Introduction: The “obesity paradox” in elderly patients suffering from percutaneous coronary intervention (PCI) remains a source of controversy. The present meta-analysis focused on exploring the real existence of “obesity paradox” in these patients. Methods: As of November 2022, PubMed, Cochrane, and Embase databases were comprehensively searched to identify articles reporting all-cause mortality according to diverse body mass index (BMI) categories after PCI among the old cases developing coronary artery disease (CAD). Summary estimates of relative risks (RRs) were assigned to four BMI groups, including underweight, normal weight, overweight, and obesity groups. Results: There were altogether nine articles involving 25,798 cases selected for further analysis. Relative to normal weight group, overweight and obesity groups had decreased all-cause mortality (RR: 0.86, 95% CI: 0.77–0.95 for overweight group; RR: 0.57, 95% CI: 0.40–0.80 for obesity group), while underweight group had elevated all-cause mortality (RR: 1.52, 95% CI: 1.01–2.29). Conclusion: Our study revealed an “obesity paradox” relation of BMI with all-cause mortality in elderly cases receiving PCI. In comparison with normal weight group, overweight and obesity groups had decreased all-cause mortality, while underweight group had increased all-cause mortality.

As we all know, obesity has become an increasing public health issue across most developed countries, which seriously threatens human health [1]. In addition, obesity has been extensively suggested to be a risk factor related to multiple cardiovascular diseases, which may be associated with obesity accelerating atherosclerotic processes and increasing cardiovascular burden [2]. Evidence strongly suggests that the incidence of adverse cardiovascular events increases with obesity, including hypertension, heart failure, and coronary artery disease (CAD) [3, 4], and obesity is associated with higher mortality [5]. Body mass index (BMI) is a measured parameter usually adopted for assessing obesity, which can be identified by dividing weight (kilograms) by height in meters squared (kg/m2). BMI is inversely related to mortality in CAD, which referred to the so-called “obesity paradox” [6, 7]. As suggested in some original articles, obesity and overweight BMIs have a decreased or similar mortality risk compared with normal BMI [8, 9]. Also, two meta-analyses have confirmed not only this inverse association but also the J-shaped relation of BMI with mortality [10, 11]. Similarly, this phenomenon has also been observed in several studies focusing on patients undergoing coronary revascularization [6, 7, 12, 13]. Although similar findings are reported in numerous articles, they are not supported by all. Shahim et al. [14] conducted meta-analysis on six randomized trials of cases receiving ST-segment elevation myocardial infarction who received primary PCI. According to their results, BMI did not significantly affect 1-year mortality. Overall, it remains unknown about the real existence of “obesity paradox” among cases receiving coronary revascularization.

Then, does this specific “obesity paradox” also exist among old PCI cases? Although obesity’s clinical impact on patients undergoing PCI has been widely assessed, little research has been done among the elderly patients. To explore “obesity paradox” among old cases, this meta-analysis systemically estimated the relation of BMI with all-cause mortality among elderly cases who received PCI.

The current meta-analysis was performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [15].

Search Strategy

Electronic databases containing PubMed, Cochrane, and Embase were comprehensively searched from inception to November 2022 to identify eligible studies that reported all-cause mortality according to BMI of elderly patients using search strategy below: “BMI” OR “body mass index” AND “PCI” OR “percutaneous coronary intervention.” Additionally, reference lists from related articles were also examined manually for identifying possibly related studies. Only articles published in English language were enrolled.

Eligibility Criteria

Article inclusion criteria were as follows: (1) all elderly cases (≥65 years) undergoing PCI, (2) articles reporting case and death numbers for every BMI category or those with enough data for calculating the numbers. Article exclusion criteria were as follows: (1) conference abstracts, reviews, letters, animal studies, and editorials; (2) studies without enough information; and (3) studies without related participants or results. Participants were categorized in line with the BMI category released by the World Health Organization (WHO), including underweight (<18.5 or <20 kg/m2), normal weight (18.5–24.9 kg/m2), overweight (25–29.9 kg/m2), and obesity (30–34.9 kg/m2).

Study Screening and Data Collection

By adopting screening criteria above, two independent authors were responsible for study selection and data collection. First of all, title and abstract screening were conducted on all the obtained articles, while full-text reading was conducted for the rest of the articles to examine their eligibility. Data below were collected from qualified articles, including author, published year, country, case number, male proportion, follow-up period, age limit, BMI category, and outcome. Any disagreement was settled down by the opinion from another reviewer or the whole research team.

Quality Evaluation

Newcastle-Ottawa scale (NOS) was used for assessing study quality [16]. All articles were scored 0–9 points with regard to comparability, selection, and outcome, with those of ≥6 points being deemed as high-quality articles.

Statistical Analysis

Statistical analysis was performed with STATA version 16.0 (StataCrop, College Station, TX, USA). Relative risks (RRs) together with 95% confidence intervals (CIs) were calculated for each article with the random-effects model, which were adopted to be raw data for generating the unadjusted RRs. Inter-study heterogeneity was estimated based on I2 statistics, with ≤50%, 50–75%, and ≥75% indicating low, medium, and high heterogeneities, separately [17]. For testing how each single article affected the pooled findings, this work conducted sensitivity analysis through eliminating one article each time [18]. Begger’s test and funnel plots were adopted for assessing possible publication bias [19]. p < 0.05 (two-sided) stood for statistical significance.

Article Screening

Figure 1 displays flowchart of article identification. Briefly, altogether 1985 citations were initially screened in electronic databases including Embase, PubMed, and Cochrane. Afterward, 542 duplicates were removed. For those rest of the 1,443 articles, their titles and abstracts were examined; as a result, 1,302 articles were removed. For those rest articles, 141 were selected through full-text reading. At last, nine articles satisfying eligibility standards were enrolled in the present meta-analysis [20‒28].

Fig. 1.

The flowchart of literature identification.

Fig. 1.

The flowchart of literature identification.

Close modal

Article Features

Table 1 [20‒28] displays basic article features. Altogether, nine studies that enrolled 25,798 subjects were included, which were published during 2013–2022. The sample size ranged from 990 to 9,394, and patients were followed up for 233 days to 6 years. In addition, two articles included ≥80 elderly patients, and the remaining articles had smaller age cutoffs but were all >65 years. Articles of NOS score >7 points were deemed to be high quality. Quality assessments are shown in online supplementary Table 1 (for all online suppl. material, see https://doi.org/10.1159/000537744).

Table 1.

Characteristics of included studies

AuthorYearCountryPatients, nFollow-up timeAge limitMale, %BMI categories, kg/m2Outcome
Lazzeri et al. [202013 Italy 1,268 42.6 months ≥75 years old 73.2 <20.0, 20.0–24.9, 25.0–29.9, ≥30.0 All-cause mortality 
He et al. [212015 China 1,077 1 years ≥75 years old 66.8 ≤20.0, 20.0–24.9, 25.0–29.9, ≥30.0 All-cause mortality 
Goel et al. [222016 USA 9,394 4.2 years ≥65 years old 66.2 <20.0, 20.0–25.0, 25.0–30.0, >30.0 All-cause mortality 
Fukuoka et al. [232019 Japan 1,634 620 days ≥70 years old 78.6 <20.0, 20.0–24.9, ≥25.0 All-cause mortality 
Leistner et al. [242019 Germany 990 233 days ≥80 years old 55.4 ≤24.1, 24.1–27.2, ≥27.2 All-cause mortality 
De Luca et al. [252020 Italy 1,048 367 days >74 years old 60.2 <25.7, ≥25.7 All-cause mortality 
Kim et al. [262021 Korea 2,489 1 years ≥80 years old 54.6 <18.5, 18.5–23.0, 23.0–27.5, ≥27.5 All-cause mortality 
Kanic et al. [272022 Slovenia 6,496 6.0 years >75 years old 69.1 <25.0, 25.0–29.9, 30.0–34.9, 35.0–39.9, ≥40.0 All-cause mortality 
Wang et al. [282022 China 1,429 59 months >65 years old 83.1 <24.0, 24.0–28.0, ≥28.0 All-cause mortality 
AuthorYearCountryPatients, nFollow-up timeAge limitMale, %BMI categories, kg/m2Outcome
Lazzeri et al. [202013 Italy 1,268 42.6 months ≥75 years old 73.2 <20.0, 20.0–24.9, 25.0–29.9, ≥30.0 All-cause mortality 
He et al. [212015 China 1,077 1 years ≥75 years old 66.8 ≤20.0, 20.0–24.9, 25.0–29.9, ≥30.0 All-cause mortality 
Goel et al. [222016 USA 9,394 4.2 years ≥65 years old 66.2 <20.0, 20.0–25.0, 25.0–30.0, >30.0 All-cause mortality 
Fukuoka et al. [232019 Japan 1,634 620 days ≥70 years old 78.6 <20.0, 20.0–24.9, ≥25.0 All-cause mortality 
Leistner et al. [242019 Germany 990 233 days ≥80 years old 55.4 ≤24.1, 24.1–27.2, ≥27.2 All-cause mortality 
De Luca et al. [252020 Italy 1,048 367 days >74 years old 60.2 <25.7, ≥25.7 All-cause mortality 
Kim et al. [262021 Korea 2,489 1 years ≥80 years old 54.6 <18.5, 18.5–23.0, 23.0–27.5, ≥27.5 All-cause mortality 
Kanic et al. [272022 Slovenia 6,496 6.0 years >75 years old 69.1 <25.0, 25.0–29.9, 30.0–34.9, 35.0–39.9, ≥40.0 All-cause mortality 
Wang et al. [282022 China 1,429 59 months >65 years old 83.1 <24.0, 24.0–28.0, ≥28.0 All-cause mortality 

USA, United States; BMI, body mass index.

BMI and All-Cause Mortality

All those nine studies reported all-cause mortality for normal weight and overweight cases receiving PCI, and altogether five studies reported the estimates for underweight patients [20‒23, 26]. Relative to the normal weight group, the underweight group was associated with an increased all-cause mortality risk (RR: 1.52, 95% CI: 1.01–2.29) (Fig. 2), whereas overweight and obesity groups were associated with decreased RRs (0.86, 95% CI: 0.77–0.95) and (0.57, 95% CI: 0.40–0.80), separately (Fig. 3, 4). Heterogeneity analysis was significant among underweight (I2 = 59.4%, p = 0.043) and obese (I2 = 61.2%, p = 0.017) groups, but overweight group did not exhibit any obvious heterogeneity (I2 = 8.5%, p = 0.384). Sensitivity analysis was conducted through omitting one single article each time. Besides, the composite effect size remained unchanged by any article (Fig. 5-7). Funnel plots demonstrated a certain degree of asymmetry, which indicated the possible publication bias. Nonetheless, there was no publication bias assessed by Begger’s test (p = 0.462, 0.466, and 0.764 for underweight, overweight, and obesity, separately) (online suppl. Fig. 1).

Fig. 2.

RR of all-cause mortality with underweight group versus normal weight group.

Fig. 2.

RR of all-cause mortality with underweight group versus normal weight group.

Close modal
Fig. 3.

RR of all-cause mortality with overweight group versus normal weight group.

Fig. 3.

RR of all-cause mortality with overweight group versus normal weight group.

Close modal
Fig. 4.

RR of all-cause mortality with obese group versus normal weight group.

Fig. 4.

RR of all-cause mortality with obese group versus normal weight group.

Close modal
Fig. 5.

Sensitivity analysis of relative risks of all-cause mortality with underweight group versus normal weight group.

Fig. 5.

Sensitivity analysis of relative risks of all-cause mortality with underweight group versus normal weight group.

Close modal
Fig. 6.

Sensitivity analysis of relative risks of all-cause mortality with overweight group versus normal weight group.

Fig. 6.

Sensitivity analysis of relative risks of all-cause mortality with overweight group versus normal weight group.

Close modal
Fig. 7.

Sensitivity analysis of relative risks of all-cause mortality with obese group versus normal weight group.

Fig. 7.

Sensitivity analysis of relative risks of all-cause mortality with obese group versus normal weight group.

Close modal

Our results revealed that, relative to normal weight group, overweight and obesity groups showed decreased all-cause mortality, while underweight was associated with higher all-cause mortality, demonstrating an “obesity paradox” in elderly patients undergoing PCI. In CAD, J-shaped relation was detected in BMI category with mortality, meaning that underweight patients have the greatest mortality risk, whereas those of overweight and slight obesity have decreased mortality risk [29], which is called the “obesity paradox.” The “obesity paradox” is reported in additional disorders like heart failure, hypertension, diabetes, and peripheral artery disease [30‒33]. However, this phenomenon is rarely reported in elderly patients with CAD, and there are controversial outcomes from existing articles. As revealed by certain articles, “obesity paradox” does not exist in elderly patients with CAD. For example, He et al. [21] and Wang et al. [28] suggested no “obesity paradox” of BMI in cases aged ≥75 and >65 years. There are also contrary studies, based on the results of an original study showing the decreased mortality risk in elderly cases experiencing non-ST-segment elevation myocardial infarction who have overweight and obesity in comparison with those with normal weight, while underweight cases have significantly higher mortality [9]. Another study on ST-segment elevation myocardial infarction in the elderly patients also identifies that cases with mild-moderate obesity are associated with decreased mortality [34]. Although the above two studies partially demonstrate “obesity paradox” among elderly CAD cases, they examine cases receiving PCI and coronary artery bypass grafting together. Actually, patients receiving PCI and coronary artery bypass grafting are not similar enough for combined quantitative analysis. In the study of PCI patients only, Goel et al. [22] identified “obesity paradox” among the old cases receiving PCI and also verified the J-shaped relation of BMI category with mortality. Similarly, Fukuoka et al. [23] suggested the “obesity paradox” in elderly cases experiencing acute myocardial infarction who underwent PCI (≥70 years old). In the present work, just cases undergoing PCI were enrolled for analysis, and their findings were further corroborated. Although previous meta-analyses on CAD have fully elaborated relation of BMI category with mortality, none of them restricts age [10, 11, 29, 35‒37]. This is the first meta-analysis on BMI categories as well as all-cause mortality among the elderly patients undergoing PCI. The obtained results suggested the decreased all-cause mortality among cases with overweight and obesity relative to normal weight. In summary, this study suggested that “obesity paradox” existed among elderly cases receiving PCI.

Our study showed increased survival among elderly cases with overweight and obesity, and the phenomenon may be explained. For CAD cases, those with obesity have a low age compared with those with normal weight, in other words, obesity is associated with early CAD development [20, 38]. Due to early manifestation, obese cases are associated with a decreased CAD anatomy risk, thus improving prognosis following CAD revascularization procedures [39]. Nonetheless, this benefit will gradually attenuate as the severity of adiposity increases [7]. On the other hand, surgeons and physicians should make more efforts to perform aggressive coronary revascularization in obese cases [40]. Additionally, obese cases are more likely to receive the medication recommended by the guidelines and tolerate higher doses of cardioprotective drugs [41, 42]. Intensive medication can reduce adverse cardiovascular events and mortality rates. Noteworthily, the high mortality in underweight cases is associated with smoking [43], cachexia [44], and malnutrition [45], which may contribute to the relative benefits of overweight and obesity. More importantly, BMI is not effective on distinguishing lean body mass from body fat [10], and the increased lean body mass may be related to the superior cardiovascular disease prognostic outcome [46]. Cases with overweight and obesity are associated with superior prognostic outcome, probably because of the elevated lean body mass rather than increased body fat. All in all, the above confounders can partially account for “obesity paradox.”

Several limitations should be noted in this meta-analysis. First of all, some articles enrolled in the present work did not classify patients with standard WHO BMI category. Particularly, some studies classify normal weight and underweight individuals, or overweight and obese individuals together, which affected the result reliability. However, sensitivity analysis demonstrated that these studies had no significant impact on our pooled findings. Secondly, BMI has been frequently adopted to describe obesity but only roughly measures obesity. Central obesity parameters (e.g., waist-hip ratio, waist circumference) had superior effect than BMI on predicting mortality, but our study did not provide these parameters. Therefore, it was impossible to evaluate their relation with all-cause mortality. Thirdly, this study did not include cases experiencing severe obesity (BMI ≥35 kg/m2); as a result, relevant data were not available for assessing relationship of severe obesity with clinical results. Also, this work measured BMI during the procedure, but did not re-evaluate it in follow-up, so the potential impact of weight changes during follow-up on prognosis remained unknown. Fourthly, this study only included elderly patients undergoing PCI, which limited the generality of our findings. Fifthly, there are many prognostic indicators (e.g., MI and target vessel revascularization), however, just all-cause mortality was assessed in the present work. Thus, relations of additional prognostic factors with BMI need further investigations. Finally, our meta-analysis used unadjusted relative risk values, as a result, the confounding effects might potentially affect our results.

Our study shows an “obesity paradox” relationship of BMI with all-cause mortality among elderly cases undergoing PCI. However, few articles have explored “obesity paradox” in elderly patients, and its underlying mechanisms are not yet comprehensively understood. Therefore, more prospective studies in elderly patients with CAD are warranted in the future to confirm this association and further explore the underlying mechanism.

An ethics statement is not applicable because this study is based exclusively on published literature.

The authors have no conflicts of interest to declare.

The present study was financially supported by the Key Project of Health of Chongqing Science and Technology Bureau (No. CSTC2021jscx-gksb-N0016), the Kuanren Talent Program of the Second Affiliated Hospital of Chongqing Medical University (No. KRYC-GG-2113), the Project of Chongqing Sports Bureau (No. C202005), and the Chongqing Joint Scientific Research Project of Science and Technology (No. 2021MSXM094). All funders were not involved in designing the study, collecting or analyzing data, making decision on publication, and preparing this manuscript.

Yunhui Wang and Wei Deng designed the study. Yunhui Wang, Junwu Li, Yulian Zhang, and Wei Deng drafted the manuscript. Yunhui Wang, Shiyu Chen, and Fang Zheng prepared the table and figure. All authors participated in the revision of the manuscript and read and approved the final manuscript.

All data generated or analyzed during this study are included in this article. Further inquiries can be directed to the corresponding author.

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