Clinical Investigations The Obesity Paradox in Patients Undergoing Transcatheter Aortic Valve Implantation Maayan Konigstein, MD; Ofer Havakuk, MD; Yaron Arbel, MD; Ariel Finkelstein, MD; Eyal Ben-Assa, MD; Eran Leshem Rubinow, MD, MHA; Yigal Abramowitz, MD; Gad Keren, MD; Shmuel Banai, MD
Address for correspondence: Maayan Konigstein, MD, Department of Cardiology, Affiliated to the Sackler School of Medicine, Tel Aviv University, Tel Aviv Medical Center, 6 Weitzman Street , Tel Aviv 64239, Israel [email protected]
Department of Cardiology, Tel-Aviv Medical Center, and the Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel
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 – 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 – 10 other studies showed no such protective effect, and even showed a detrimental effect of overweight patients compared with normal weight patients.11 – 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
The authors have no funding, financial relationships, or conflicts of interest to disclose.
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Clin. Cardiol. 38, 2, 76–81 (2015) Published online in Wiley Online Library (wileyonlinelibrary.com) DOI:10.1002/clc.22355 © 2015 Wiley Periodicals, Inc.
Considering the well-documented association between obesity and cardiovascular morbidity and mortality,16 – 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 Received: August 24, 2014 Accepted with revision: October 8, 2014
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 25 kg/m2 ), increased BMI was associated Clin. Cardiol. 38, 2, 76–81 (2015) M. Konigstein et al: Effect of BMI on TAVI outcomes Published online in Wiley Online Library (wileyonlinelibrary.com) DOI:10.1002/clc.22355 © 2015 Wiley Periodicals, Inc.
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Table 1. Baseline Clinical Characteristics of Patients According to BMI Classification
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
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
39 (7)
14 (12)
11 (6)
4 (4)
0.137
240 (59)
79 (59)
102 (60)
59 (56)
0.73
GFR (MDRD) (mL/min/1.73 m ), 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)
117 (29)
55 (42)
29 (17)
31 (31)
< 0.01
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
308 (75)
102 (77)
127 (76)
76 (74.5)
0.8
Variable
PVD, n (%) CAD, n (%) 2
P Value
III IV EuroSCORE, mean ± SD
Valve type (Corevalve), n (%)
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.
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).
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Clin. Cardiol. 38, 2, 76–81 (2015) M. Konigstein et al: Effect of BMI on TAVI outcomes Published online in Wiley Online Library (wileyonlinelibrary.com) DOI:10.1002/clc.22355 © 2015 Wiley Periodicals, Inc.
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 procedurerelated 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
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
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
Blood transfusions, n (%)
Abbreviations: BMI, body mass index.
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. 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.
heart disease in general and in patients undergoing PCI or cardiac surgery in particular.7 – 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-MilanoToulouse 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 procedurerelated 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 procedurerelated 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. Clin. Cardiol. 38, 2, 76–81 (2015) M. Konigstein et al: Effect of BMI on TAVI outcomes Published online in Wiley Online Library (wileyonlinelibrary.com) DOI:10.1002/clc.22355 © 2015 Wiley Periodicals, Inc.
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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 – 27 and also consistent with the recent analysis from the FRANCE2 (French Aortic National CoreValve and Edwards 2) registry,28 according to which, among the TAVI population, overweight and obesity were associated with improved 1year 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 – 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 nonprespecified 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.
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Conclusion In our single center study, obesity and overweight were independently associated with better outcome, supporting the obesity paradox in the TAVI population.
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Clin. Cardiol. 38, 2, 76–81 (2015) M. Konigstein et al: Effect of BMI on TAVI outcomes Published online in Wiley Online Library (wileyonlinelibrary.com) DOI:10.1002/clc.22355 © 2015 Wiley Periodicals, Inc.
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Address for correspondence: Maayan Konigstein, MD, Department of Cardiology, Affiliated to the Sackler School of Medicine, Tel Aviv University, Tel Aviv Medical Center, 6 Weitzman Street , Tel Aviv 64239, Israel [email protected]
Department of Cardiology, Tel-Aviv Medical Center, and the Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel
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 – 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 – 10 other studies showed no such protective effect, and even showed a detrimental effect of overweight patients compared with normal weight patients.11 – 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
The authors have no funding, financial relationships, or conflicts of interest to disclose.
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Clin. Cardiol. 38, 2, 76–81 (2015) Published online in Wiley Online Library (wileyonlinelibrary.com) DOI:10.1002/clc.22355 © 2015 Wiley Periodicals, Inc.
Considering the well-documented association between obesity and cardiovascular morbidity and mortality,16 – 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 Received: August 24, 2014 Accepted with revision: October 8, 2014
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 25 kg/m2 ), increased BMI was associated Clin. Cardiol. 38, 2, 76–81 (2015) M. Konigstein et al: Effect of BMI on TAVI outcomes Published online in Wiley Online Library (wileyonlinelibrary.com) DOI:10.1002/clc.22355 © 2015 Wiley Periodicals, Inc.
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Table 1. Baseline Clinical Characteristics of Patients According to BMI Classification
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
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
39 (7)
14 (12)
11 (6)
4 (4)
0.137
240 (59)
79 (59)
102 (60)
59 (56)
0.73
GFR (MDRD) (mL/min/1.73 m ), 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)
117 (29)
55 (42)
29 (17)
31 (31)
< 0.01
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
308 (75)
102 (77)
127 (76)
76 (74.5)
0.8
Variable
PVD, n (%) CAD, n (%) 2
P Value
III IV EuroSCORE, mean ± SD
Valve type (Corevalve), n (%)
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.
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).
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Clin. Cardiol. 38, 2, 76–81 (2015) M. Konigstein et al: Effect of BMI on TAVI outcomes Published online in Wiley Online Library (wileyonlinelibrary.com) DOI:10.1002/clc.22355 © 2015 Wiley Periodicals, Inc.
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 procedurerelated 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
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
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
Blood transfusions, n (%)
Abbreviations: BMI, body mass index.
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. 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.
heart disease in general and in patients undergoing PCI or cardiac surgery in particular.7 – 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-MilanoToulouse 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 procedurerelated 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 procedurerelated 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. Clin. Cardiol. 38, 2, 76–81 (2015) M. Konigstein et al: Effect of BMI on TAVI outcomes Published online in Wiley Online Library (wileyonlinelibrary.com) DOI:10.1002/clc.22355 © 2015 Wiley Periodicals, Inc.
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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 – 27 and also consistent with the recent analysis from the FRANCE2 (French Aortic National CoreValve and Edwards 2) registry,28 according to which, among the TAVI population, overweight and obesity were associated with improved 1year 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 – 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 nonprespecified 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.
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Conclusion In our single center study, obesity and overweight were independently associated with better outcome, supporting the obesity paradox in the TAVI population.
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