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. 2026 Feb 23;21(2):e0343062. doi: 10.1371/journal.pone.0343062

Relative fat mass and cardiovascular risk in Peruvian adults: Findings from a national survey

José A Chaquila 1, Akram Hernández-Vásquez 2,*, Jamee Guerra Valencia 3, Fresia Miranda-Torvisco 1, Gianella Ramirez-Jeri 1
Editor: Neftali Eduardo Antonio-Villa4
PMCID: PMC12928448  PMID: 41729888

Abstract

Background

In the Region of the Americas, particularly in low- and middle-income countries such as Peru, cardiovascular disease (CVD) remains one of the leading causes of mortality. A positive association has also been described between body fat percentage and CVD risk.

Objective

To evaluate the association between obesity, defined by Relative Fat Mass (RFM, an anthropometric indicator that estimates total body fat), and 10-year cardiovascular risk estimated by the Framingham risk score.

Methods

A cross-sectional study was conducted using data from the Food and Nutrition Surveillance by Life Stages survey (2017–2018) in Peru. Obesity was the exposure variable defined by RFM. The RFM was also analyzed both as a continuous and categorical variable. Generalized linear models of the gamma family with a logarithmic link were applied and stratified by sex.

Results

Data from 651 adults were analyzed. The prevalence of obesity was 78.2% in women and 42.7% in men. After adjusting for age, poverty, fruit and vegetable consumption, and altitude of residence, obesity defined by RFM was associated with higher estimated Framingham risk scores in both sexes (Women: β: 0.48; 95% CI: 0.32–0.63; Men: β: 0.39; 95% CI: 0.23–0.56. Similar results were observed when RFM was analyzed as a continuous variable and in tertiles.

Conclusion

Obesity defined by RFM was positively associated with estimated 10-year cardiovascular risk in both sexes, with stronger association in women. These results suggest that RFM may serve as a useful tool for assessing estimated 10-year cardiovascular risk, with implications for the design of public health interventions in Peru.

Introduction

Cardiovascular diseases (CVDs) represent one of the main challenges for health systems worldwide due to their high morbidity, mortality, disability, and economic burden [1]. In 2019, CVDs accounted for approximately 18.6 million deaths globally [2], with nearly 80% of these occurring in low- and middle-income countries [3]. In Latin America, the total number of prevalent CVDs cases more than doubled between 1990 and 2021, rising from 20 million to 47 million during this period [1]. Although Peru is among the countries with the lowest cardiovascular mortality rates in the region [4], nearly one-third of its population met no more than two out of five markers of cardiovascular health [5].

Obesity is an independent risk factor for several comorbidities, including hypertension and dyslipidemia [6]. A direct relationship has been described between body fat percentage, particularly visceral fat, and CVDs risk [7,8]. Although reference techniques such as dual-energy X-ray absorptiometry (DEXA) can assess body adiposity, their high costs and infrastructure requirements limit their use in clinical and population-based settings [9]. For this reason, anthropometric indicators remain valuable in both clinical practice and population studies because they characterize body composition and are associated with health outcomes [10], while being inexpensive and easy to obtain. Among these, the Relative Fat Mass (RFM) has emerged as an alternative anthropometric marker for obesity diagnosis. RFM has been validated against DEXA and is calculated from sex, height, and waist circumference, providing a practical estimate of body fat percentage [11]. Moreover, its predictive discrimination for heart disease mortality (0.64 in women and 0.67 in men) has been shown to be higher than that of body mass index (BMI) (0.53 and 0.56) and waist circumference (0.60 and 0.64) [12]. In addition, compared to BMI and waist circumference (WC), RFM has demonstrated a greater predictive discrimination for heart disease mortality in both sexes. Likewise, the proportion of preventable heart disease mortality attributed to RFM-diagnosed obesity was higher than that observed when using BMI or WC [12]. These findings add to previous evidence that also supports the use of RFM as a useful tool for predicting cardiovascular risk [13].

Several tools are currently available to estimate CVDs risk in adults, with risk scores being particularly useful for stratification. Among them, the Framingham risk score [14] is one of the most widely used, allowing the estimation of 10- and 30-year cardiovascular risk based on lifestyle and clinical predictors [15]. It is also recommended by the Peruvian Ministry of Health for assessing 10-year cardiovascular risk [16]. Previous studies have reported associations between the Framingham risk score and anthropometric indicators of obesity [17], however these were conducted in populations with different ethnic backgrounds than Peru. Considering that differences in body composition and ethnicity modulate cardiovascular risk association [18], findings from high-income countries or predominantly Caucasian populations may not represent Latin American or Andean contexts. Given that CVD-related mortality in Peru increased by more than 70% between 2017 and 2022 [19], it is important to improve methods for predicting CVDs. To our knowledge, no study has evaluated the association between obesity defined by RFM and estimated 10-year cardiovascular risk using the Framingham score in a Peruvian population. Therefore, this study aimed to evaluate the association between obesity defined by RFM, considered under different operationalization approaches (binary, continuous, and tertile-based) and 10-year cardiovascular risk stratified by sex, as estimated by the Framingham risk score in Peruvian adults who participated in a national survey during 2017–2018. The present study advances knowledge beyond prior international RFM studies by comparing multiple operationalizations of RFM (binary, continuous, and tertiles) and applying sex-stratified analyses within a complex survey design in a nationally representative Latin American population, providing novel insights into optimal analytical strategies for RFM-estimated cardiovascular risk assessment in ethnically diverse contexts.

Materials and methods

Study type and design

An analytical cross-sectional study was conducted using the data from the 2017–2018 Food and Nutrition Surveillance by Life Stages (VIANEV) survey. The VIANEV survey has national representativeness and includes data collected on anthropometric measurements, lifestyle habits, and biochemical analyses of Peruvian adults aged 18–59 years, with a fasting period of at least 9–12 hours [20]. The survey excluded adults who consumed food prior to biochemical assessments, those with gastrointestinal diseases affecting diet, and those with anatomical conditions preventing accurate anthropometric measurement. Further methodological details of the survey are available in the official technical report [20].

The survey collected information across three domains: Metropolitan Lima (the capital of Peru), the rest of the urban area and rural areas, using a stratified, multistage, probabilistic, and independent sampling design. Sampling was conducted in two stages: first, by randomly selecting clusters as the primary sampling unit, and subsequently by randomly selecting households with adult members as the primary unit. The VIANEV 2017–2018 survey was conducted among a subsample of adults who also participated in the National Household Survey 2017 (ENAHO). ENAHO constitutes one of the largest population-based surveys in Peru and widely used to inform health decision-making and guide public policy in the country. In contrast to ENAHO, which focuses primarily on demographic and economic aspects, VIANEV participants were asked a broader set of health-related questions [21].

Study population

Adults aged 30–59 years were included in the present analysis. Participants younger than 30 years were excluded because the development and validation of the Framingham risk score and the estimation of 10-year cardiovascular risk were performed in adults aged 30–74 years [14]. Therefore, estimating 10-year cardiovascular risk in younger individuals would not reflect a real risk [22]. Additionally, participants with missing values in any of the variables of interest were excluded.

Variables

Exposure variable: obesity.

Obesity was defined using the RFM index, calculated from height (cm), WC (cm), and sex of participants. WC was measured using a 200-cm measuring tape with 1-mm precision, positioning it at the midpoint between the lower margin of the last rib and the upper border of the iliac crest. Height was assessed with a fixed wooden stadiometer [20]. The following calculation was performed [11]:

RFM: 64(20 × (height/waist circumference)) + (12 × sex)

where sex was coded as 0 for men and 1 for women. Cut-off points of ≥40% for women and ≥30% for men were applied to define obesity as a dichotomous variable (No/Yes). The selection of these cut-off points was based on prior validation studies for obesity diagnosis and mortality prediction [23], as well as their use in a Peruvian population-based survey [24].

Outcome variable: cardiovascular risk.

The 10-year cardiovascular risk was analyzed as a continuous variable and estimated using the Framingham risk score [14]. This score was proposed by D’Agostino et al. in 2008 using data from adults enrolled in the Framingham Heart Study. For the development of this score, eligible participants were those who attended examination cycles conducted between 1968 and 1987, had high-density lipoprotein cholesterol measurements available, and were free of CVDs at baseline. From the initial assessment, the incidence of cardiovascular events was monitored, and the risk factors that significantly predicted these events were evaluated to construct a points-based score for estimating 10-year cardiovascular risk. The score assigns risk points through an algorithm that incorporates previously identified factors: age (years), sex, systolic blood pressure, high-density lipoprotein cholesterol, total cholesterol, smoking status, diabetes diagnosis (defined as fasting glucose ≥126 mg/dL or use of diabetes-related medication), and use of antihypertensive medication. Higher scores indicate greater risk of cardiovascular events within 10 years [14]. The score was calculated using the framingham command in Stata SE version 18.

Covariates.

The following variables were considered as potential confounders: age (30–39, 40–49, and 50–59 years); educational attainment (up to primary, secondary, and higher) [25]; daily sedentary time (<7 hours and ≥8 hours) [26]; household poverty status (yes/no) based on household expenditure; daily consumption of five or more servings of fruits and vegetables (yes/no) [27]; alcohol consumption in the past 30 days (yes/no); household residence (urban/rural) and altitude residence (0–499, 500–2499, and ≥2500 meters above sea level (masl) [24]. The selection of these variables was based on epidemiological criteria.

Statistical analysis

All statistical analyses were performed using Stata version 18 (StataCorp LLC). To obtain additional socioeconomic information of VIANEV participants, the VIANEV 2017–2018 database was merged with the ENAHO 2017 survey using strata, clusters, dwellings, and households as linkage variables.

Given the characteristics of the VIANEV survey, the analyses accounted for sample weights and the complex survey design. All analyses were stratified by sex to account for sex-specific differences in body composition. Participant characteristics were described using absolute frequencies, weighted frequencies (with 95% confidence intervals [95% CI]), and measures of central tendency (means and medians) with their respective measures of dispersion (standard deviation and interquartile range).

To assess the association between RFM and the Framingham risk score, crude and adjusted generalized linear models (GLMs) from the gamma family with a logarithmic link function were employed. All covariates were included in the adjusted models based on their epidemiological relevance. This model was chosen because it is appropriate for positively skewed continuous outcomes such as Framingham score values. The strength of association was expressed as β coefficients with their 95% CI and standard errors. Additionally, as a sensitivity analysis, GLMs were also fitted considering RFM as a continuous variable and categorized into tertiles derived from our own sample, with the highest tertile representing the greatest RFM values.

Ethical considerations

The VIANEV 2017–2018 survey data are publicly available and do not contain information that allows identification of participants. The dataset was accessed for research purposes on April 29, 2025, through the Peruvian National Open Data Platform (https://datosabiertos.gob.pe/dataset/estado-nutricional-en-adultos-de-18-59-a%C3%B1os-per%C3%BA-2017-%E2%80%93-2018). Similarly, ENAHO data are publicly available at https://proyectos.inei.gob.pe/microdatos/. At no point did the authors have access to identifiable information about the participants. The interviewees provided their verbal consent to participate. Therefore, approval from an institutional ethics committee was not required.

Results

A total of 651 participants were included, of whom 58.2% were women. Among men, those under 39 years of age predominated, whereas among women, the majority were aged 40–49 years. In both sexes, higher education, sedentary behavior, and non-poor households were more prevalent. Regarding the daily consumption of five or more servings of fruits and vegetables, men reported a higher intake. In addition, most households were located in urban areas and at altitudes below 500 masl (Table 1).

Table 1. Sample characteristics by sex in adults aged 30–59 years, VIANEV Survey.

Characteristics Male Female
n % weighted n % weighted
Age group (years)
 30–39 96 36.9 (30.6-43.6) 135 34.6 (29.1-40.5)
 40–49 84 29.8 (24.2-36.0) 136 37.2 (31.6-43.3)
 50–59 92 33.4 (27.2-40.2) 108 28.2 (23.6-33.3)
Educational level
 Up to Primary 60 17.7 (13.2-23.4) 126 25.3 (20.8-30.3)
 Secondary 116 39.9 (32.9-47.4) 130 34.9 (29.3-40.8)
 Higher 96 42.4 (35.3-49.7) 123 39.9 (34.0-46.1)
Sitting time
 Up to 7 hours 220 78.6 (71.7-84.2) 338 87.6 (82.8-91.2)
 8 hours or more 52 21.4 (15.8-28.3) 41 12.4 (8.8-17.2)
Household in poverty
 No 223 83.7 (77.8-88.2) 315 84.9 (80.5-88.5)
 Yes 49 16.3 (11.8-22.2) 64 15.1 (11.5-19.5)
Fruit and vegetable intake (≥5 servings/day)
 No 191 68.4 (61.1-74.8) 287 73.4 (67.4-78.6)
 Yes 81 31.6 (25.2-38.9) 92 26.6 (21.4-32.6)
Alcohol consumption
 No 109 32.8 (27.1-39.1) 230 56.4 (50.2-62.5)
 Yes 163 67.2 (60.9-72.9) 149 43.6 (37.5-49.8)
Residence area
 Rural 110 24.6 (20.8-28.8) 119 17.5 (14.7-20.6)
 Urban 162 75.4 (71.2-79.2) 260 82.5 (79.4-85.3)
Altitude residence (masl)
 0–499 176 73.6 (67.7-78.7) 272 74.2 (68.4-79.3)
 500–2499 44 11.1 (7.9-15.2) 51 11.4 (7.9-16.0)
 2500 or higher 52 15.3 (10.9-21.1) 56 14.4 (10.3-19.8)

masl.: meters above sea level.

All estimates accounted for the VIANEV sample design.

The prevalence of obesity was higher in women than in men, whereas the median estimated 10-year cardiovascular risk in men was more than three times higher than that observed in women (Table 2). In both sexes, a higher prevalence of obesity and higher estimated Framingham risk scores were observed with increasing age. Among men, obesity prevalence and Framingham risk scores were higher in those with greater educational attainment, whereas among women obesity prevalence was lower in those with higher education. In men, obesity prevalence and mean Framingham risk scores decline with increasing altitude, while no consistent pattern is observed among women. Additionally, when comparing the Framingham risk score between non-obese and obese participants, non-obese men (7.65) had a lower mean Framingham risk score than obese men (13.75) (mean difference: –6.11, 95% CI: –8.63 to –3.58, p < 0.001). Similarly, non-obese women (2.07) had a lower Framingham risk score than obese women (4.01) (mean difference: –1.95, 95% CI: –2.63 to –1.27, p < 0.001).

Table 2. Relative Fat Mass and the estimated 10-year Framingham Risk Score by sex and sociodemographic and lifestyle characteristics in Peruvian adults aged 30–59 years, VIANEV Survey.

Male Female
Characteristics Relative Fat Mass Framingham risk score Relative Fat Mass Framingham risk score
Mean High Mean Median Mean High Mean Median
SD % SD (p25, p75) SD % SD (p25, p75)
Overall 29.3 (4.2) 42.7 10.3 (9.1) 7.5 (3.9-13.4) 43.2 (3.9) 78.2 3.6 (3.9) 2.2 (1.3-4.1)
Age group (years)
 30–39 28.2 (3.8) 31.8 4.8 (3.9) 3.6 (2.4-5.6) 42.3 (4.7) 69.7 1.3 (0.9) 1.1 (0.7-1.6)
 40–49 29.7 (4.8) 43.1 8.6 (5.9) 7.3 (4.5-10.3) 43.5 (3.8) 81.6 3.1 (2.9) 2.4 (1.8-3.3)
 50–59 30.3 (3.7) 54.4 17.7 (10.1) 14.9 (10.2-22.4) 43.9 (3.5) 84.1 7.0 (5.1) 5.4 (3.5-9.2)
Educational level
 Up to Primary 26.9 (4.4) 16.6 9.3 (7.1) 8.5 (3.9-11.5) 44.4 (3.9) 89.8 3.9 (4.7) 3.0 (1.7-4.3)
 Secondary 29.2 (4.3) 40.6 9.9 (9.7) 6.6 (3.1-13.1) 43.6 (4.1) 82.1 3.3 (3.6) 2.0 (1.2-3.9)
 Higher 30.5 (3.4) 55.6 11.0 (8.6) 8.0 (4.9-13.4) 42.1 (3.5) 67.3 3.6 (3.8) 2.1 (1.3-4.2)
Sitting time
 Up to 7 29.1 (4.1) 41.4 10.4 (9.6) 7.3 (3.8-13.0) 43.3 (4.0) 79.7 3.5 (3.9) 2.4 (1.3-4.1)
 8 or more 30.2 (4.4) 47.6 9.8 (6.2) 8.0 (4.6-14.3) 42.1 (3.9) 67.4 3.9 (4.5) 1.8 (1.3-3.8)
Household in poverty
 No 29.8 (3.9) 45.7 10.8 (9.1) 7.9 (4.0-14.7) 43.1 (4.0) 76.6 3.7 (4.1) 2.2 (1.3-4.1)
 Yes 27.1 (4.7) 27.4 7.2 (7.1) 6.1 (2.8-8.6) 43.7 (3.9) 87.2 3.0 (2.8) 2.2 (1.1-3.9)
Fruit and vegetable intake
 No 29.5 (4.2) 45.9 10.1 (8.6) 7.4 (3.9-12.9) 43.1 (4.1) 77.6 3.7 (4.3) 2.4 (1.3-4.1)
 Yes 29.0 (3.9) 35.8 10.7 (9.5) 7.6 (3.6-14.0) 43.3 (3.5) 79.7 3.2 (3.0) 2.1 (1.2-3.9)
Alcohol consumption
 No 29.0 (4.7) 41.9 10.7 (8.9) 8.5 (4.5-13.1) 43.5 (3.7) 83.0 3.4 (3.6) 2.1 (1.4-4.1)
 Yes 29.5 (3.9) 43.1 10.1 (8.8) 6.8 (3.6-13.7) 42.7 (4.1) 71.9 3.8 (4.3) 2.4 (1.2-3.9)
Residence area
 Rural 27.3 (4.8) 25.8 7.8 (8.1) 6.0 (3.4-10.0) 43.2 (4.9) 83 3.4 (5.2) 2.5
(1.3-3.8)
 Urban 30.0 (3.6) 48.2 11.1 (8.5) 8.0 (4.0-14.7) 43.2 (3.7) 77.2 3.6 (3.6) 2.2 (1.3-4.3)
Altitude residence (masl)
 0–499 30.0 (3.7) 46.8 10.8 (8.6) 7.9 (4.0-14.7) 43.1 (4.1) 76.6 3.8 (4.2) 2.2 (1.3-4.5)
 500–2499 27.0 (5.4) 21.1 10.0 (12.9) 6.5 (3.3-12.6) 43.8 (3.2) 88.4 2.7 (2.2) 2.2 (1.1-3.9)
 2500 or higher 27.9 (4.3) 38.4 7.7 (5.8) 6.8 (4.6-8.9) 43.0 (3.8) 78.5 3.4 (3.2) 2.4 (1.4-3.9)

All estimates accounted for the VIANEV sample design. p25: 25th percentile, p75: 75th percentile, SD: standard deviation, masl: meters above sea level.

The association between obesity defined by RFM and the estimated 10-year Framingham risk score was positive in both the crude and adjusted models for both sexes. Regarding obesity, the adjusted models showed a higher coefficient in women. Additionally, to assess whether RFM retained the direction and significance of its association when analyzed as a continuous variable with the Framingham risk score, a sensitivity analysis was conducted, showing a similar positive coefficient in both sexes (Table 3).

Table 3. Associations between Relative Fat Mass and the estimated 10-year Framingham Risk Score by sex, VIANEV Survey.

Generalized linear model (GLM) of the gamma family
Crude Adjusted*
Model β (95% CI) SE β (95% CI) SE
Male
 Obesity by Relative Fat Mass
  No Reference Reference
  Yes 0.59 (0.37-0.81) 0.11 0.39 (0.23-0.56) 0.08
Female
 Obesity by Relative Fat Mass
  No Reference Reference
  Yes 0.66 (0.42-0.91) 0.12 0.48 (0.32-0.63) 0.08
Male
 Tertiles by Relative Fat Mass
  Low Reference Reference
  Medium 0.57 (0.30-0.84) 0.14 0.39 (0.19-0.59) 0.10
  High 0.83 (0.56-1.09) 0.13 0.61 (0.42-0.80) 0.10
Female
 Tertiles by Relative Fat Mass
  Low Reference Reference
  Medium 0.32 (0.05-0.60) 0.14 0.19 (0.03-0.35) 0.08
  High 0.68 (0.41-0.95) 0.14 0.47 (0.28-0.67) 0.10
Male
 Relative Fat Mass 0.10 (0.07-0.12) 0.01 0.07 (0.05-0.09) 0.01
Female
 Relative Fat Mass 0.06 (0.03-0.08) 0.01 0.06 (0.04-0.08) 0.01

SE: standard error, CI: confidence intervals, β: coefficient. All estimates accounted for the VIANEV sample design. * Adjusted for age group, area of residence, educational level, sitting time, poverty status, fruit and vegetable intake, alcohol consumption and altitude of residence.

Discussion

The objective of the present study was to evaluate the association between obesity defined by RFM and the estimated 10-year cardiovascular risk according to the Framingham risk score in Peruvian adults aged 30–59 years. A positive and significant association was observed in both sexes. Furthermore, it was found that for each unit increase in RFM, the estimated 10-year cardiovascular risk increased by 0.07 in men and 0.06 in women on the logarithmic scale, corresponding to approximately 7% and 6% higher estimated risk, respectively. This indicates that higher estimated total body fat percentage was associated with proportionally higher estimated 10-year cardiovascular risk. To the best of our knowledge, this is the first study to evaluate the association between RFM, an alternative estimator of total body fat percentage, and the estimated 10-year cardiovascular risk using the Framingham score.

Comparison with previous studies

The findings of this study revealed that the presence of obesity defined by RFM was associated with a 48% and 61% higher estimated 10-year cardiovascular risk in men and women, respectively, compared with non-obese individuals. Additionally, when stratifying by RFM tertiles, a dose-response relationship was observed, with the estimated 10-year cardiovascular risk in the highest tertile being 84% in men and 60% in women, compared with the lowest tertile. These results are consistent with previous evidence supporting the clinical utility of RFM in assessing cardiovascular risk, both in cross-sectional and prospective studies. For instance, in a cross-sectional analysis of more than 11,000 Chinese adults, each standard deviation increase in RFM was associated with higher odds of CVDs in men (OR: 1.66; 95% CI: 1.36–2.02) and women (OR: 1.26; 95% CI: 1.08–1.47) [28]. Similarly, in U.S. adults, RFM was significantly associated with CVDs in both sexes, with 4% higher odds in men and 3% higher odds in women when comparing the highest versus the lowest quintile of RFM [29]. Moreover, prospective studies have documented that higher RFM is associated with greater incidence of heart failure [30], as well as cardiovascular mortality [12]. Despite variability in the magnitude of the association between RFM and CVDs across studies, which may be attributed to differences in how outcomes are measured and defined, taken together, these findings support the potential clinical utility of RFM in cardiovascular risk assessment.

Potential explanatory mechanisms

The observed association between RFM and estimated CVDs risk may reflect both pathophysiological and methodological factors. RFM incorporates height and WC in estimating body fat percentage [11]. Waist circumference is a marker of central adiposity distribution, particularly visceral adiposity [31], which has been widely associated with cardiovascular risk factors [32]. Visceral adipose tissue is metabolically active and characterized by a more lipolytic and inflammatory profile than subcutaneous adiposity, and is associated with lipid and glucose metabolism disturbances [33]. Greater visceral adiposity has also been associated with higher blood pressure [34]. Consistent with this mechanistic framework, a longitudinal study in Peruvian adults reported that RFM-defined obesity was associated with a higher incidence of hypertension over five years, which represents a major component of cardiovascular risk, thereby supporting the relevance of RFM in cardiometabolic risk assessment [35]. Taken together, increased central adiposity has been closely related to several components of cardiovascular risk [14]. Consistent with this, it has been documented that for every 10 cm increase in WC, CVDs risk increases by 3.4% in women and 4% in men [36]. From a methodological perspective, RFM has been validated against DEXA, the gold standard for assessing body composition [9]. Furthermore, RFM is based on the height-to-waist ratio, essentially the inverse of the WHtR, which has shown a strong association with CVDs risk [36]. However, our results should be interpreted with caution as the Framingham risk score has neither been validated nor recalibrated for the Peruvian population. Chile is one of the few countries in the region that has undertaken efforts to recalibrate the model for its own population [37]. Since the score was originally developed using baseline cardiovascular event rates from a U.S. cohort, the absolute levels of predicted 10-year risk may differ substantially from those in the Peruvian context and other Andean countries. Nevertheless, the model likely preserves the relative ranking of individuals according to higher or lower estimated cardiovascular risk.

Sex-based differences

Additionally, our findings show a stronger association between obesity and estimated cardiovascular risk in women, which is consistent with evidence indicating a higher burden of cardiovascular risk factors in women compared to men [38]. In Peru, studies have consistently reported a higher prevalence of obesity and metabolic syndrome among women, who also have markedly higher odds of abdominal obesity, reinforcing sex-specific vulnerability in adiposity-related cardiometabolic risk [39,40]. Together, these findings may help contextualize why increases in RFM are associated with larger relative changes in estimated 10-year cardiovascular risk among women in our study.

On the other hand, epidemiological studies in Latin America [4] have reported a higher incidence of CVDs in men than in women (655 vs. 531 per 100,000 individuals), and additional evidence indicates that Peruvian men present worse cardiovascular health than women [5,41]. Of note, compared with previous reports, our results address related but not identical dimensions of cardiovascular risk. Evidence from other Andean populations shows that despite women having a higher prevalence of risk factors, men experienced higher cardiovascular event incidence, suggesting that estimated risk may not fully reflect observed outcomes [42]. This pattern suggests that a greater burden of risk factors does not necessarily translate into higher event incidence, and that sex-specific patterns of estimated cardiovascular risk may not align perfectly with observed outcomes. These findings do not contradict our results, as the Framingham Risk Score estimates predicted cardiovascular risk based on multiple factors, which may vary independently of actual event incidence. While our study assessed estimated 10-year risk, previous studies examined observed cardiovascular events. Both approaches are complementary and highlight the need for longitudinal studies in Peru to determine whether adiposity has differential cardiometabolic effects by sex and how these translate into actual outcomes.

Implications for public health and clinical practice

In the Region of the Americas, particularly in low- and middle-income countries such as Peru, CVDs remain one of the leading causes of mortality. In response, and within the framework of the Global Action Plan for the Prevention and Control of Noncommunicable Diseases [43], the World Health Organization has promoted the Global HEARTS Initiative [44], and its regional adaptation, HEARTS in the Americas, which aims to strengthen health service performance for CVDs prevention and control. A main component of this strategy is the estimation of 10-year cardiovascular risk and the use of simple, accessible tools for its calculation in resource-limited settings [45]. Given that the use of simple anthropometric indicators is key in these strategies, it is relevant to evaluate their relationship with cardiovascular risk estimates in local populations. In this context, our findings suggest that obesity defined by RFM is associated with higher 10-year cardiovascular risk, as estimated by the Framingham risk score, which may be useful for future research exploring the potential role of RFM as an anthropometric marker in cardiovascular risk stratification. Although BMI is widely used to define obesity and is also associated with CVDs [46], it has important limitations that may lead to misclassification when detecting adults with excess body fat [47]. A high BMI does not necessarily reflect greater adiposity, as it is derived from total body weight and does not differentiate by sex [48]. These findings seek to contribute to the growing body of evidence supporting the need to implement alternative diagnostic criteria for obesity that can more accurately estimate cardiometabolic risk in Peru. To advance this effort, several key steps are required. First, drawing on the experience of countries such as the United States [49] and the United Kingdom [50]—where WC and WHtR measurements are endorsed by clinical guidelines for estimated cardiovascular risk assessment—there is a need to recalibrate RFM for the Peruvian context, given the country’s distinct ethnic characteristics. This requires population-based studies that include a valid reference standard for adiposity, such as DEXA, as well as cardiometabolic outcomes that can inform the establishment of appropriate cut-off points. Subsequently, considering the simplicity and very low cost of measuring WC and height in primary care settings, implementing RFM through pilot studies would help quantify the cardiovascular risk that BMI commonly underestimates. The main barriers to implementation would likely include the need to update clinical guidelines and potential resistance among clinical personnel when adopting a new adiposity estimator.

Study limitations

This study has several limitations that should be considered when interpreting our findings. The analysis was based on secondary data from the VIANEV 2017–2018 survey; therefore, recording errors or missing information cannot be ruled out, as the data were collected for purposes other than this research. In addition, due to the cross-sectional design of the study, it is not possible to establish causality between exposure and outcome. Nevertheless, these results may represent an initial step toward the development of more complex methodologies aimed at identifying potential causal pathways between variables. Moreover, the characteristics of excluded participants may have influenced the strength of the reported associations. We also conducted a sensitivity analysis to evaluate whether the association retained its direction and significance when modifying the nature of the exposure variable (RFM). Furthermore, the measurement of anthropometric variables, although standardized, may vary across interviewers or equipment. Some self-reported variables, such as lifestyle habits or living conditions, may have been influenced by social desirability or recall bias. The lack of potentially confounding variables, such as diet quality, energy intake or more specific physical activity measurement, could also result in residual confounding, affecting the magnitude and direction of the estimated associations due to its strong influence on body fat percentage and components of the Framingham Risk Score; nevertheless, the adjustment models included indirect measures of diet quality (daily consumption of five or more portions of fruits and vegetables) and physical activity (daily hours of sedentary behavior) in order to reduce confounding, although residual confounding cannot be completely excluded. Although the Framingham risk score is widely used to estimate 10-year cardiovascular risk, its accuracy when applied outside the original U.S. population may lead to over- or underestimation of risk. In addition, the lack of validation in the Peruvian population may limit its applicability in this context. Nevertheless, the score is currently recommended by the Peruvian Ministry of Health for cardiovascular risk stratification [16], which supports its use in local epidemiological analyses. Finally, since the data were collected before the COVID-19 pandemic, patterns of obesity and cardiovascular risk may have shifted thereafter, restricting the direct applicability of our findings to the current context.

Conclusion

RFM was positively associated with the estimated 10-year Framingham risk score in Peruvian adults of both sexes, with a stronger association observed in women than in men. We recommend that future studies evaluate the interchangeability of RFM with commonly used anthropometric markers for estimating cardiovascular risk, in order to identify the simplest and most effective indicator for estimated cardiovascular risk assessment in the Peruvian population.

Acknowledgments

We express our gratitude to the National Institute of Statistics and Informatics of Peru and the National Center for Food and Nutrition of Peru for conducting the data collection and for making these data publicly available, thereby enabling research that contributes to the improvement of public health policies in the country.

Data Availability

The dataset is accessible through the Peruvian National Open Data Platform (https://www.datosabiertos.gob.pe/dataset/estado-nutricional-en-adultos-de-18-59-a%C3%B1os-per%C3%BA-2017-%E2%80%93-2018). Similarly, ENAHO data are publicly available at https://proyectos.inei.gob.pe/microdatos/.

Funding Statement

The author(s) received no specific funding for this work.

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Decision Letter 0

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12 Nov 2025

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

Reviewer #1: Yes

Reviewer #2: Partly

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2. Has the statistical analysis been performed appropriately and rigorously? -->?>

Reviewer #1: I Don't Know

Reviewer #2: No

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Reviewer #2: Yes

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Reviewer #1: The manuscript addresses an important public health question: the association between relative fat mass (RFM) and 10-year cardiovascular risk in a Peruvian population. The topic is timely, especially given the high burden of obesity and CVD in low- and middle-income countries. The paper is well-organized, methodologically sound, and provides valuable findings. However, several aspects require clarification and strengthening before the manuscript can be considered for publication.

1.Novelty and Contribution

- The authors state this is the first study in Peru to link RFM with the Framingham risk score. While this is true, the novelty should be emphasized more clearly in the Introduction and Discussion. At present, the contribution is somewhat underplayed against the backdrop of existing international studies.

2. Choice of Cardiovascular Risk Tool

- The Framingham risk score has not been validated in the Peruvian population, as the authors themselves note. This limitation is significant and may affect the accuracy of the estimates. The Discussion should more critically evaluate the implications of using this score and consider whether recalibrated regional risk equations (if available) might yield different results.

3. Cross-Sectional Design

- The limitation that causality cannot be inferred should be highlighted earlier (e.g., in the Abstract or Introduction), not only in the Discussion. The authors should also consider whether reverse causality (e.g., CVD risk factors influencing body fat distribution) could bias results.

4. Definition of Obesity via RFM

- The rationale for the chosen cut-off points (≥40% for women and ≥30% for men) is based on international validation studies. However, whether these cutoffs are appropriate for the Peruvian population is uncertain. Could the authors provide sensitivity analyses using alternative thresholds or justify more strongly why these cutoffs are optimal locally?

5. Statistical Methods

-The use of generalized linear models of the gamma family with a log link is appropriate for skewed outcomes. However, the paper would benefit from an explanation of why this model was selected over alternatives (e.g., quantile regression). Additionally, please clarify whether survey weights and clustering were fully accounted for in all regression analyses.

6. Potential Confounders

-Important confounders such as alcohol consumption, physical activity beyond sedentary time, and dietary quality were not included. The absence of these variables should be acknowledged as a limitation in more detail.

7. Sex-Specific Findings

- The stronger association in women is intriguing. The Discussion offers some explanations (biological and social), but these remain speculative. The authors should expand on possible mechanisms and highlight the need for future longitudinal research to clarify causality.

8. Abstract

- The Abstract is concise, but the phrase “positively associated” could be replaced with a more precise quantitative description (e.g., “associated with a 61% higher predicted risk in women”).

9. Line 63–69: The claim that RFM’s discriminatory capacity surpasses BMI and waist circumference should be better referenced, and the cited evidence summarized more explicitly.

10. Methods

- Please specify how missing data were handled (listwise deletion vs. imputation).

- Clarify whether waist circumference was measured at the midpoint between the lowest rib and iliac crest or at another anatomical site.

11. Results

- Tables are informative but could be more reader-friendly if prevalence ratios (PRs) were included directly in Table 3 rather than only in the footnotes.

- Consider reporting absolute mean differences in Framingham scores between obese and non-obese participants for interpretability.

12. Discussion

- The section on public health implications (lines 263–280) could be expanded to comment on how RFM might realistically be integrated into Peruvian clinical practice and whether it could replace or complement BMI in national guidelines.

- Please update references to regional guidelines or ongoing WHO/PAHO initiatives to strengthen applicability.

Reviewer #2: well structured manuscipt. although, stduy have not add a new to knowledge as the topic is previousely known, the following suggestions may improve it more :

Methodology: because you retrieve a seconday data so its preferde to refered as Retreospective SURVEY correation design)

* explain the sampling processes in you maunscript (*how you select the participants within your study) as what discussed here is about the population and inclusion criteria of primary survey!

* most important is regaerding the Framingham risk score : WHEN AND HOW THE STUDY WAS APPLIED THE SCORE ? ; the scoring system must be also eplained

confusion was arised between the VIANEV and ENAHP ?? explain!

statistical analysis: median is not required as the RFM is a continous variable (Mean is enough)

correlation coefficient is required to investigate the correlation

Results : MASL abberivation (NO space )

TABLE 2; you have to include the correlation coefficient (r) and sig so the table must provide a valuable data

table 3 ; full detailed regression ,odel must be provided so the study can predicte or exclude the cofounding factors

duiscussion: well, its preffered to also add discussion about the table 2 (after you made the mentioned comments regarding the tabel 2)

conclusion: must include the main finding of table 2

**********

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Reviewer #1: No

Reviewer #2: No

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PLoS One. 2026 Feb 23;21(2):e0343062. doi: 10.1371/journal.pone.0343062.r002

Author response to Decision Letter 1


9 Dec 2025

RESPONSE LETTER

Authors’ comments: We thank both reviewers for their comments. With their input and the changes made, we believe that the manuscript has improved substantially.

Reviewer #1:

The manuscript addresses an important public health question: the association between relative fat mass (RFM) and 10-year cardiovascular risk in a Peruvian population. The topic is timely, especially given the high burden of obesity and CVD in low- and middle-income countries. The paper is well-organized, methodologically sound, and provides valuable findings. However, several aspects require clarification and strengthening before the manuscript can be considered for publication.

1.Novelty and Contribution

- The authors state this is the first study in Peru to link RFM with the Framingham risk score. While this is true, the novelty should be emphasized more clearly in the Introduction and Discussion. At present, the contribution is somewhat underplayed against the backdrop of existing international studies.

Response: Thank you for the suggestion. We have added a text in the introduction acknowledging that differences in body composition and ethnicity modulate the association with cardiovascular risk

Changes: A text was added to the introduction section. Now it reads:

“Considering that differences in body composition and ethnicity modulate cardiovascular risk association [18], findings from high-income countries or predominantly Caucasian populations may not represent Latin American or Andean contexts.”

2. Choice of Cardiovascular Risk Tool

- The Framingham risk score has not been validated in the Peruvian population, as the authors themselves note. This limitation is significant and may affect the accuracy of the estimates. The Discussion should more critically evaluate the implications of using this score and consider whether recalibrated regional risk equations (if available) might yield different results.

Response: Thank you for the observation. We agree that lack of validation of the Framingham risk score in the Peruvian population may affect the accuracy of the estimates. This limitation was acknowledged in the Discussion section, where we state: “Although the Framingham score is widely used to estimate 10-year cardiovascular risk, its accuracy when applied outside the original U.S. population may lead to over- or underestimation of risk. In addition, the lack of validation in the Peruvian population may limit its applicability in this context.”

It is important to note that the Framingham risk score is endorsed by the Peruvian Ministry of Health as a reference tool for cardiovascular risk stratification, which supports its use in local clinical and epidemiological settings. We have incorporated an additional sentence acknowledging this.

Additionally, we have incorporated a text in the discussion section regarding the implications of this lack of validity in interpreting our findings

Changes: In the discussion section we added the following text:

“However, our results should be interpreted with caution as the Framingham risk score has neither been validated nor recalibrated for the Peruvian population. Chile is one of the few countries in the region that has undertaken efforts to recalibrate the model for its own population [37]. Since the score was originally developed using baseline cardiovascular event rates from a U.S. cohort, the absolute levels of predicted 10-year risk may differ substantially from those in the Peruvian context and other Andean countries. Nevertheless, the model likely preserves the relative ranking of individuals indicating who presents higher or lower estimated cardiovascular risk.”

We have added the following text to the limitations section:

“Nevertheless, the score is currently recommended by the Peruvian Ministry of Health for cardiovascular risk stratification [16], which supports its use in local epidemiological analyses”

3. Cross-Sectional Design

- The limitation that causality cannot be inferred should be highlighted earlier (e.g., in the Abstract or Introduction), not only in the Discussion. The authors should also consider whether reverse causality (e.g., CVD risk factors influencing body fat distribution) could bias results.

Response: Thank you for this observation. According to the STROBE report guidelines (https://pmc.ncbi.nlm.nih.gov/articles/PMC2034723/), the study limitations should be reported in the Discussion section. They recommend summarizing what was done and found in the Abstract, while the Introduction should present the state of the art regarding the problem and outline the objectives. In the Discussion section, the limitations of the study should indeed be addressed, as specified in the guideline. Therefore, in order to follow established reporting standards, we have kept the limitations in the Discussion section.

Regarding the possibility of reverse causality, we consider it unlikely in this context. The Framingham Risk Score represents an estimate of future cardiovascular risk rather than past or current clinical event. Thus, it cannot temporally precede or influence current body composition. For this reason, due to the nature of the Framingham Risk Score, reverse causality with the RFM—which does estimate current body fat percentage—is very unlikely. Additionally, we consider that having already stated in the abstract that our study will assess an association is sufficient for the reader’s understanding.

Changes: None

4. Definition of Obesity via RFM

- The rationale for the chosen cut-off points (≥40% for women and ≥30% for men) is based on international validation studies. However, whether these cutoffs are appropriate for the Peruvian population is uncertain. Could the authors provide sensitivity analyses using alternative thresholds or justify more strongly why these cutoffs are optimal locally?

Response: Thank you for the observation. We agree on the importance of the cut-off selection for defining obesity using the RFM. Nevertheless, as ethnic and anthropometric diversity across countries can influence body composition, cut-off points developed in other populations may not be appropriate for the Peruvian context. In line with this, the Lancet Commission on clinical obesity recommends using country-specific cut-off points when determining an obesity diagnosis (1). However, given the absence of validated RFM cut-off points for the Peruvian population and the variability of those proposed in different countries (Table A), we decided to use the original study’s cut-offs (≥40% for women and ≥30% for men). It is important to note that to address concerns regarding threshold dependence, we also conducted a sensitivity analysis treating RFM as a continuous variable, without applying a specific cut-off.

1. Rubino F, Cummings DE, Eckel RH, et al. Definition and diagnostic criteria of clinical obesity. Lancet Diabetes Endocrinol. 2025;13(3):221-262. doi:10.1016/S2213-8587(24)00316-4

Table A. Cutoff points for defining obesity according to RFM used in different countries.

Study Population study Cut-off-point

Usefulness of relative fat mass in estimating body adiposity in Korean adult population

https://www.jstage.jst.go.jp/article/endocrj/66/8/66_EJ19-0064/_article/-char/ja/

Corea ≥25 men

≥35 women

Relative fat mass and prediction of incident atrial fibrillation, heart failure and coronary artery disease in the general population

https://www.nature.com/articles/s41366-023-01380-8

Netherlands ≥26 men

≥38 women

Predictive values of relative fat mass and body mass index on cardiovascular health in community-dwelling older adults: Results from the Longevity Check-up (Lookup) 7+

https://www.maturitas.org/article/S0378-5122(24)00106-3/fulltext

Italy ≥27 men

≥40 women

Relative fat mass as an estimator of body fat percentage in Chilean adults

https://www.nature.com/articles/s41430-024-01464-2

Chile ≥22,7 men

≥32,4 women

In addition, and in response to the reviewer’s concern, we conducted an additional sensitivity analysis using a statistical criterion based on tertiles and is reported in the New Table 3. The results showed the same pattern as those obtained with the original cut-offs.

Changes: We conducted an additional sensitivity analysis using a tertile-based classification derived from our own sample. The results of this analysis have been incorporated into the revised manuscript and added to Table 3.

Table 3. Associations between Relative Fat Mass and the 10-year Framingham Risk Score by sex

Generalized linear model (GLM) of the gamma family

Crude Adjusted*

Model β (95% CIs) SE β (95% CIs) SE

Male

Obesity by Relative Fat Mass

No Reference Reference

Yes 0.59 (0.37-0.81)a 0.11 0.39 (0.23-0.56)b 0.08

Female

Obesity by Relative Fat Mass

No Reference Reference

Yes 0.66 (0.42-0.91)c 0.12 0.478 (0.32-0.63)d 0.08

Male

Tertiles by Relative Fat Mass

Low Reference Reference

Medium 0.57 (0.30-0.84) 0.14 0.39 (0.19-0.59) 0.10

High 0.83 (0.56-1.09) 0.13 0.61 (0.42-0.80) 0.10

Female

Tertiles by Relative Fat Mass

Low Reference Reference

Medium 0.32 (0.05-0.60) 0.14 0.19 (0.03-0.35) 0.08

High 0.68 (0.41-0.95) 0.14 0.47 (0.28-0.67) 0.10

Male

Relative Fat Mass 0.10 (0.07-0.12) 0.01 0.07 (0.05-0.09) 0.01

Female

Relative Fat Mass 0.06 (0.03-0.08) 0.01 0.06 (0.04-0.08) 0.01

SE: standard error, CIs: confidence intervals, β: coefficient. All estimates accounted for the VIANEV sample design. * Adjusted for age group, area of residence, educational level, sitting time, poverty status, fruit and vegetable intake, alcohol consumption and altitude of residence.

5. Statistical Methods

-The use of generalized linear models of the gamma family with a log link is appropriate for skewed outcomes. However, the paper would benefit from an explanation of why this model was selected over alternatives (e.g., quantile regression). Additionally, please clarify whether survey weights and clustering were fully accounted for in all regression analyses.

Response: Thank you for the recommendation. We agree that several modeling strategies may be used for skewed outcomes. However, our research question focused on estimating the association between RFM and the Framingham Risk Score. For this purpose, a generalized linear model with a gamma family and log link was selected because it models the conditional mean of a positively skewed continuous outcome and provides multiplicative, population-averaged estimates, which are appropriate for addressing this type of association. Quantile regression, while valuable for examining how an exposure affects specific quantiles of the outcome distribution, addresses a different scientific question and is not designed to estimate mean associations. Because our study did not aim to investigate distributional differences across percentiles, quantile regression was not the optimal analytic approach. Additionally, for quantile regression STATA statistical package does not account for the complex survey weights. This would yield imprecise estimates given the national survey we used, and thus represents a limitation.

Regarding the use of survey weights and the complex survey design in regression models we would like to note that in the submitted manuscript we declared in the Statistical Analysis section that “Given the characteristics of the VIANEV survey, the analyses accounted for sample weights and the complex survey design”. Furthermore, for further clarity Table 3 has a footnote stating this, and it reads “All estimates accounted for the VIANEV sample design”

Changes: None

6. Potential Confounders

-Important confounders such as alcohol consumption, physical activity beyond sedentary time, and dietary quality were not included. The absence of these variables should be acknowledged as a limitation in more detail.

Response: Thank you for the observation. When selecting potential confounding variables for our models, we considered including alcohol consumption, which is available in the dataset (alcohol use during the past 30 days). Initially, we decided not to include it because our primary focus was on variables most directly related to adiposity and cardiometabolic risk; however, we agree that alcohol consumption is an important behavioral factor. Based on your suggestion, we have now incorporated alcohol consumption into all adjusted models (see revised Tables 1, 2, and 3). After inclusion, the coefficients remained virtually unchanged, with only one estimate showing a minimal increase (from 0.47 [0.32–0.63] to 0.48 [0.32–0.63]), indicating that alcohol consumption did not materially alter the associations.

Regarding physical activity, we opted to adjust for sedentary time because prolonged sitting is independently associated with adverse cardiometabolic outcomes, even among individuals who meet physical activity recommendations (1). Sedentary behavior therefore captures a distinct and relevant dimension of movement-related exposure. Nonetheless, we acknowledge that the absence of more detailed physical activity indicators may result in residual confounding. No dietary quality data was available for which we did not include this as a confounding variable.

1. Liang, Zhi-de et al. “Association between sedentary behavior, physical activity, and cardiovascular disease-related outcomes in adults-A meta-analysis and systematic review.” Frontiers in public health vol. 10 1018460. 19 Oct. 2022, doi:10.3389/fpubh.2022.1018460

Changes: Following your recommendation, we have added the following to our limitations section:

“The lack of potentially confounding variables, such as diet quality, energy intake or more specific physical activity measurement, could also result in residual confounding, affecting the magnitude and direction of the estimated associations due to its strong influence on body fat percentage and components of the Framingham Risk Score; nevertheless, the adjustment models included indirect measures of diet quality (daily consumption of five or more portions of fruits and vegetables) and physical activity (daily hours of sedentary behavior) in order to reduce confounding.”

7. Sex-Specific Findings

- The stronger association in women is intriguing. The Discussion offers some explanations (biological and social), but these remain speculative. The authors should expand on possible mechanisms and highlight the need for future longitudinal research to clarify causality.

Response: Thank you for the observation. We agree with the reviewer’s observation and have incorporated a text addressing this topic.

Changes: The following text was added in the discussion section:

“Additionally, our findings show a stronger association between obesity and cardiovascular risk in women, which is consistent with evidence indicating a higher burden of cardiovascular risk factors in women compared to men [38]. In Peru, studies have similarly reported a higher prevalence of obesity and metabolic syndrome among women [39,40]. Likewise, an analysis of the nationally representative ENDES 2019 survey found that women had markedly higher odds of abdominal obesity than men, reinforcing the notion of sex-specific vulnerability in adiposity-related cardiometabolic risk [40]. Together, these findings provide context for why increases in RFM may correspond to larger relative changes in predicted 10-year cardiovascular risk among women in our study.

In line with this, biological factors, such as greater susceptibility to chronic diseases and the interaction between estrogens and age, as well as social factors including disparities in the detection and treatment of CVD, could also explain women’s higher vulnerability [38]. On the other hand, epidemiological studies in Latin America [4] have reported a higher incidence of CVD in men than in women (655 vs. 531 per 100,000 individuals), and additional evidence indicates that Peruvian men present worse cardiovascular health than women [5,41]. Of note, compared with previous re

Attachment

Submitted filename: RESPONSE LETTER RFM FRSCORE.docx

pone.0343062.s002.docx (26.7KB, docx)

Decision Letter 1

Neftali Eduardo Antonio-Villa

4 Jan 2026

Dear Dr. Hernández-Vásquez,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Feb 18 2026 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org . When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

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Neftali Eduardo Antonio-Villa, MD PhD

Academic Editor

PLOS One

Journal Requirements:

If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise.

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

Reviewer #1: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions??>

Reviewer #1: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously? -->?>

Reviewer #1: I Don't Know

**********

4. Have the authors made all data underlying the findings in their manuscript fully available??>

The PLOS Data policy

Reviewer #1: (No Response)

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #1: Yes

**********

Reviewer #1: 1. Novelty and Framing of Contribution

Although the authors now acknowledge ethnic and body composition differences in the Introduction, the unique contribution of this study remains under-emphasized.

- The manuscript would benefit from a clearer statement of contribution beyond “first in Peru.”

- Specifically, the authors should emphasize:

- The comparison of multiple operationalizations of RFM (binary, continuous, tertiles)

- The sex-stratified modeling with complex survey adjustment

Recommendation:

Add 1–2 sentences in the final paragraph of the Introduction explicitly stating how this study advances knowledge beyond prior international RFM studies.

2. Use of the Framingham Risk Score

The authors appropriately acknowledge the lack of local validation and justify the use of the Framingham score due to Ministry of Health endorsement. However:

- The manuscript still risks being interpreted as estimating true cardiovascular risk rather than relative predicted risk.

- Some phrasing in the Results and Discussion (e.g., “higher cardiovascular risk”) could be misinterpreted by readers unfamiliar with risk score limitations.

Recommendation:

Systematically use wording such as “higher estimated 10-year cardiovascular risk” or “higher Framingham risk score” throughout the Results and Discussion to avoid overinterpretation.

3. Interpretation of Effect Sizes from Gamma GLM

The use of β coefficients from a log-linked gamma model is statistically sound, but interpretability remains limited for non-technical readers.

- While the authors chose not to report prevalence ratios, readers may still struggle to understand the clinical relevance of coefficients such as β = 0.48.

- The newly added absolute mean differences are helpful but underutilized.

Recommendation:

In the Discussion, briefly interpret at least one adjusted estimate in plain language (e.g., relative or proportional increase in Framingham score) to improve accessibility.

4. Sex-Specific Findings

The expanded discussion on sex differences is thoughtful and well-referenced. However:

- The section is now quite long and diffuse, mixing Peruvian data, regional incidence, and methodological distinctions between predicted risk and observed events.

- Some arguments appear defensive rather than explanatory.

Recommendation:

Condense this section slightly and clearly separate:

1.Biological/social explanations

2.Differences between predicted risk and observed incidence

3.Implications for future longitudinal research

This will improve coherence and readability.

**********

what does this mean? ). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

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Reviewer #1: No

**********

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PLoS One. 2026 Feb 23;21(2):e0343062. doi: 10.1371/journal.pone.0343062.r004

Author response to Decision Letter 2


6 Jan 2026

Response Letter - Round 2

Reviewer #1:

1. Novelty and Framing of Contribution

Although the authors now acknowledge ethnic and body composition differences in the Introduction, the unique contribution of this study remains under-emphasized.

- The manuscript would benefit from a clearer statement of contribution beyond “first in Peru.”

- Specifically, the authors should emphasize:

- The comparison of multiple operationalizations of RFM (binary, continuous, tertiles)

- The sex-stratified modeling with complex survey adjustment

Recommendation:

Add 1–2 sentences in the final paragraph of the Introduction explicitly stating how this study advances knowledge beyond prior international RFM studies.

Response:

We thank the reviewer for this important observation. We agree that our contribution extends beyond being the first study in Peru and should highlight the methodological advances and analytical approach that distinguish our work from previous international studies. We have revised the final paragraph of the Introduction to better articulate these specific contributions.

Change:

Now the text reads: Therefore, this study aimed to evaluate the association between obesity defined by RFM, considered under different operationalization approaches (binary, continuous, and tertile-based) and 10-year cardiovascular risk stratified by sex, as estimated by the Framingham score in Peruvian adults who participated in a national survey during 2017–2018. The present study advances knowledge beyond prior international RFM studies by comparing multiple operationalizations of RFM (binary, continuous, and tertiles) and applying sex-stratified analyses within a complex survey design in a nationally representative Latin American population, providing novel insights into optimal analytical strategies for RFM-cardiovascular risk assessment in ethnically diverse contexts.

2. Use of the Framingham Risk Score

The authors appropriately acknowledge the lack of local validation and justify the use of the Framingham score due to Ministry of Health endorsement. However:

- The manuscript still risks being interpreted as estimating true cardiovascular risk rather than relative predicted risk.

- Some phrasing in the Results and Discussion (e.g., “higher cardiovascular risk”) could be misinterpreted by readers unfamiliar with risk score limitations.

Recommendation:

Systematically use wording such as “higher estimated 10-year cardiovascular risk” or “higher Framingham risk score” throughout the Results and Discussion to avoid overinterpretation.

Response:

We thank the reviewer for this observation. We fully agree that our terminology must clearly distinguish between predicted risk scores and actual cardiovascular risk, especially given the lack of local validation of the Framingham score in Peruvian populations.

Change:

We have made changes to the Results and Discussion sections to explicitly specify that the outcome refers to “risk.”

3. Interpretation of Effect Sizes from Gamma GLM

The use of β coefficients from a log-linked gamma model is statistically sound, but interpretability remains limited for non-technical readers.

- While the authors chose not to report prevalence ratios, readers may still struggle to understand the clinical relevance of coefficients such as β = 0.48.

- The newly added absolute mean differences are helpful but underutilized.

Recommendation:

In the Discussion, briefly interpret at least one adjusted estimate in plain language (e.g., relative or proportional increase in Framingham score) to improve accessibility.

Response:

We thank the reviewer for this observation. We agree with the suggestion and have added a plain-language interpretation in the first paragraph of the Discussion section.

Change:

The objective of the present study was to evaluate the association between obesity defined by RFM and the estimated 10-year cardiovascular risk according to estimated through the Framingham risk score in Peruvian adults aged 30 to 59 years. A positive and significant association was observed in both sexes. Furthermore, it was found that for each unit increase in RFM, the estimated cardiovascular risk Framingham risk score increased by 0.07 in men and 0.06 in women, corresponding to approximately 7% and 6% higher estimated risk, respectively. This indicates that higher estimated total body fat percentage is associated with proportionally higher estimated 10-year cardiovascular risk indicating that for each increase in the estimated total body fat percentage, the estimated 10-year cardiovascular risk also increases. To the best of our knowledge, this is the first study to evaluate the association between RFM, an alternative estimator of total body fat percentage, and the estimated 10-year cardiovascular risk using the Framingham risk score.

4. Sex-Specific Findings

The expanded discussion on sex differences is thoughtful and well-referenced. However:

- The section is now quite long and diffuse, mixing Peruvian data, regional incidence, and methodological distinctions between predicted risk and observed events.

- Some arguments appear defensive rather than explanatory.

Recommendation:

Condense this section slightly and clearly separate:

1.Biological/social explanations

2.Differences between predicted risk and observed incidence

3.Implications for future longitudinal research

This will improve coherence and readability.

Response:

We thank the reviewer for this observation. We have thoroughly reviewed the content of the Discussion section, which was was refined and reorganized to improve coherence and readability with added subheadings to facilitate identification of the following sections:

1) Comparison with previous studies

2) Potential explanatory mechanisms

3) Sex-based differences

4) Implications for public health and clinical practice

5) Study limitations.

Changes: The discussion section has been revised. The sex-specific findings section was refined and reorganized to improve clarity.

Attachment

Submitted filename: 1. Response Letter R2.docx

pone.0343062.s003.docx (285.8KB, docx)

Decision Letter 2

Neftali Eduardo Antonio-Villa

22 Jan 2026

Dear Dr. Hernández-Vásquez,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Mar 08 2026 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org . When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

  • A letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

  • A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

  • An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols . Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols .

We look forward to receiving your revised manuscript.

Kind regards,

Neftali Eduardo Antonio-Villa, MD PhD

Academic Editor

PLOS One

Journal Requirements:

1. If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise.

2. Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Additional Editor Comments:

Please address the comments raised by the reviewer. In particular, emphasize the consistency of the findings between the abstract and conclusions, justify the selection of confounders, and soften the tone of any inferential conclusions.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

Reviewer #1: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions??>

Reviewer #1: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously? -->?>

Reviewer #1: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available??>

The PLOS Data policy

Reviewer #1: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #1: Yes

**********

Reviewer #1: Comments

1. Clarification of Outcome Interpretation

The authors have appropriately revised much of the text to emphasize “estimated 10-year cardiovascular risk” rather than true event risk. However, a small number of phrases still risk causal or clinical overinterpretation, particularly in the Abstract and Conclusion where statements such as “higher cardiovascular risk” appear without explicit reference to prediction.

Recommendation:

- Perform a final consistency check across the Abstract, Results, Discussion, and Conclusion to ensure uniform use of terms such as “higher Framingham risk score” or “higher estimated 10-year cardiovascular risk.”

This will further reduce the risk of misinterpretation by non-specialist readers.

2. Interpretation of Effect Sizes in Log-Gamma Models

The added plain-language interpretation of the continuous RFM coefficients (e.g., ~6–7% higher estimated risk per unit increase) is a valuable improvement. However, the interpretation currently appears only once and is not clearly tied to the categorical (binary and tertile-based) analyses.

Recommendation:

- Briefly contextualize at least one categorical comparison (e.g., obese vs. non-obese or highest vs. lowest tertile) in relative or proportional terms in the Discussion.

This would enhance accessibility for readers unfamiliar with generalized linear models while preserving statistical rigor.

3. Cross-sectional Design and Temporality

Although the limitations section appropriately acknowledges the cross-sectional nature of the data, some statements in the Discussion (particularly in the mechanistic and public health implications sections) still imply directionality between adiposity and cardiovascular risk.

Recommendation:

- Slightly temper causal language when referring to mechanisms or implications (e.g., “may contribute to” rather than “leads to”).

- Explicitly reiterate that associations reflect concurrent relationships with predicted risk rather than disease progression.

4. Sex-Stratified Analyses

The reorganization of the Discussion into sub-sections has improved clarity. The section on sex-based differences is now more balanced and less defensive. However, it remains relatively long compared to other sections.

Recommendation:

- Consider further condensation by reducing repetition between regional epidemiology and methodological explanations of predicted versus observed risk.

5. Covariate Selection and Residual Confounding

The rationale for covariate selection is reasonable and consistent with epidemiological standards. However, diet and physical activity are only indirectly captured.

Recommendation:

- Add a brief sentence in the Methods or Limitations explicitly stating that residual confounding related to unmeasured dietary quality and physical activity intensity cannot be excluded.

6. Presentation of Tables

Tables are generally clear and informative. However, Table 2 is dense and may be difficult to interpret for readers.

Recommendation:

- Consider adding a brief interpretive sentence in the Results highlighting the most salient gradients (e.g., age and altitude trends) rather than relying solely on tabular detail.

**********

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Reviewer #1: No

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PLoS One. 2026 Feb 23;21(2):e0343062. doi: 10.1371/journal.pone.0343062.r006

Author response to Decision Letter 3


28 Jan 2026

Response Letter - Round 3

Reviewer #1:

1. Clarification of Outcome Interpretation

The authors have appropriately revised much of the text to emphasize “estimated 10-year cardiovascular risk” rather than true event risk. However, a small number of phrases still risk causal or clinical overinterpretation, particularly in the Abstract and Conclusion where statements such as “higher cardiovascular risk” appear without explicit reference to prediction.

Recommendation:

- Perform a final consistency check across the Abstract, Results, Discussion, and Conclusion to ensure uniform use of terms such as “higher Framingham risk score” or “higher estimated 10-year cardiovascular risk.”

This will further reduce the risk of misinterpretation by non-specialist readers.

Response: We thank the reviewer for this observation.

Changes: Revisions have been made throughout the manuscript in accordance with the recommendations.

2. Interpretation of Effect Sizes in Log-Gamma Models

The added plain-language interpretation of the continuous RFM coefficients (e.g., ~6–7% higher estimated risk per unit increase) is a valuable improvement. However, the interpretation currently appears only once and is not clearly tied to the categorical (binary and tertile-based) analyses.

Recommendation:

- Briefly contextualize at least one categorical comparison (e.g., obese vs. non-obese or highest vs. lowest tertile) in relative or proportional terms in the Discussion.

This would enhance accessibility for readers unfamiliar with generalized linear models while preserving statistical rigor.

Response: Thank you for the clarification. We have incorporated these recommendations into the Discussion section.

Changes: We added interpretations in proportional terms, as well as interpretations of the results stratified by tertiles.

3. Cross-sectional Design and Temporality

Although the limitations section appropriately acknowledges the cross-sectional nature of the data, some statements in the Discussion (particularly in the mechanistic and public health implications sections) still imply directionality between adiposity and cardiovascular risk.

Recommendation:

- Slightly temper causal language when referring to mechanisms or implications (e.g., “may contribute to” rather than “leads to”).

- Explicitly reiterate that associations reflect concurrent relationships with predicted risk rather than disease progression.

Response: We thank the reviewer for this observation. We revised the Discussion to further temper causal language, particularly in the sections addressing potential mechanisms and public health implications.

Changes: Revisions have been made throughout the manuscript in accordance with the recommendations. Relevant statements were rephrased to emphasize that our findings reflect concurrent associations between RFM-defined adiposity and estimated 10-year cardiovascular risk, rather than causal effects or disease progression.

4. Sex-Stratified Analyses

The reorganization of the Discussion into sub-sections has improved clarity. The section on sex-based differences is now more balanced and less defensive. However, it remains relatively long compared to other sections.

Recommendation:

- Consider further condensation by reducing repetition between regional epidemiology and methodological explanations of predicted versus observed risk.

Response: Thank you for the clarification. We agree that this section is relatively lengthy.

Change: We have synthesized the main ideas of this subsection while preserving the key message we aim to convey to readers.

5. Covariate Selection and Residual Confounding

The rationale for covariate selection is reasonable and consistent with epidemiological standards. However, diet and physical activity are only indirectly captured.

Recommendation:

- Add a brief sentence in the Methods or Limitations explicitly stating that residual confounding related to unmeasured dietary quality and physical activity intensity cannot be excluded.

Response: Thank you for the clarification. We agree that it is important to explicitly state that adjustment for these variables does not exclude residual confounding.

Changes: We have clarified this in the Limitations section.

6. Presentation of Tables

Tables are generally clear and informative. However, Table 2 is dense and may be difficult to interpret for readers.

Recommendation:

- Consider adding a brief interpretive sentence in the Results highlighting the most salient gradients (e.g., age and altitude trends) rather than relying solely on tabular detail.

Response: Thank you for the clarification regarding synthesizing the findings of Table 2 in the Results section.

Changes: We have made changes to the interpretation of the findings.

Attachment

Submitted filename: Response Letter R3.docx

pone.0343062.s004.docx (285.2KB, docx)

Decision Letter 3

Neftali Eduardo Antonio-Villa

1 Feb 2026

Relative fat mass and cardiovascular risk in Peruvian adults: Findings from a national survey

PONE-D-25-46369R3

Dear Dr. Hernández-Vásquez,

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Academic Editor

PLOS One

Additional Editor Comments (optional):

Thank you for addressing all of the referees’ comments. I read the revised manuscript with great interest, and I believe it fills an important research gap in Peru. I congratulate the authors and look forward to seeing future work on this topic from the study group.

Reviewers' comments:

Acceptance letter

Neftali Eduardo Antonio-Villa

PONE-D-25-46369R3

PLOS One

Dear Dr. Hernández-Vásquez,

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Academic Editor

PLOS One

Associated Data

    This section collects any data citations, data availability statements, or supplementary materials included in this article.

    Supplementary Materials

    Attachment

    Submitted filename: RESPONSE LETTER RFM FRSCORE.docx

    pone.0343062.s002.docx (26.7KB, docx)
    Attachment

    Submitted filename: 1. Response Letter R2.docx

    pone.0343062.s003.docx (285.8KB, docx)
    Attachment

    Submitted filename: Response Letter R3.docx

    pone.0343062.s004.docx (285.2KB, docx)

    Data Availability Statement

    The dataset is accessible through the Peruvian National Open Data Platform (https://www.datosabiertos.gob.pe/dataset/estado-nutricional-en-adultos-de-18-59-a%C3%B1os-per%C3%BA-2017-%E2%80%93-2018). Similarly, ENAHO data are publicly available at https://proyectos.inei.gob.pe/microdatos/.


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