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Individual and combined association analysis of famine exposure and serum uric acid with hypertension in the mid-aged and older adult: a population-based cross-sectional study

Abstract

Background

Malnutrition in early life may affect health in later life. The associations between malnutrition and serum uric acid (SUA) and hypertension were inconsistent. The present study aimed to investigate the individual and combined association between famine exposure and serum uric acid and hypertension in middle-aged and older Chinese.

Methods

Data were selected from the China Health and Retirement Longitudinal Study (CHARLS) Wave2011. The analytic sample included 9368 individuals aged 45 to 90. Differences between baseline characteristics and famine exposure/SUA level were evaluated using the Chi-square test, t-test, and F-test. Then, the differences in the prevalence of hypertension between characteristic groups was also estimated by the Chi-square and t-test. Finally, multivariable-adjusted logistic regression models examined association of famine exposure and serum uric acid with odds of prevalence of hypertension.

Results

A total of 9368 individuals were enrolled in the study, 4366 (46.61%) and 5002 (53.39%) were male and female, respectively. Among males, 459 (10.51%) had been exposed to the Chinese famine during the fetal stage, whereas 1760 (40.31%) and 1645 (37.68%) had been exposed to the famine during childhood and adolescence/adult stage, respectively. Among females, 635 (12.69%) had been exposed to the Chinese famine during the fetal stage, whereas 1988 (39.74%) and 1569 (31.37%) had been exposed to the famine during childhood and adolescence/adult stage, respectively. Regarding the participants with SUA level measurements, 290 (6.64%) reported having Hyperuricemia (HUA) in males and 234 (4.68%) in the females. Furthermore, 1357 (31.08%) reported having hypertension in male and 1619 (32.37%) in the female. In multivariable-adjusted model, famine exposure and serum uric acid were associated with prevalence of hypertension independently in total populations [(1) Model fourd, fatal exposed group vs non-exposed group: 1.25 (95% CI 1.03, 1.52); childhood-exposed group vs non-exposed group:1.60 (95% CI 1.37, 1.87); adolescence/adult exposed group vs non-exposed group: 2.87 (95% CI 2.44, 3.37), P for trend < 0.001; (2) Model four e, high vs normal:1.73 (95% CI 1.44, 2.08)]. When stratified by sex, the results in both males and females were similar to those in the total population. In general, interaction analysis in the multivariable-adjusted model, compared with the combination of normal SUA level and no-exposed famine stage, all groups trended towards higher odds of prevalence of hypertension [the greatest increase in odds, adolescence/adult exposed stage and high SUA level in total participants: OR4.34; 95%CI 3.24, 5.81; P for interaction < 0.001]. When stratified by sex, the results in both males and females were also similar to those in the total population.

Conclusion

Our data support a strongly positive individual and combined association of famine exposure and serum uric acid with hypertension in middle-aged and elderly Chinese.

Peer Review reports

Background

Hypertension is a severe medical condition that significantly increases cardiovascular disease as well as other chronic diseases [1,2,3]. Hypertension risk factors [4,5,6,7,8] include stress, harmful use of alcohol, salt consumption, low intake of fruits and vegetables, being overweight or obese, saturated fat and trans fats, tobacco use, low diet in vitamin D, lack of physical activity, family history, aged 65 years or over and co-existing diseases. Though the etiology of hypertension is complex, it was known as one of the risk factors was high serum uric acid (SUA). Most mechanisms [9] supported that uric acid (UA) induced acute vasoconstriction by activation of renin-angiotensin system (RAS), followed by uric acid uptake into vascular smooth muscle cells leading to cellular proliferation and secondary arteriolosclerosis that results in chronic salt-sensitive hypertension. Thus, increased serum uric acid increases the risk of developing hypertension. In addition to known and probable risk factors for hypertension, early life mal-nutrition may also affect hypertension. Though the mechanisms are unclear, it is speculated that some fetal growth regulation factors might be most vulnerable to nutrient deficiencies, specifically during fetal and early postnatal life, dependent on the window of exposure [10].

It was hypothesized that early developmental adaptions in response to malnutrition in early life, which are key determinants of short-term survival, have adverse cardiovascular outcomes [11, 12]. Historical famine exposure has provided a unique and natural opportunity to test the hypothesis. Previous famine studies [10, 13,14,15,16,17,18,19,20,21,22,23,24] have provided pieces of evidence to support the association between famine exposure and increased risk of hypertension. Most studies [10, 13, 15, 17,18,19,20,21,22,23,24] found that exposure to famine in early life increases the risk of BP/hypertension in adulthood. Furthermore, exposure to famine has more deleterious effects on adult health for women than men [14, 16]. However, other studies [15, 25, 26] did not find a significant association between famine exposure and hypertension. Therefore, the association between famine exposure in early life and the risk of BP/hypertension in later life needs to be further studied. Moreover, results also indicated the malnutrition in early life were more strongly correlated with hyperuricemia in late life [27, 28]. It is not completed understood association and interaction analysis between famine exposure and serum uric acid and hypertension in the mid-age and older adult.

Given the limitations of previous studies, our research analyzed data from the China Health and Retirement Longitudinal Study (CHARLS) Wave1 and aimed to investigate the individual and combined association between famine exposure and serum uric acid and hypertension after adjustment for confounding variables.

Methods

Study design and setting

Data selected from the China Health and Retirement Longitudinal Study (CHARLS) Wave1 were analyzed in our research. The CHARLS is an ongoing nationally representative longitudinal study of middle-aged and elderly individuals in China that is conducted by the China Centre for Economic Research at Peking University [29] from 2011. In the 2011 CHARLS Wave1, at baseline, 17,707 individuals were recruited in the first visit. We selected individuals aged 45 years and older. After excluding participants who had missing values of the baseline characteristics and measurements, 9368 were included in our research. All data are openly published as microdata at http://charls.pku.edu.cn/index/zh-cn.html with no direct contact with all participants.

Individuals

The individuals of the study were selected from the China Health and Retirement Longitudinal Study (CHARLS), Wave 1 (2011) [29]. The age of CHARLS involved 9368 individuals were [mean ± standard deviation age = 59.47 ± 9.31 years, and ranged from 45 to 90 years]. The mean and standard deviation of age were 60.23 ± 9.22 years (ranged from 45 to 90 years) in males and 58.80 ± 9.33 years (ranged from 45 to 90 years) in females.

Baseline characteristics

Baseline variables including age, sex, education, marital status, living place, smoking status, alcohol consumption status, eating meals, social and leisure activities, the experience of a traumatic event, physical exercise habit were collected using a type of self-report method. Sex was categorized as male and female. Education was divided into four groups: illiterate, less than elementary school, high school, and above vocational school. Marital status was categorized into single and married. The living place was classed as rural and urban. Smoking status was defined as never smoker, former smoker, and current smoker. Alcohol consumption status was classed as no drinking, less than once a month, and more than once a month. Eating habit was divided into three groups: ≤ 2 meals per day, 3 meals per day, and ≥ 4 meals per day. Social and leisure activities, the experience of a traumatic event was categorized into “yes” and “no”. Physical exercise habit was defined as no exercise, less than regular physical exercises, and regular physical exercises. All variables were depending on our previous research studies [30,31,32,33,34,35].

Measurements

Body measure index (BMI) was calculated based on the measured weight and height of the participants. Hypertension was defined as systolic blood pressure (SBP) of ≥ 140 mmHg and/or diastolic blood pressure (DBP) of ≥ 90 mmHg, the definition has been widely used in our previous studies[30, 32, 34, 35]. SUA was measured by the enzymatic colormetric test in the Youanmen Center for Clinical Laboratory at Capital Medical University. Hyperuricemia (HUA) was defined as SUA concentration of > 6 mg/dL in females and > 7 mg/dL in males [36].

Exposure age and exposed stages

The famine period was between 1959 and 1962, famine exposure is set up on the birth year. Like the previous Chinese famine study [37], participants were categorized into four exposure groups: no-exposed stage (born between 1963-01-01 and 1966-12-31), fetal exposed stage (born between 1959-01-01 and 1962-12-31), childhood exposed stage (born between 1949-01-01 and 1958-12-31), adolescence/adult exposed stage (born between1921-01-01 and 1948-12-31).

Statistical analysis

The data are presented as means and standard deviation (SD) unless indicated otherwise. Means and standard deviation (continuous data) were used to describe continuous variables (age, BMI), and number and percentage (categorical data) were used to assess the categorical variables (sex, education, marital status, living place, alcohol consumption status, smoking status, eating meals, social and leisure activities, the experience of a traumatic event, taking physical activity or exercise, SUA levels, famine exposure and hypertension categories). Differences between baseline characteristics (education, marital status, living place, social and leisure activities, the experience of a traumatic event, taking physical activity or exercise, hypertension) and categories of famine exposure stages/SUA levels were also evaluated using the chi-square test (categorical data). Between-group differences according to hypertension (hypertension, no-hypertension) were evaluated by the chi-square test (categorical data). Age and BMI between groups were used by t-test or F-test. For our research, logistic regression models were conducted to assess odds ratios (ORs) with accompanying 95% confidence intervals (95% CIs) as estimates of associations of SUA levels and exposure stages separately and in combination, with the prevalence of hypertension. Furthermore, the logistic regression models were employed to explore the linear trend P-value in subgroups. Famine exposure-SUA interaction analysis was examined by introducing the interaction term [famine exposure × SUA] into the confounder-adjusted logistic regression models. All statistical analyses were performed with SPSS software, version 25.0 (IBM SPSS, Armonk, NY, USA), and P < 5% was considered as a significant level.

Results

Table 1 shows the basic characteristics of participants. A total of 9368 individuals were enrolled in the study, 4366 (46.61%) and 5002 (53.39%) were male and female, respectively. Among males, 459 (10.51%) had been exposed to the Chinese famine during the fetal stage, whereas 1760 (40.31%) and 1645 (37.68%) had been exposed to the famine during childhood and adolescence/adult stage, respectively. The distribution of physical exercises habit did not demonstrate a significantly statistical difference among the four birth groups. On the other hand, the differences were observed in the distribution of age, BMI, education, marital status, living place, cigarette smoking, alcohol consumption status, eating habit, social events, history of accidental injury, hypertension, and SUA levels. Among females, 635 (12.69%) had been exposed to the Chinese famine during the fetal stage, whereas 1988 (39.74%) and 1569 (31.37%) had been exposed to the famine during childhood and adolescence/adult stage, respectively. Furthermore, the distribution of living place and history of accidental injury did not demonstrate significantly statistical differences among the four birth groups. On the other hand, the difference was observed in the distribution of age, BMI, education, marital status, cigarette smoking, alcohol consumption status, eating habit, social events, physical exercises habit, hypertension, and SUA levels.

Table 1 Characteristics of participants in the cohort study by level of famine exposure (N = 9368)

Table 2 shows the characteristics of study participants categorized by SUA levels. Of the participants, 290 (6.64%) reported having HUA in the male and 234 (4.68%) in the female. In males, significant differences were observed in age, BMI, living place, cigarette smoking, alcohol consumption status, physical exercises habit, famine exposed stages, and hypertension groups (P < 0.05) between participants with and without HUA. Regarding the females, significant differences were observed in age, BMI, marital status, living place, cigarette smoking, famine exposed stages, and hypertension groups (P < 0.05) between participants with and without HUA.

Table 2 Characteristics of participants in the cohort study by level of SUA levels (N = 9368)

Table 3 shows the characteristics of study participants categorized by blood pressure status. Of the participants, 1357 (31.08%) reported having hypertension in male and 1619 (32.37%) in the female. In males, significant differences were observed in age, BMI, education, marital status, living place, history of accidental injury, famine stages, and hypertension groups (P < 0.05) between participants with and without hypertension. In females, significant differences in distribution were observed between blood pressure status in the variables, including age, BMI, education, marital status, alcohol consumption status, famine stages, and SUA level groups.

Table 3 Characteristics of study participants of cross-sectional study categorized by blood pressure status (N = 9368)

Table 4 shows the separate associations of famine exposure, SUA levels with the prevalence of hypertension. Firstly, after controlling for confounding factors including age, education, marital status, living place, smoking status, alcohol consumption status, eating meals, social and leisure activities, the experience of a traumatic event, taking physical activity or exercise, BMI, and famine exposure in a multivariable logistic regression model four, higher odds of prevalence of hypertension in the total population were observed with increasing levels of SUA [high vs normal:1.73 (95% CI 1.44, 2.08) independently of famine stages only. When stratified by sex, the results of model four in both males and females were similar to those in the total population. Secondly, after controlling for confounding factors including age, education, marital status, living place, smoking status, alcohol consumption status, eating meals, social and leisure activities, the experience of a traumatic event, taking physical activity or exercise, BMI, and SUA levels in a multivariable logistic regression model four, higher odds of prevalence of hypertension in the total population were observed with famine exposed stages [fatal exposed group vs non-exposed group: 1.25 (95% CI 1.03, 1.52); childhood-exposed group vs non-exposed group:1.60 (95% CI 1.37, 1.87); adolescence/adult exposed group vs non-exposed group: 2.87 (95% CI 2.44, 3.37), P for trend < 0.001] independently of SUA levels only. When stratified by sex, the results of model four in both males and females were similar to those in the total population.

Table 4 Separate associations of famine exposure, SUA levels with prevalence of hypertension (N = 9368)

Table 5 shows the combined associations of SUA levels and famine exposure with the prevalence of hypertension. Compared with the combination of normal SUA level and no-exposed famine stage, all groups trended towards higher odds of prevalence of hypertension; Furthermore, in multivariable model one, the greatest increase in odds was observed for the adolescence/adult exposed stage and high SUA level combination (adolescence/adult exposed stage and HUA in total participants: OR 4.37; 95%CI 3.28,5.81). And similarly, in multivariable-adjusted model two, the highest odds of prevalence of hypertension were observed for the adolescence/adult exposed stage and HUA combination (adolescence/adult exposed stage and high SUA in total participants: OR 3.94; 95%CI 2.96, 5.26). Additionally, in multivariable-adjusted model three, the highest odds of prevalence of hypertension were observed for the adolescence/adult exposed stage and high SUA combination (adolescence/adult exposed stage and HUA in total participants: OR3.99; 95%CI 2.99, 5.32). In multivariable-adjusted model four, the highest odds of prevalence of hypertension were observed for the adolescence/adult exposed stage and HUA combination (adolescence/adult exposed stage and high SUA level in total participants: OR4.34; 95%CI 3.24, 5.81). Finally, combined associations of high SUA levels and famine exposure with the prevalence of hypertension were observed in the total participant (P-interaction < 0.001). When stratified by sex, the results of the model in both males and females were similar to those in the total population.

Table 5 Combined associations of SUA levels and famine exposure with prevalence of hypertension (N = 9368)

Discussion

Our research aimed to explore the individual and combined association between famine exposure and serum uric acid and hypertension in mid-aged and older adults. Interestingly, our study found that the individuals exposed to famine in early life had an increased risk of hypertension in adult. After adjustment for observed confounders, including age, education, marital status, living place, smoking status, alcohol consumption status, eating meals, social and leisure activities, the experience of a traumatic event, taking physical activity or exercise, BMI, and SUA level, the associations still existed both in males and females. Additionally, the study showed that there were linear trends in the associations of SUA with hypertension. After adjustment for observed confounders, including age, education, marital status, living place, smoking status, alcohol consumption status, eating meals, social and leisure activities, the experience of a traumatic event, taking physical activity or exercise, BMI, and famine exposure, the associations still existed both in males and females. In general, our data support a strongly positive individual and combined association of famine exposure and SUA levels with hypertension in middle-aged and elderly Chinese. The outcomes of these individuals stratified by sex were examined. The results in both males and females were also similar to those in the total population.

The Chinese famine ranged from the late1950s to the early 1960s, caused over 30 million excess deaths in most areas [38]. Most studies have reported the associations of famine exposure during early life with hypertension in adults, but no consistent associations were observed. Therefore, this research attempted to examine the individual and combined association between famine exposure and serum uric acid and hypertension based on a population-based cross-sectional study from CHARLS. Our data support a strongly positive combined association of famine exposure and serum uric acid with hypertension in middle-aged and elderly Chinese. Both nutrition intervention for exposure to the famine in early life and serum uric acid reduction in later life may be required to substantially reduce the prevalence of hypertension.

As the worst famine, the survivors might be healthier than the weak members were kicked out, a common finding that is in line with Darwin’ s theory of survival of the fittest [39]. In this case, the participants exposed to famine in early life should decrease the risk of hypertension in adults. This was not observed in our research. When facing the later “rich” environment, the risk of hypertension may be increased. The outcomes are partly in line with previous studies. Although the Dutch famine and the Leningrad siege study [40,41,42] found that early-life exposure to famine was not associated with hypertension, most studies [10, 13, 14, 16,17,18,19,20,21,22,23,24] in China indicated that exposure to famine in early life increased the risk of hypertension. However, this association did not exist between the Chinese famine and hypertension risk in Chongqing [25]. Such discrepancies between those studies may be a result of methodological differences in definitions of famine exposure groups and the different sample selection effect. Additionally, these studies have been criticized for not being adjusted the effect of age. To control the potential age confounding, we categorized the famine exposure into four exposure groups [no-exposed stage (born between1963 and 1966), fetal exposed stage (born between1959 and 1962), childhood exposed stage (born between 1949 and 1958), adolescence/adult exposed stage (born between1921 and 1948)] based on the birth year and we also combined the no-exposure as the reference group to identify the effect of the fetal exposed stage, childhood exposed stage, adolescence/adult exposed stage. Our results suggested that early famine exposure was associated with an increased risk of hypertension. The sex difference of early life famine exposure and hypertension were common in several studies [16, 18]. Furthermore, exposure to famine during early life exerted more deleterious association on women than men. This could be explained by the fact the women may suffer more than men during the famine because of the dominance of a patriarchal mentality in China [43]. The main potential mechanisms of the relationship between famine exposure in early life and the increased risk of hypertension in later life were still not fully understood. Animal models [44, 45] have proved that undernutrition in early life could lead to hypertension in later life. In addition, epigenetic might play a part role in the relationship between famine exposure in early life and hypertension in adults [46, 47]. Though the potential mechanisms are unclear, it is speculated that some fetal growth regulation factors might be most vulnerable to nutrient deficiencies, specifically during fetal and early postnatal life, dependent on the window of exposure [10].

Although previous studies [48,49,50,51,52,53,54,55] have estimated the association between serum uric acid level and blood pressure/hypertension. However, the results are not consistent. Y. Kansui, T. Ohtsubo, K. Goto, et al.[48]found that both systolic and diastolic blood pressures were significantly correlated with serum uric acid among Japanese male workers aged 18–64 years. Lyngdoh et al. [49] found that adiposity substantially decreased the association between SUA and BP in adults, and BP was independently associated with SUA in females. Kawamoto et al. [50] found that serum uric acid level significantly associated with both systolic blood pressure (SBP) and diastolic blood pressure (DBP) in females aged < 55 years but not in those aged ≥ 55 years. Irijanto et al. [53]found that community-dwelling Japanese men with a BMI ≥ 21.0 kg/m2, serum uric acid level was positively correlated with SBP and DBP, but negatively associated with SBP and DBP in those with a BMI of ≥ 21.0 kg/m2. Lin et al. [55] found that serum UA levels are significantly correlated to BP in Taiwanese adolescents aged 14–19 years. Khanum et al. [56] found that the relationship between elevated SUA level and incident hypertension was observed among individuals aged < 55 years, but not observed among participants aged ≥ 55 years. Cao et al. [57] found that the positive relationship between elevated SUA level and hypertension was proved in a Chinese population. Several longitudinal studies [58,59,60,61] found that the serum uric acid level was positively related with the risk of incident hypertension independently. Similarly, other cross-sectional [62,63,64] also found that hyperuricemia was significantly related with the risk of hypertension. The difference between those studies may due to the different confounding variables by controlling, the different populations, and different sampling methods selection. Several hypotheses partly explain the association between SUA level and high blood pressure/hypertension. One of the possible mechanism might be uric acid deposition on the blood vessels walls activates the renin-angiotensin system, suppress the liberate of carbon monoxide, enhance inflammation, and leads to vasoconstriction later [62]. Another possibility involving oxidative stress and endothelial dysfunction related with high SUA level may contribute to elevated blood pressure [65, 66].

There were so many studies that had explored the association analysis between famine exposure/ obesity parameters and BP/hypertension, and only two studies that explored the combined association between famine exposure and obesity parameters and hypertension, but no study was aimed to investigate the combined association of famine exposure and serum uric acid with hypertension after adjustment for confounding variables. Yu et al.[20] found that interactions between famine and obesity on hypertension prevalence risk were not observed. In contrast, Li et al. [13] reported that a stronger interaction between obesity and famine exposure concerning BP among individuals who were exposed to famine during fetal life and had a western dietary pattern in adults was observed. Two studies [27, 28] also found famine exposure was associated with an increased risk of hyperuricemia in adulthood. Interestingly, our data support a strongly positive combined association of famine exposure and serum uric acid with hypertension in middle-aged and elderly Chinese.

There were several limitations to the study. First, selection bias was to be considered: famine may weed out the frail members of the population and leave the healthier ones. Second, famine exposure for each individual was unknown. Third, not all families were equally affected by famine exposure. Fourth, the data was collected in 2011, and more recent studies are needed to identify the associations. However, the results provided large data that could be explored further in the combined association of famine exposure and serum uric acid with hypertension. Moreover, a significant strength of the study is the large sample of 9368 middle-aged and older Chinese. Another strength is the analytical method the controlled the potential confounders.

Conclusions

Our data support a positive individual and combined association of famine exposure and serum uric acid with hypertension in middle-aged and elderly Chinese. Both nutrition intervention for exposure to the famine in early life and serum uric acid reduction in later life may be required to substantially reduce the risk of hypertension.

Availability of data and materials

The datasets generated and/or analyzed during the current study are publicly available in the http://charls.pku.edu.cn/index.html repository.

Abbreviations

BMI:

Body mass index

CHARLS:

China Health and Retirement Longitudinal Study

CI:

Confidence interval

DBP:

Diastolic blood pressure

NSFC:

The National Natural Science Foundation of China

UA:

Uric acid

RAS:

Renin-angiotensin system

SD:

Standard deviation

NIA:

National Institute on Aging

OR:

Odds ratios

SUA:

Serum uric acid

HUA:

High serum uric acid

UA:

Uric acid

SBP:

Systolic blood pressure

References

  1. de Kouchkovsky I, Mayfield J, Kohlwes J. Hypertension in young adults and subsequent cardiovascular disease. JAMA. 2019;321(13):1310.

    Article  PubMed  Google Scholar 

  2. Gutierrez J, Alloubani A, Mari M, Alzaatreh M. Cardiovascular disease risk factors: hypertension, diabetes mellitus and obesity among Tabuk citizens in Saudi Arabia. Open Cardiovasc Med J. 2018;12:41–9.

    Article  PubMed  PubMed Central  Google Scholar 

  3. James JE. Hypertension control and cardiovascular disease. Lancet. 2017;389(10065):154.

    Article  PubMed  Google Scholar 

  4. Abdulsalam S, Olugbenga-Bello A, Olarewaju O, Abdus-Salam I. Sociodemographic correlates of modifiable risk factors for hypertension in a rural local government area of oyo state South west Nigeria. Int J Hypertens. 2014;2014:842028.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Ke L, Ho J, Feng J, Mpofu E, Dibley MJ, Feng X, Van F, Leong S, Lau W, Lueng P, et al. Modifiable risk factors including sunlight exposure and fish consumption are associated with risk of hypertension in a large representative population from Macau. J Steroid Biochem Mol Biol. 2014;144(Pt A):152–5.

    Article  CAS  PubMed  Google Scholar 

  6. Ibekwe R. Modifiable risk factors of hypertension and socio-demographic profile in Oghara, Delta State; prevalence and correlates. Ann Med Health Sci Res. 2015;5(1):71–7.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Pilakkadavath Z, Shaffi M. Modifiable risk factors of hypertension: a hospital-based case-control study from Kerala, India. J Family Med Prim Care. 2016;5(1):114–9.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Mamudu HM, Paul TK, Wang L, Veeranki SP, Panchal HB, Alamian A, Budoff M. Association between multiple modifiable risk factors of cardiovascular disease and hypertension among asymptomatic patients in central appalachia. South Med J. 2017;110(2):90–6.

    Article  PubMed  Google Scholar 

  9. Feig DI. Hyperuricemia and hypertension. Adv Chronic Kidney Dis. 2012;19(6):377–85.

    Article  PubMed  Google Scholar 

  10. Wang PX, Wang JJ, Lei YX, Xiao L, Luo ZC. Impact of fetal and infant exposure to the Chinese Great Famine on the risk of hypertension in adulthood. PLoS ONE. 2012;7(11):e49720.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Gluckman PD, Hanson MA, Cooper C, Thornburg KL. Effect of in utero and early-life conditions on adult health and disease. N Engl J Med. 2008;359(1):61–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Alexander BT. Fetal programming of hypertension. Am J Physiol Regul Integr Comp Physiol. 2006;290(1):R1–10.

    Article  CAS  PubMed  Google Scholar 

  13. Li Y, Jaddoe VW, Qi L, He Y, Lai J, Wang J, Zhang J, Hu Y, Ding EL, Yang X, et al. Exposure to the Chinese famine in early life and the risk of hypertension in adulthood. J Hypertens. 2011;29(6):1085–92.

    Article  CAS  PubMed  Google Scholar 

  14. van Abeelen AFM, de Rooij SR, Osmond C, Painter RC, Veenendaal MVE, Bossuyt PMM, Elias SG, Grobbee DE, van der Schouw YT, Barker DJP, et al. The sex-specific effects of famine on the association between placental size and later hypertension. Placenta. 2011;32(9):694–8.

    Article  PubMed  Google Scholar 

  15. Carroll D, Ginty AT, Painter RC, Roseboom TJ, Phillips AC, de Rooij SR. Systolic blood pressure reactions to acute stress are associated with future hypertension status in the Dutch Famine Birth Cohort Study. Int J Psychophysiol. 2012;85(2):270–3.

    Article  PubMed  Google Scholar 

  16. Chen H, Nembhard WN, Stockwell HG. Sex-specific effects of fetal exposure to the 1959–1961 Chinese famine on risk of adult hypertension. Matern Child Health J. 2014;18(3):527–33.

    Article  PubMed  Google Scholar 

  17. Wang Z, Li C, Yang Z, Zou Z, Ma J. Infant exposure to Chinese famine increased the risk of hypertension in adulthood: results from the China Health and Retirement Longitudinal Study. BMC Public Health. 2016;16:435.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Liu L, Xu X, Zeng H, Zhang Y, Shi Z, Zhang F, Cao X, Xie YJ, Reis C, Zhao Y. Increase in the prevalence of hypertension among adults exposed to the Great Chinese Famine during early life. Environ Health Prev Med. 2017;22(1):64.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Wu L, Feng X, He A, Ding Y, Zhou X, Xu Z. Prenatal exposure to the Great Chinese Famine and mid-age hypertension. PLoS ONE. 2017;12(5):e0176413.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Yu C, Wang J, Li Y, Han X, Hu H, Wang F, Yuan J, Yao P, Miao X, Wei S, et al. Exposure to the Chinese famine in early life and hypertension prevalence risk in adults. PLoS ONE. 2017;35(1):63–8.

    CAS  Google Scholar 

  21. Liu L, Xu X, Zeng H, Zhang Y, Shi Z, Zhang F, Cao X, Xie YJ, Reis C, Zhao Y. Correction to: Increase in the prevalence of hypertension among adults exposed to the great Chinese famine during early life. Environ Health Prev Med. 2018;23(1):11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Shi Z, Nicholls SJ, Taylor AW, Magliano DJ, Appleton S, Zimmet P. Early life exposure to Chinese famine modifies the association between hypertension and cardiovascular disease. J Hypertens. 2018;36(1):54–60.

    Article  CAS  PubMed  Google Scholar 

  23. Xin X, Yao J, Yang F, Zhang D. Famine exposure during early life and risk of hypertension in adulthood: a meta-analysis. Crit Rev Food Sci Nutr. 2018;58(14):2306–13.

    Article  PubMed  Google Scholar 

  24. Zhao R, Duan X, Wu Y, Zhang Q, Chen Y. Association of exposure to Chinese famine in early life with the incidence of hypertension in adulthood: a 22-year cohort study. Nutr Metab Cardiovasc Dis. 2019;29(11):1237–44.

    Article  PubMed  Google Scholar 

  25. Chen JP, Peng B, Tang L, Sun R, Hu S, Wen XY, Que P, Wang YH. Fetal and infant exposure to the Chinese famine increases the risk of fatty liver disease in Chongqing, China. J Gastroenterol Hepatol. 2016;31(1):200–5.

    Article  PubMed  Google Scholar 

  26. Zhou J, Sheng J, Fan Y, Zhu X, Tao Q, Liu K, Hu C, Ruan L, Yang L, Tao F, et al. The effect of Chinese famine exposure in early life on dietary patterns and chronic diseases of adults. Public Health Nutr 2018;1–11

  27. Wang Y, Weng P, Wan H, Zhang W, Chen C, Chen Y, Cai Y, Guo M, Xia F, Wang N, et al. Economic status moderates the association between early-life famine exposure and hyperuricemia in adulthood. J Clin Endocrinol Metab. 2020;105(11):dgaa523.

    Article  PubMed  Google Scholar 

  28. Zhang W, Luan R. Early-life exposure to the Chinese famine of 1959–61 and risk of Hyperuricemia: results from the China health and retirement longitudinal study. BMC Public Health. 2020;20(1):15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Li C, Liu T, Sun W, Wu L, Zou ZY. Prevalence and risk factors of arthritis in a middle-aged and older Chinese population: the China health and retirement longitudinal study. Rheumatology. 2015;54(4):697–706.

    Article  PubMed  Google Scholar 

  30. Zhang L, Liu K, Li H, Li D, Chen Z, Zhang LL, Guo LL. Relationship between body mass index and depressive symptoms: the “fat and jolly” hypothesis for the middle-aged and elderly in China. BMC Public Health. 2016;16(1):1201.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Zhang L, Li JL, Zhang LL, Guo LL, Li H, Li D. No association between C-reactive protein and depressive symptoms among the middle-aged and elderly in China Evidence from the China Health and Retirement Longitudinal Study. Medicine. 2018;97(38):e12352.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Zhang L, Li JL, Zhang LL, Guo LL, Li H, Li D. Association and interaction analysis of body mass index and triglycerides level with blood pressure in elderly individuals in China. Biomed Res Int. 2018;2018:8934534.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Zhang L, Li JL, Zhang LL, Guo LL, Li H, Yan WZ, Li D. Relationship between adiposity parameters and cognition: the “fat and jolly” hypothesis in middle-aged and elderly people in China. Medicine. 2019;98(10):e14747.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Zhang L, Li JL, Zhang LL, Guo LL, Li H, Li D. Body mass index and serum uric acid level: Individual and combined effects on blood pressure in middle-aged and older individuals in China. Medicine. 2020;99(9):e19418.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Zhang L, Li JL, Guo LL, Li H, Li D, Xu G. The interaction between serum uric acid and triglycerides level on blood pressure in middle-aged and elderly individuals in China: result from a large national cohort study. BMC Cardiovasc Disord. 2020;20(1):174.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Teng F, Zhu R, Zou C, Xue Y, Yang M, Song H, Liang J. Interaction between serum uric acid and triglycerides in relation to blood pressure. J Hum Hypertens. 2011;25(11):686–91.

    Article  CAS  PubMed  Google Scholar 

  37. Wang N, Wang X, Li Q, Han B, Chen Y, Zhu C, Chen Y, Lin D, Wang B, Jensen MD, et al. The famine exposure in early life and metabolic syndrome in adulthood. Clin Nutr. 2017;36(1):253–9.

    Article  PubMed  Google Scholar 

  38. Li Y, Zhao L, Yu D, Ding G. Exposure to the Chinese famine in early life and depression in adulthood. Psychol Health Med. 2018;23(8):952–7.

    Article  CAS  PubMed  Google Scholar 

  39. Song S. Does famine have a long-term effect on cohort mortality? Evidence from the 1959–1961 great leap forward famine in China. J Biosoc Sci. 2009;41(4):469–91.

    Article  PubMed  Google Scholar 

  40. de Rooij SR, Painter RC, Holleman F, Bossuyt PM, Roseboom TJ. The metabolic syndrome in adults prenatally exposed to the Dutch famine. Am J Clin Nutr. 2007;86(4):1219–24.

    Article  PubMed  Google Scholar 

  41. Stein AD, Zybert PA, van der Pal-de BK, Lumey LH. Exposure to famine during gestation, size at birth, and blood pressure at age 59 y: evidence from the Dutch Famine. Eur J Epidemiol. 2006;21(10):759–65.

    Article  PubMed  Google Scholar 

  42. Stanner SA, Bulmer K, Andrès C, Lantseva OE, Borodina V, Poteen VV, Yudkin JS. Does malnutrition in utero determine diabetes and coronary heart disease in adulthood? Results from the Leningrad siege study, a cross sectional study. BMJ (Clinical research ed). 1997;315(7119):1342–8.

    Article  CAS  Google Scholar 

  43. Khanal P, Johnsen L, Axel AM, Hansen PW, Kongsted AH, Lyckegaard NB, Nielsen MO. Long-term impacts of foetal malnutrition followed by early postnatal obesity on fat distribution pattern and metabolic adaptability in adult sheep. PLoS ONE. 2016;11(6):e0156700.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Bol V, Desjardins F, Reusens B, Balligand JL, Remacle C. Does early mismatched nutrition predispose to hypertension and atherosclerosis, in male mice? PLoS ONE. 2010;5(9):e12656.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  45. Bai SY, Briggs DI, Vickers MH. Increased systolic blood pressure in rat offspring following a maternal low-protein diet is normalized by maternal dietary choline supplementation. J Dev Orig Health Dis. 2012;3(5):342–9.

    Article  CAS  PubMed  Google Scholar 

  46. Kubaszek A, Markkanen A, Eriksson JG, Forsen T, Osmond C, Barker DJ, Laakso M. The association of the K121Q polymorphism of the plasma cell glycoprotein-1 gene with type 2 diabetes and hypertension depends on size at birth. J Clin Endocrinol Metab. 2004;89(5):2044–7.

    Article  CAS  PubMed  Google Scholar 

  47. Aagaard-Tillery KM, Grove K, Bishop J, Ke X, Fu Q, McKnight R, Lane RH. Developmental origins of disease and determinants of chromatin structure: maternal diet modifies the primate fetal epigenome. J Mol Endocrinol. 2008;41(2):91–102.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Kansui Y, Ohtsubo T, Goto K, Sakata S, Ichishima K, Fukuhara M, Ohta Y, Matsumura K. Association of serum uric acid with blood pressure in Japanese men Cross-sectional study in work-site group. Circ J. 2011;75(12):2827–32.

    Article  CAS  PubMed  Google Scholar 

  49. Lyngdoh T, Viswanathan B, Myers GJ, Bochud M, Bovet P. Impact of different adiposity measures on the relation between serum uric acid and blood pressure in young adults. J Hum Hypertens. 2012;26(11):677–83.

    Article  CAS  PubMed  Google Scholar 

  50. Kawamoto R, Tabara Y, Kohara K, Kusunoki T, Abe M, Miki T. Synergistic influence of age and serum uric acid on blood pressure among community-dwelling Japanese women. J Clin Hypertens (Greenwich). 2013;36(7):634–8.

    CAS  Google Scholar 

  51. Kawamoto R, Ninomiya D, Senzaki K, Kumagi T. Interaction between body mass index and serum uric acid in relation to blood pressure in community-dwelling Japanese men. Clin Hypertens. 2018;24:1.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Ninomiya D, Senzaki K, Kumagi T, Kawada T. Relationship between serum uric acid and blood pressure by adjusting dietary factors. Clin Hypertens. 2018;20(2):418.

    Article  Google Scholar 

  53. Irijanto F, Zulaela Z, Widiatmoko A, Kholiq A, Tomino Y, Kawamoto R. Interaction between body mass index and serum uric acid in relation to blood pressure in community-dwelling Japanese men. BMJ Open. 2018;24:1.

    Google Scholar 

  54. Yang CC, Bawazier LA, Sjabani M. Association of serum uric acid, morning home blood pressure and cardiovascular risk factors in a population with previous prehypertension: a cross-sectional study. Blood Press. 2020;10(9):e038046.

    Google Scholar 

  55. Lin KH, Yen FS, Chen HS, Hwu CM. Serum uric acid and blood pressure among adolescents: data from the Nutrition and Health Survey in Taiwan (NAHSIT) 2010–2011. Blood Press. 2021;30(2):118–25.

    Article  PubMed  Google Scholar 

  56. Khanum FA, Lee SW, Kim HC, Nam C, Lee HY, Ahn SV, Oh YA, Suh I. Age-differential association between serum uric acid and incident hypertension. Sci Rep. 2019;42(3):428–37.

    Google Scholar 

  57. Cao Z, Cheng Y, Li S, Yang H, Sun L, Gao Y, Yu P, Li W, Wang Y. Mediation of the effect of serum uric acid on the risk of developing hypertension: a population-based cohort study. J Transl Med. 2019;17(1):202.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  58. Kansui Y, Matsumura K, Morinaga Y, Inoue M, Kiyohara K, Ohta Y, Goto K, Ohtsubo T, Ooboshi H, Kitazono T. Impact of serum uric acid on incident hypertension in a worksite population of Japanese men. J Transl Med. 2018;36(7):1499–505.

    CAS  Google Scholar 

  59. Zheng R, Yang T, Chen Q, Chen C, Mao Y. Serum uric acid concentrations can predict hypertension: a longitudinal population-based epidemiological study. Horm Metab Res. 2017;49(11):873–9.

    Article  CAS  PubMed  Google Scholar 

  60. Cui LF, Shi HJ, Wu SL, Shu R, Liu N, Wang GY, Zhou B, Sun K, Yu P, Wang J, et al. Association of serum uric acid and risk of hypertension in adults: a prospective study of Kailuan Corporation cohort. Clin Rheumatol. 2017;36(5):1103–10.

    Article  PubMed  Google Scholar 

  61. Yokoi Y, Kondo T, Okumura N, Shimokata K, Osugi S, Maeda K, Murohara T. Serum uric acid as a predictor of future hypertension: Stratified analysis based on body mass index and age. Prev Med. 2016;90:201–6.

    Article  PubMed  Google Scholar 

  62. Ali N, Mahmood S, Islam F. Relationship between serum uric acid and hypertension: a cross-sectional study in Bangladeshi adults. Sci Rep. 2019;9(1):9061.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  63. Yu FN, Shi YX, Cheng HY, Huang XL, Liu SS. An observational study on the relationship between serum uric acid and hypertension in a Northern Chinese population aged 45 to 59 years. Medicine. 2017;96(17):e6773.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Wu L, He Y, Jiang B, Liu M, Wang J, Zhang D, Wang Y, Zeng J. Association between serum uric acid level and hypertension in a Chinese elderly rural population. Clin Exp Hypertens. 2017;39(6):505–12.

    Article  CAS  PubMed  Google Scholar 

  65. Oyabambi AO, Areola ED, Olatunji LA, Soladoye AO. Uric acid is a key player in salt-induced endothelial dysfunction: the therapeutic role of Stigma maydis (corn silk) extract. Appl Physiol Nutr Metab. 2020;45(1):67–71.

    Article  CAS  PubMed  Google Scholar 

  66. Li P, Zhang L, Zhang M, Zhou C, Lin N. Uric acid enhances PKC-dependent eNOS phosphorylation and mediates cellular ER stress: a mechanism for uric acid-induced endothelial dysfunction. Int J Mol Med. 2016;37(4):989–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors would like to thank the members of the CHARLS as well as all participants for their contribution.

Funding

This work was supported by the NSFC (70910107022, 71130002) and National Institute on Aging (R03-TW008358-01; R01-AG037031-03S1), World Bank (7159234), and the publication fee was supported by the Support Program for Outstanding Young Talents from the Universities and Colleges of Anhui Province for Lin Zhang (gxyqZD2021118), and the Key Research Base of Humanities and Social Sciences of Universities of Anhui Province (SK2019A0223) for Wang Congzhi.

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Conceived and designed the research: LZ. Wrote the paper: LZ. Analyzed the data: LZ. Revised the paper: LZ, LY, CW, TY, DZ, HW, JL, YL, LS, XL, YH, HC and YL. All authors read and approved the final manuscript.

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Correspondence to Hengying Che or Yuanzhen Li.

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Zhang, L., Yang, L., Wang, C. et al. Individual and combined association analysis of famine exposure and serum uric acid with hypertension in the mid-aged and older adult: a population-based cross-sectional study. BMC Cardiovasc Disord 21, 420 (2021). https://doi.org/10.1186/s12872-021-02230-z

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