31 it is plausible that the obese patients, treated significantly less frequently with RBC transfusions, present better long‐term survival.
This study has several limitations. First, although our data were obtained from a prospectively collected database, we conducted an observational, retrospective, and non‐prespecified analysis, and therefore, our results are subject to the effects of possible confounders by the nature of this design (eg, lack of data regarding clinical conditions that might influence both BMI and outcome such as active malignancy and overestimation of “dry” body weight due to fluid overload in TAVI candidates). Second, our cohort included only 5 patients defined as underweight, precluding us from studying the previously reported association between underweight and mortality following PCI and heart surgery27, 32 among the TAVI population. Third, a number of variables that might confound the outcomes (eg, drug therapy and frailty) were not available for analysis and might have affected the results of the multivariate analysis and its interpretation. Finally, as data regarding waist circumference and waist to hip ratio as indicators of obesity were not available, we used BMI as the only index of obesity. This may have resulted in a less‐accurate obesity grade determination.
Conclusion
In our single center study, obesity and overweight were independently associated with better outcome, supporting the obesity paradox in the TAVI population.
The authors have no funding, financial relationships, or conflicts of interest to disclose.
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