Parental educational status independently predicts the risk of prevalent hypertension in young adults

Identification of individuals at risk of hypertension development based on socio-economic status have been inconclusive, due to variable definitions of low socio-economic status. We investigated whether educational status of individuals or their parents predicts prevalent hypertension in young adult population, by analyzing data of more than 37,000 non-institutionalized subjects from Korea National Health and Nutrition Examination Survey 2008 to 2017. Although low educational status of individual subjects was robustly associated with elevation of systolic blood pressure and increased prevalence of hypertension in general population, its impact on prevalent hypertension differed across age subgroups, and was remarkably attenuated in young adults. Parental educational status was significantly associated with prevalent hypertension in young adults, but not or only marginally in elderly population. Low parental educational status was also associated with high sodium intake in young adults, irrespective of subject’s own educational status. These collectively indicate that parental educational status, rather than individual’s own educational status, better and independently predicts prevalent hypertension in young adults, and that young adults with low parental educational status are prone to intake more sodium, possibly contributing to the increased risk of hypertension development. We expect that our findings could help define young individuals at risk of high sodium intake and hypertension.


Results
Baseline characteristics of study subjects by educational status. To address the baseline characteristics according to educational status, study subjects were divided by educational years into 4 subgroups ( Table 1). The mean age was significantly younger in the subjects with longer education years. The frequency of female subjects decreased as the educational duration increased. Parental educational status was significantly associated with education status of the study participants; in subjects with educational duration ≤ 6 years, more than 90 % of parents were educated for ≤ 6 years, while only less than 1 % of parents were educated for > 12 years. In subjects with educational duration > 12 years, 27.7% of parents were educated for ≤ 6 years, whereas 23.1% of parents were educated for > 12 years, suggesting that the educational attainments of parents and their offspring are roughly proportionate. The ratio of urban residence significantly increased with the educational duration of individual subjects. Urinary sodium excretion (Na + /Cr) in random urine sample and estimated 24-h urine sodium was inversely related with subject's educational duration. SBP, DBP, waist circumference (WC) and body mass index (BMI) were also inversely correlated with subject's educational duration. Estimated glomerular filtration rate (eGFR) were more preserved in subjects with longer educational years, although no clear trend was observed between the prevalence of proteinuria and the subject's educational status. The prevalence of co-morbid conditions, such as HTN, diabetes mellitus (DM), dyslipidemia, coronary artery disease, stroke, anemia, and history of smoking, was significantly higher in subjects with lower educational status. Collectively, these suggests that the educational status of individuals is closely related with their medical conditions. Table 1. Baseline characteristics of study subjects by educational status. Values for categorical variables are given as number (percentage); values for continuous variables, as mean ± standard deviation. P value by oneway analysis of variance and χ 2 test for continuous and categorical variables, respectively. GFR, estimated glomerular filtration rate.  Table S2 online). DBP also peaked in subjects with education duration ≤ 6 years, except but in subgroups with age 60-80 years, where DBP peaked in subjects with educational duration 10-12 years. However, in subjects with age 19-39 years, the prevalence of HTN did not significantly differ by educational status, while in subjects with age 40-59 and age 60-80 years, prevalence of HTN were inversely correlated with educational status. To figure out whether educational status was independently associated with SBP and prevalent HTN, a series of regression models were analyzed. The analyses of entire subjects revealed that low educational status significantly increases SBP and prevalence of HTN, even after adjustment of co-variates (Supplementary Tables S3 and  S4 online). Similarly, in the analyses of subgroups stratified by age, low educational status was independently associated with increased SBP in all subgroups (Table 2). Conversely, the prevalence of HTN in subjects with age 19-39 years was not significantly associated with their educational status, even though low educational status independently increased the prevalence of HTN in subgroups with age 40-59 and 60-80 years. The analysis of a restricted cubic spline model with adjustment of co-variates demonstrated the overall impact of an individual's own educational status becomes more evident as the age increases ( Figure S2). Taken together, despite the robust association in general population, the impact of educational status on prevalent HTN differed across age subgroups, and was remarkably attenuated in young adults.
Parental educational status independently predicts prevalent HTN in young adults. Pursuing a socio-economic factor that predicts the risk of prevalent HTN in young adults, we focused on the role of parental educational status (Supplementary Table S5 online), as we hypothesized that the parental educational status might be critical for the socio-economic environment during childhood and juvenile periods of the subject, contributing to the formation of health behavior thereafter. In contrast to the educational status of study subjects, the educational status of parents significantly altered SBP, DBP, and prevalence of HTN in all age subgroups (Table 3). To validate independent associations of parental educational status with SBP and prevalent HTN, co-variates including the educational status of study subjects were adjusted in regression analyses, which revealed that low parental educational status was not independently associated either with SBP or with prevalent HTN (Supplementary Tables S6 and S7 online). Intriguingly, the association between low parental educational status and prevalent HTN was seen before adjustment with educational status of study subjects, but turned to be not significant after adjustment with the co-variate. As the impact of educational status on prevalent HTN differed across age subgroups (Table 2), the subgroups were analyzed to test age-specific impact of parental educational attainment on SBP or prevalent HTN (Table 4), where parental educational status was independently associated with both SBP and prevalent HTN in the subjects with age 19-39 years. Parental educational status was not independently associated with SBP in analyses of subjects with age 40-59 and age 60-80 years. The association of parental educational status and prevalent HTN was not significant in the analysis of subjects with age 40-59 years, and was only marginally significant (P = 0.049) in the analysis of subjects with age 60-80 years. To summarize, low parental educational status independently predicted elevated SBP and prevalent HTN specifically in young adults, although its association with SPB or prevalent HTN was much weaker in general popula- Low parental educational status is associated with high sodium intake in young adults. To unveil the mechanism linking the parental educational status and prevalent HTN in young adults, we compared urine sodium excretion of the subjects (Fig. 1), as evidences so far indicate an essential role of excess sodium intake in the development of HTN [5][6][7]18,19 . Na + /Cr in random urine and estimated 24-h urine sodium increased as the subject ages increase. Na + /Cr in random urine and estimated 24-h urine sodium significantly differ according to parental educational status in the subjects with age 19-39 years and, to a less degree, in the subjects with age 40-59 years, which finding was remarkably blunted in subjects with age 60-80 years. Although the association between low parental educational attainment and random urine Na + /Cr was significant before adjustment with educational status of study subjects, but was no more valid after adjustment with the co-variate in the regression analysis of the entire study subjects (Supplementary Table S8 online), while subgroup analyses demonstrated that parental educational status was independently associated with increased random urine Na + /  (Table 6). Therefore, these suggest that low parental educational status is associated with sodium intake in young adults, possibly contributing to the increased risk of HTN development.

Discussion
In the present study, we discovered that low parental educational status predicts prevalent HTN in young adults, but not in the middle-aged and elderly population. Although educational status of individual subjects is robustly associated with increases SBP and prevalence of HTN in general population, its impact on prevalent HTN differs across age subgroups, and is remarkably attenuated in young adults. Low parental educational status is also associated with high sodium intake in young adults, irrespective of subject's own educational status, possibly contributing to the increased risk of HTN development.
Of noticeable finding in this study is that the association between low parental attainment and HTN (Supplementary Table S7 online) or between low parental attainment and high dietary sodium intake (Supplementary Table 5. Impact of low parental educational status and SBP in various subgroups stratified by other than age. Models were adjusted for age, sex, co-morbidities (high body mass index, high waist circumference, diabetes, dyslipidemia, coronary artery disease, stroke, and history of smoking), estimated glomerular filtration rate, proteinuria, and educational status of individual subjects. BMI, body mass index; CI, confidence interval; CKD, chronic kidney disease; WC, waist circumference.   (Table 3) and dietary sodium intake (Table 4) was much clearly observed in the young adults, and was no more or only marginally valid in the subgroups with age > 40. These are in line with the previous studies of HTN in childhood and adolescent periods, where elevated BP was consistently associated with parental educational attainment 20-22 , but not with grandparental educational attainment 23,24 in this population, collectively suggesting that, as the age increases, the role of parental education status as a 'socio-economic legacy' fade away, and that the educational status of individual subjects emerges to dominantly determine lifestyle and health behavior. An observational study including 498 adolescent participants previously reported that the effect of parental education on BMI, lipid profiles, and SBP during young adulthood was statistically significant, but was no more significant after adjusting for participants' own education 25 . The result may seem slightly contradictory to our findings, since the cross-sectional analyses of more than 37,000 participants in the current study demonstrated that low educational attainment of parents is still a risk factor for high salt intake and HTN in young adults even after adjusting for educational status of individual study subjects. We, however, also observed that, with aging, the role of the individual's own educational status predominates in HTN prevalence and dietary sodium intake. (Tables 3 and 4). Therefore, findings both from the previous and current studies commonly emphasize that educated individuals would be less likely to develop HTN.
The mechanism how educational status is biologically transduced into HTN development is still elusive. A previous study indicated the BP in early life of the subjects with low parental educational attainment might track into adulthood 26 , while the rationale for elevated BP during childhood and adolescent period is lacking. Another study proved that the educational status of the young individual subjects overcomes the impact of parental educational attainment on BP 25 , although the biological explanation to link parental educational status and HTN development was not presented. In this regard, we hypothesized the contribution of sodium intake to HTN development in relation to educational status of individual subjects and their parents. Indeed, it has been believed that high sodium intake is closely linked to HTN development. Experimental evidences demonstrated that high dietary salt inhibits normal function of vascular endothelial cells to reduce nitric oxide synthesis and promote arterial stiffness 18 , leading to the elevation of BP. Cross sectional analysis of clinical data revealed that the excess amount of daily sodium intake is associated with poor BP control rate 19 . Most importantly, interventional studies to restrict dietary sodium intake alone or along with body weight reduction have proved the benefits in SBP and DBP control [5][6][7] . We demonstrated that random urine Na + /Cr is significantly associated with parental educational status specifically in young adults (Table 4), proving the hypothesis that high sodium intake of the young individuals with low parental educational status contributes to HTN development. Nevertheless, our results do not exclude the possible role of other factors in the development of HTN of individuals with low parental educational status, and the precise mechanism should be further clarified to more delicately guide the prevention of HTN in the vulnerable population.
In conclusion, we report that parental educational status, rather than individual's own educational status, better and independently predicts prevalent HTN in young adults, and that young adults with low parental educational status are prone to intake more sodium, possibly contributing to the increased risk of HTN development. Particular concerns are required for young hypertensive subjects, as the delivery optimal medical care is compounded in this population. We, therefore, expect that our findings could help define young individuals at risk of high sodium intake and HTN development.

Study design and participants. The Korea National Health and Nutrition Examination Survey
(KNHANES) is a nationwide population-based cross-sectional study of the health and nutritional status of the noninstitutionalized Korean population. It consists of a health questionnaire, physical/laboratory examinations, and nutrition survey. The present study analyzed data obtained from KNHANES 2008 to 2017 ( Figure S1 in Supplemental Data), because the measurement of urine sodium and creatinine has been included in the data since 2008. Written informed consent was obtained from each participant in KNHANES at the time of enroll- Table 6. Impact of low parental educational status on random urine Na + /Cr in the subgroups stratified by age. Model 1, unadjusted. Model 2, adjusted for age and sex. Model 3, model 2 + adjusted for co-morbidities (high body mass index, high waist circumference, diabetes, dyslipidemia, coronary artery disease, stroke, and history of smoking). Model 4, model 3 + adjusted for eGFR and proteinuria). Model 5, model 4 + adjusted for educational status of individual subjects. CI, confidence interval. Anthropometric and laboratory data. Trained medical staff performed physical examinations following standardized procedures. BP was measured manually 3 times at 30-s intervals after a minimum of 5 min of rest in a seated position and recorded as the average value of the 2nd and 3rd measurements. Blood samples were collected after at least an 8-h fast, properly processed, immediately refrigerated, and transported in cold storage to the central laboratory (Neodin Medical Institute, Seoul, Korea) within 24 h. eGFR was calculated from serum creatinine level using the CKD-Epidemiology Collaboration equation 27 . Urine sodium and creatinine concentration were determined in random urine specimen. Proteinuria was defined as albuminuria (≥ 1+) determined by dipstick urine test.
Demographic and clinical characteristics. Educational 32 , the ratio of sodium to creatinine (Na + /Cr) in random urine specimen was also calculated.
Statistical analysis. Data are presented as the mean ± standard deviation for continuous variables, and as number, or percent for categorical variables. To compare the difference in the baseline characteristics according to educational status of individuals and their parents, one-way analysis of variance and χ 2 test were used for continuous and categorical variables, respectively. The association between educational attainments of the subjects or their parents and BP, prevalence of HTN, or urinary sodium excretion was investigated by multivariate logistic regression methods adjusting for indicated variables in each table. A restricted cubic spline model with adjustment of indicated variables was analyzed to delineate the association between age and the risk of HTN by the individual subject's educational status. Statistical analyses were performed with SPSS (version 20.0; SPSS Inc). P < 0.05 was considered statistically significant. www.nature.com/scientificreports/ Publisher's note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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