Health risk assessment method for association of PFAS concentration and cardiovascular-kidney-metabolic syndrome

Abstract

The invention discloses a health risk assessment method for association of PFAS concentration and cardiovascular-kidney-metabolic syndrome, and the method comprises the following specific implementation processes: obtaining concentration data of PFAS in serum of a crowd and related data of blood physicochemical and physicochemical measurement, and calculating the ten-year cardiovascular disease risk and renal function condition of a human body. The heart and kidney metabolic syndrome condition of an individual is staging to judge the health condition, and a threshold value of health risk improvement is established according to the serum PFAS concentration and related data of all samples in combination with the health condition. According to the method, accurate quantitative evaluation of multi-dimensional health risks is realized, the comprehensive influence of PFAS on human health is more comprehensively reflected through the heart and kidney metabolic syndrome, the health risk threshold of serum PFAS exposure is provided, and early warning is provided for high-risk people.

Description

Technical Field

[0001] This invention belongs to the field of environmental health risk assessment technology, specifically relating to a health risk assessment method for the association of PFAS concentration with cardiovascular-renal-metabolic syndrome. Background Technology

[0002] PFAS (perfluoroalkyl substances) are widely used in textiles, food packaging, non-stick coatings, and fire-fighting foams. The carbon-fluorine bonds in PFAS make them highly persistent in the environment, accumulating in the human body through drinking water, the food chain, and dust exposure. Once in the bloodstream, PFAS bind to plasma proteins, are difficult to metabolize, and have half-lives of 3-7 years or even decades. PFAS exposure is closely related to multi-system health damage in the human body, involving cardiovascular disease, chronic kidney disease, metabolic disorders, and other aspects. Therefore, there is an urgent need to establish a method for assessing the health risks posed by PFAS in the blood.

[0003] However, traditional research often focuses on a single disease endpoint (such as hypertension, diabetes, or decreased kidney function), which makes it difficult to comprehensively characterize the complex effects and risk dynamics of PFAS on multiple organ systems in the human body, limiting the comprehensive assessment of their health hazards and the ability to provide early warning. Current research perspectives are more focused on exploring the association between single PFAS compounds and specific health indicators (such as blood lipids, blood glucose, and glomerular filtration rate). While this provides important toxicological clues, it is far from sufficient to assess the complex cardiorenal metabolic interaction network induced by PFAS and its overall health risks. As an organic whole, the effects of PFAS exposure on the human body are often synergistic or antagonistic effects across multiple targets and pathways; a single indicator is insufficient to reflect the process and severity of such systemic damage. Summary of the Invention

[0004] This invention addresses the shortcomings of existing assessment technologies by providing a health risk assessment method for the association between PFAS concentration and cardiovascular-renal-metabolic syndrome. This method uses blood physiochemical indicators and physical measurements to determine health indicators, constructs a model based on serum PFAS concentration, and provides an effect curve and health risk threshold.

[0005] The specific technical solution is as follows:

[0006] A method for assessing the health risk associated with PFAS concentration and cardiovascular-renal-metabolic syndrome includes the following steps:

[0007] 1) Obtain data on the concentration of PFAS in the serum of the population and related data on blood physicochemical and anthropometric measurements;

[0008] 2) Calculate the human body's ten-year cardiovascular disease risk and kidney function status;

[0009] 3) Stage the individual's cardiorenal metabolic syndrome to assess their health status;

[0010] 4) Based on the serum PFAS concentration and related data of all samples, establish a threshold for increased health risk in conjunction with health status.

[0011] Further, the relevant data for blood physiochemical and physical tests in step 1) include age, sex, waist circumference, blood glucose, blood pressure, whether antihypertensive drugs are being taken, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, whether diabetes is present, whether smoking is present, estimated glomerular filtration rate, body mass index, glycated hemoglobin, urine albumin to creatinine ratio, creatinine level, and serum triglycerides.

[0012] Furthermore, the estimated glomerular filtration rate was calculated using the CDK-EPI 2021 formula, as follows:

[0013] eGFR = 142x(Scr / A) B x(0.9938) age x C

[0014] In the formula: Scr is the creatinine level, mg / dL; age is age; for women, the C value is 1.012, when Scr≤0.7mg / dL, A=0.7, B=-0.241, when Scr>0.7mg / dL, A=0.7, B=-1.2; for men, the C value is 1, when Scr≤0.9mg / dL, A=0.9, B=-0.302, when Scr>0.9mg / dL, A=0.9, B=-1.2.

[0015] Further, in step 2), the ten-year cardiovascular disease risk is calculated using the PREVENT equation, and renal function is assessed based on the estimated glomerular filtration rate (eGFR). When eGFR ≥ 90 mL / (min·1.73 mcg), the risk is considered lower. 2 If the subject is asymptomatic, renal function is considered normal; when 60 ≤ eGFR < 90 mL / (min·1.73m 2 When 30 ≤ eGFR < 60 mL / (min·1.73m), renal function is considered mildly impaired; when 30 ≤ eGFR < 60 mL / (min·1.73m 2 If the renal function is 15 ≤ eGFR < 30 mL / (min·1.73m), then the renal function is considered moderately decreased; 2 If the eGFR is <15 mL / (min·1.73 mcg), then renal function is considered severely impaired; 2 If the condition is as described above, then kidney failure is diagnosed.

[0016] Furthermore, in step 3), the criteria for determining the comprehensive cardiorenal metabolic index are as follows:

[0017] Phase 0: No risk factors, with a normal BMI < 23 kg / m² 2 Normal waist circumference (women <80cm, men <90cm), normal blood sugar, normal blood pressure, normal blood lipid levels, and no evidence of chronic kidney disease or subclinical or clinical cardiovascular disease.

[0018] Phase 1: Individuals who are overweight / obese, have abdominal obesity, or adipose tissue dysfunction, but have no other metabolic risk factors or chronic kidney disease. Specific criteria include: BMI ≥ 23 kg / m². 2 Stage 1: Women with a waist circumference ≥80cm, men with a waist circumference ≥90cm; fasting blood glucose ≥100mg / dL; glycated hemoglobin between 5.7% and 6.4%; Stage 2: Fasting serum triglyceride level ≥135mg / dL, hypertension, diabetes or metabolic syndrome. Metabolic syndrome is defined as having three or more of the following symptoms: increased waist circumference, LDL cholesterol level <40mg / dL for men, LDL cholesterol level <50mg / dL for women, fasting serum triglycerides ≥150mg / dL, systolic blood pressure ≥130mmHg, diastolic blood pressure ≥80mmHg, use of antihypertensive drugs, prediabetes.

[0019] Stage 3: Severe decline in renal function or renal failure, or a ten-year cardiovascular disease risk value ≥20%; Stage 4: Diagnosis of cardiovascular disease, including coronary heart disease, angina pectoris, myocardial infarction, heart failure, and stroke.

[0020] Further, step 4) involves constructing a risk-exposure model using a generalized additive model (GAM). A reference dose is defined to calculate the baseline risk, typically the detection limit of PFAS in human serum. A trained GAM model is used to predict the baseline risk of high-stage cardiorenal metabolic syndrome at the reference dose. The baseline dose-based median risk (BMD) method is used to calculate the threshold: Target risk probability = Baseline risk + BMR × (1 - Baseline risk), where BMR is a specific dose level, set at 10%, representing the likelihood of high-stage cardiorenal metabolic syndrome in 10% of the population. The GAM model is used to predict the response probability of the entire population. The absolute distance between all predicted probabilities and the target risk probability is calculated, and the dose value whose predicted probability is closest to the target probability is found; this is the BMD. 10 Calculate BMD 10 Confidence interval, BMDL 10 It is BMD 10 The 95% confidence lower limit, used to cover experimental variability and model uncertainty, can represent the health threshold that causes 10% of the population to develop high-stage cardiorenal metabolic syndrome.

[0021] The beneficial effects of this invention are: to achieve accurate quantitative assessment of multi-dimensional health risks, to more comprehensively reflect the comprehensive impact of PFAS on human health through "cardiorenal metabolic syndrome", to propose a health risk threshold for serum PFAS exposure, and to provide early warning for high-risk groups. Attached Figure Description

[0022] Figure 1 This is a schematic diagram of the process of the present invention. Detailed Implementation

[0023] The present invention will be further described below with reference to the accompanying drawings and specific embodiments, but the scope of protection of the present invention is not limited thereto.

[0024] like Figure 1 As shown, a health risk assessment method for the association between PFAS concentration and cardiovascular-renal-metabolic syndrome includes the following steps:

[0025] 1. Concentration data of perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorononanoic acid (PFNA), and perfluorohexane sulfonic acid (PFHxS) in the serum of 7014 individuals were obtained, along with detailed data on blood physicochemical and anthropometric measurements.

[0026] 2. The estimated glomerular filtration rate (GFR) of participants was calculated using the CDK-EPI formula, and the ten-year cardiovascular disease risk was calculated using the PREVENT equation. The estimated GFR was calculated using the CDK-EPI formula, as follows:

[0027] eGFR = 142x(Scr / A) B x(0.9938) age x C

[0028] In the formula: Scr is the creatinine level, mg / dL; age is age; for women, the C value is 1.012, when Scr≤0.7mg / dL, A=0.7, B=-0.241, when Scr>0.7mg / dL, A=0.7, B=-1.2; for men, the C value is 1, when Scr≤0.9mg / dL, A=0.9, B=-0.302, when Scr>0.9mg / dL, A=0.9, B=-1.2.

[0029] 3. Based on the obtained data, the stage of cardiorenal metabolic syndrome for all individuals was determined according to the staging criteria, and the stage of syndrome was marked with the corresponding number.

[0030] Data from some participants are shown in Table 1:

[0031] Table 1 shows data for some participants.

[0032]

[0033]

[0034] 4. The cardio-renal-metabolic syndrome stages were transformed into binary variables, with stages 0 and 1 serving as low-risk controls and stages 2, 3, and 4 as positive controls. A generalized additive model (g(E(Y)) = α + s1(x1) + ... + sp(xp), where Y is the dependent variable (i.e., the variable to be predicted), E(Y) represents the expected value, and g(Y) represents the link function that connects the expected value with the predicted variables s1(x1), ..., sp(xp)) was used to fit the dose-response relationship between serum PFAS concentration and cardio-renal-metabolic syndrome. This model used cubic regression splines to fit the nonlinear relationship of dose-response. The basic dimension k = 6 was set to control the model complexity. A quasi-binomial distribution family was used to process the discrete binary data. The smoothing parameters were optimized by restricted maximum likelihood. The dose-response curve was given based on the model results, and the inflection point of the curve was found using the maximum likelihood method. A reference dose of 0.07 ng / ml (the detection limit of serum PFAS in this data) was defined to calculate baseline risk. A trained GAM model was used to predict the baseline risk of developing stage 2, 3, and 4 cardiorenal metabolic syndrome at the reference dose. The baseline dose (BMD) method was used to calculate the threshold: Target risk probability = Baseline risk + BMR × (1 - Baseline risk), where BMR is a specific dose level, set at 10%, representing the likelihood of inducing high-stage cardiorenal metabolic syndrome in 10% of the population. The GAM model was used to predict the response probability of the entire population. The absolute distance between all predicted probabilities and the target risk probability was calculated, and the dose value whose predicted probability was closest to the target probability was found, i.e., the BMD. 10 BMD constructed based on prediction standard error 10 Confidence interval, BMDL 10 It is BMD 10 The 95% confidence lower limit, used to cover experimental variability and model uncertainty, can represent the health threshold that causes 10% of the population to develop high-stage cardiorenal metabolic syndrome.

[0035] BMD of the model 10 The confidence intervals were: PFHxS = 1.56 (1.29-2.62) ng / ml, PFNA = 0.49 (0.38-0.61) ng / ml, PFOS = 6.56 (5.65-7.57) ng / ml, PFOA = 2.91 (2.09-3.58) ng / ml.

[0036] The exposure dose concentration thresholds for PFAS in serum that cause high-risk cardiorenal metabolic syndrome (stages 2-4) in 10% of the population are PFHxS = 1.29 ng / ml, PFNA = 0.38 ng / ml, PFOS = 5.65 ng / ml, and PFOA = 2.09 ng / ml.

Claims

1. A method for assessing the health risk associated with PFAS concentration and cardiovascular-renal-metabolic syndrome, characterized in that, Includes the following steps: 1) Obtain data on the concentration of PFAS in the serum of the population and related data on blood physicochemical and anthropometric measurements; 2) Calculate the human body's ten-year cardiovascular disease risk and kidney function status; 3) Stage the individual's cardiorenal metabolic syndrome to assess their health status; 4) Based on the serum PFAS concentration and related data of all samples, establish a threshold for increased health risk in conjunction with health status.

2. The health risk assessment method for the association between PFAS concentration and cardiovascular-renal-metabolic syndrome as described in claim 1, characterized in that, The relevant data for blood physiochemical and physical tests in step 1) include age, sex, waist circumference, blood glucose, blood pressure, whether antihypertensive drugs are being taken, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, whether diabetes is present, whether smoking is present, estimated glomerular filtration rate, body mass index, glycated hemoglobin, urine albumin to creatinine ratio, creatinine level, and serum triglycerides.

3. The health risk assessment method for the association between PFAS concentration and cardiovascular-renal-metabolic syndrome as described in claim 2, characterized in that, The estimated glomerular filtration rate was calculated using the CDK-EPI 2021 formula, as follows: eGFR=142x(Scr / A) B x(0.9938) age x C In the formula: Scr is the creatinine level, mg / dL; age is age; for women, the C value is 1.012, when Scr≤0.7mg / dL, A=0.7, B=-0.241, when Scr>0.7mg / dL, A=0.7, B=-1.2; for men, the C value is 1, when Scr≤0.9mg / dL, A=0.9, B=-0.302, when Scr>0.9mg / dL, A=0.9, B=-1.

2.

4. The health risk assessment method for the association between PFAS concentration and cardiovascular-renal-metabolic syndrome as described in claim 3, characterized in that, Step 2) uses the PREVENT equation to calculate the ten-year cardiovascular disease risk, and assesses renal function based on the estimated glomerular filtration rate (eGFR). When eGFR ≥ 90... mL / (min·1.73m 2 If the subject is asymptomatic, renal function is considered normal; when 60 ≤ eGFR < 90 mL / (min·1.73m 2 If the eGFR is 30 ≤ eGFR < 30, then the kidney function is considered to be mildly decreased; if the eGFR is 30 ≤ eGFR < 30, then the kidney function is considered to be mildly decreased. 60mL / (min·1.73m 2 If the renal function is moderately decreased (eGFR < 30), then the renal function is considered moderately decreased. mL / (min·1.73m 2 If the eGFR is <15 mL / (min·1.73 mcg), then renal function is considered severely impaired; 2 If the condition is as described above, then kidney failure is diagnosed.

5. The health risk assessment method for the association between PFAS concentration and cardiovascular-renal-metabolic syndrome as described in claim 4, characterized in that, In step 3), the criteria for judging the cardiorenal metabolic index are as follows: Stage 0: No risk factors, with a normal BMI < 23 kg / m². 2 Normal waist circumference (women <80cm, men <90cm), normal blood sugar, normal blood pressure, normal blood lipid levels, and no evidence of chronic kidney disease or subclinical or clinical cardiovascular disease. Phase 1: Individuals who are overweight / obese, have abdominal obesity, or adipose tissue dysfunction, but have no other metabolic risk factors or chronic kidney disease. Specific criteria include: BMI ≥ 23 kg / m². 2 Women with a waist circumference ≥80cm and men with a waist circumference ≥90cm; fasting blood glucose ≥100mg / dL; glycated hemoglobin between 5.7% and 6.4%; Stage 2: Fasting serum triglyceride level ≥135mg / dL, hypertension, diabetes, or metabolic syndrome. Metabolic syndrome is defined as having three or more of the following symptoms: increased waist circumference, LDL cholesterol level <40mg / dL in men, LDL cholesterol level <50mg / dL in women, fasting serum triglyceride ≥150mg / dL, systolic blood pressure ≥130mmHg, diastolic blood pressure ≥80mmHg, use of antihypertensive drugs, or prediabetes. Stage 3: Severe decline in renal function or renal failure, or a ten-year cardiovascular disease risk value ≥20%; Stage 4: Diagnosis of cardiovascular disease, including coronary heart disease, angina pectoris, myocardial infarction, heart failure, and stroke.

6. The health risk assessment method for the association between PFAS concentration and cardiovascular-renal-metabolic syndrome as described in claim 5, characterized in that, Step 4) involves constructing a risk-exposure model using a generalized additive model (GAM). A reference dose is defined to calculate the baseline risk, typically the detection limit of PFAS in human serum. A trained GAM model is used to predict the baseline risk of developing high-stage cardiorenal metabolic syndrome at the reference dose. The baseline dose-based median risk (BMD) method is used to calculate the threshold: Target risk probability = Baseline risk + BMR × (1 - Baseline risk), where BMR is a specific dose level, set at 10%, representing the likelihood of inducing high-stage cardiorenal metabolic syndrome in 10% of the population. The GAM model is then used to predict the response probability of the entire population. The absolute distance between all predicted probabilities and the target risk probability is calculated, and the dose value whose predicted probability is closest to the target probability is found; this is the BMD. 10 Calculate BMD 10 Confidence interval, BMDL 10 It is BMD 10 The 95% confidence lower limit, used to cover experimental variability and model uncertainty, can represent the health threshold that causes 10% of the population to develop high-stage cardiorenal metabolic syndrome.

Images