Association of Body Mass Index and Waist Circumference with Hypertension in Older Adults

Background: The relationship between obesity and prevalent hypertension in older adults has predominantly been estimated using categorical measures of body mass index (BMI) and waist circumference (WC), masking the shape of the dose-response relationship. We aimed to examine the precise relationship of BMI, WC with hypertension, and to assess the appropriate level of BMI and WC for hypertension. Methods: We examined data for 126,123 individuals in Xinzheng city aged ≥ 60 years from a population based study from January to December 2019. Logistic regression and restricted cubic spline models were applied to assess the relationship and the appropriate level of BMI and WC for hypertension. An additive interaction analysis was used to test synergistic effects between a higher BMI and WC for hypertension. Results: The full-adjusted odds ratios (ORs) with 95% condence intervals (CIs) of an increase of 1 kg/m 2 in BMI and 1 cm in WC for hypertension were 1.084 (1.080-1.087) and 1.025 (1.024-1.027), respectively. Multivariable adjusted restricted cubic spline analyses showed the nonlinear relationships of BMI and WC with hypertension in both men and women (all P<0.001). The risk of hypertension increased steeply with increasing BMI from ≥ 25 kg/m 2 and WC ≥ 88 cm or 86 cm for males and females, respectively. And we observed a signicant additive interaction between a higher BMI and WC such that the prevalence of hypertension was signicantly enhanced. Conclusion: These ndings suggest increased hypertension prevalence in the elderly population with increased BMI and WC. BMI ≤ 25 kg/m2 and WC ≤ 88 cm or 86 cm for males and females may be the best suggestion with regard to primary prevention of hypertension in older adults.


Introduction
Hypertension is a substantial public health burden [1] and a strong modi able risk factor for cardiovascular disease [2], which has become one of the leading causes of global mortality, accounting for 9.4 million deaths each year [3,4]. From 2010 to 2017, the weighted prevalence of hypertension increased by 23.4% and is increasing with aging in China [4]; therefore, the identi cation of modi able risk factors for hypertension onset has become a public health priority. Obesity is one of the modi able risk factors associated with cardiovascular disease [5][6][7], which is most generally assessed by body mass index (BMI) and waist circumference (WC). Commonly, BMI is used as a substitute for general obesity because of its strong correlation with gold standard body fat [8][9][10], and WC is regarded as a better index for evaluating abdominal obesity [11].
Accumulating evidence suggests a potential link between obesity-related hypertension [12][13][14], but controversy exists about the degree of the associations between two anthropometric indicators and the risk of hypertension. Nonetheless, information about the relationship between BMI, WC and hypertension is limited in older adults. In particular, few studies have explored the dose-response relationship and investigated the interaction between BMI and WC. Furthermore, the de nition of general overweight and obesity usually ignore ethnicity and age; and are based on their associations with chronic non-communicable diseases. Their utility in predicting hypertension remains uncertain. In addition, higher BMI and WC increase the risk of hypertension alone, but their interrelations with an increased risk of hypertension remain uncertain.
Thus, in this study, we aimed to assess the independent association of BMI and WC with hypertension as well as their possible additive interactions on the risk of hypertension using a large and contemporary population in Page 3/17 central China and to explore the appropriate level of BMI and WC for the elderly group.

2.1| Study Population
The study population consisted of participants of a comprehensive health check-up program conducted at fourteen medical examination centers (Supplementary 1). Generally, the Central People's Government of China demands that residents aged ≥ 60 years participate in health examinations annually to promote good health by enabling early detection of chronic diseases and associated risk factors. The study collected clinical, demographic, and lifestyle information from all participants by face-to-face interviews, physical examinations and blood biochemical examinations. Cross-sectional study data from Xinzheng from January to December 2019 were combined for analyses. For this study, 1969 people were excluded from the current study due to missing physical examination data (n = 117) or biochemical test data (n = 1852). Finally, we had data for 58,115 men and 68,008 women resident ≥ 60 years of age, who were enrolled to assess the association between BMI, WC and hypertension ( Fig. 1). Written informed consent was obtained from each participant before data collection. The research ethics committee of Zheng Zhou University approved the current study methodology, protocol, and procedures. (Reference Number: ZZUIRB2019-019)

2.2| Exposure
Height, weight, and WC were measured twice by trained nurses following rigorous protocols. Body height was measured without shoes with a stadiometer, and body weight was measured with participants in light clothing and without shoes by electronic scales. WC was measured with gentle breathing at the midpoint between the lowest rib and the iliac crest to the nearest 0.1 cm [15]. BMI was calculated as weight (kg) divided by the square of height (m). BMI and WC were divided into quintiles.

2.3| Outcome
Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were collected according to the World Health Organization de nition [16]. After sitting quietly for ve minutes, certi ed nurses measured each participant's seated blood pressure three times using a mercury sphygmomanometer (Omron HEM-7125, Kyoto, Japan). We calculated the means of SBP and DBP. Diagnosis of hypertension was de ned as SBP ≥ 140 mm Hg/or DBP ≤ 90 mm Hg or use of antihypertensive medication within 2 weeks [16].

2.4| Covariates
Information on demographic characteristics (age, sex, marital status, and place of residence) and behavioral measures (smoking, physical exercise and alcohol consumption) were obtained by a standardized questionnaire, which was in strict accordance with the National Standards for Basic Public Health Services (2011). Marital status was categorized as unmarried, married, divorced and death of a spouse. Smoking status was de ned as current smoker, ex-smoker, or never smoker [17]; Alcohol consumption and physical exercise status were categorized as never, once in a while, more than once a week and every day. Place of residence (rural and urban) was de ned according to country-speci c de nitions. Overnight fasting blood samples were collected into vacuum tubes for assessing serum levels of blood glucose using standard methods.

2.5| Statistical Analysis
Continuous data were expressed as the mean ± standard deviation (SD) and categorical data as the number (percentage) for quintiles of BMI or WC, using different values for men and women. Comparisons of the basic characteristics of the quintiles were performed with the χ 2 test, ANOVA, and Kruskal-Wallis test.
Logistic regression models were used to estimate the adjusted odds ratios (ORs) with 95% con dence intervals (CIs) for BMI, WC and hypertension, taking the quintile with the lowest baseline BMI or WC values as the reference. ORs and 95% CIs for hypertension were estimated for each group with adjustment of multiple confounders. One obesity parameter was introduced at a time in each model to avoid the collinear effect. Model 1 was unadjusted. Model 2 was adjusted for sex and age. Model 3 was adjusted for Model 2 and marital status, alcohol consumption, smoking, physical activity, place of residence and blood glucose. A linear trend test was performed by modeling the median value of each exposure category as a continuous variable in the models. Fully adjusted restricted cubic spline analyses were used to characterize the dose-response association and explore the potential linear or nolinear relationship of BMI, and WC with hypertension. The knots were placed at the 5th, 25th, 50th, 75th and 95th percentiles. The test result for overall association was checked rst. If the test for overall association was signi cant, the test result for nonlinearity and linearity were checked, and the P-value for nonlinear association < 0.05 indicated a signi cant result indicating the linear association. We also evaluated the additive interaction between BMI and WC for hypertension with BMI and WC analyzed as continuous variable in two categories [(BMI: BMI < 25 and BMI ≥ 25. WC: WC < 102 for males, WC < 88 for females and WC ≥ 102 for males, WC ≥ 88 for females) or (WHO proposed cut-off points[18])]. We applied three indicators to evaluate the additive interaction: relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP) or synergy index (S). RERI > 0, AP > 0, or S > 1 was regarded as a signi cant additive interaction.
Statistical analyses involved the use of SAS V .9.1 (SAS Institute) and R x64 4.0.0.All reported P values were twosided, with P < 0.05 considered statistically signi cant.

| Basic demographic characteristics
A total of 126,123 participants were eligible for inclusion in this study. The mean (SD) age was 70.29 (6.94) years. The basic demographic characteristics of the study population according to BMI and WC quintiles are shown in Table 1 and Table 2. The prevalence of hypertension, levels of alcohol consumption, physical exercise and blood glucose showed a signi cant progressive increase from the quintile with the lowest BMI to the quintile with the highest BMI. This was also the case for the WC quintiles.

3.3| Dose response analysis
Multivariable adjusted restricted cubic spline analyses showed the nonlinear relationships of BMI with hypertension (all P < 0.001; Figure. The results of the dose-response relationship analysis between WC and hypertension are shown in Figure.3 was over 88 cm and 86 cm for males and females, respectively, WC was more steeply positively associated with the risk of hypertension ( Figure.3.B; Figure.3.C).

3.4| Additive interaction analysis
We observed a signi cant additive interaction between higher BMI and WC such that the prevalence of

Discussion
In this study, the prevalence of hypertension increased with rising BMI and WC in the older population of Xinzheng, China, in males and females and in the entire study population. These associations remained signi cant after adjustment for multiple factors and restricted cubic spline analysis showed clear dose-response relationships. To our knowledge, this is the rst study to research the association between BMI, WC and hypertension risk in an older Chinese population. At the same time, this study conducted an additive interaction analysis, which concluded a signi cant additive interaction between BMI and WC such that the prevalence of hypertension increased. To some extent, this study provides a better understanding of the association of anthropometric indicators of obesity with hypertension rather than focusing on individual indices, which would be more enlightening for hypertension prevention.
Our results are consistent with most previous studies that showed that the risk of hypertension increases with rising BMI [14,19]. The "Look up 7+" epidemiological study showed that blood pressure increased signi cantly across BMI levels [20], which indicated that there was not only a strong relationship between BMI and hypertension, but also an association between the continuous variables of BMI and blood pressure. Our study con rmed that there was a nonlinear dose-response relationship between BMI and the risk of hypertension, which was similar to previous studies [21,22]. However, a prospective study including 1412 subjects provided evidence that an increase in BMI is associated with a linearly increased adjusted risk of developing conditions with high hypertension risk [23], possibly because of estimating the relationship using categorical measures of BMI, masking the shape of the dose-response relationship. Furthermore, in our large sample (n = 126123), BMI below 25 kg/m 2 was regarded as a healthy weight for the elderly in terms of hypertension prevalence. However, our proposed appropriate level for hypertension were higher than those in some previous studies [24], which could be due to differences in the age range. The average age we sampled was much higher because BMI is greater in older populations, which might be a reason for the inconsistent ndings, and when one of the studies strati ed data by age (< 50 and ≥ 50 years), the appropriate level for the older group was 25 kg/m 2 for men and women [25]. Contrary to the three studies above, the NHANES study suggested 27 kg/m 2 as the value [26], but there may be innate or cultural differences between the U.S. and Asia, including dietary habits, macronutrient content, and physical activity habits. Given the marked variations in different world regions, countries and populations within countries, the use of uni ed range may underestimate or overestimate the health hazards [27]; thus, it is of great interest to determine the appropriate level for cardiovascular disease risks.
For WC, the relationship with hypertension was reported by most studies [28,29]. Most studies have found a positive association between WC and hypertension [30], whereas a null association was found in a prospective study from European populations [29]. The low participation rate and the relatively high study drop-out rate may bias the result. We highlighted the increased risk of hypertension when WC was over 88 cm and 86 cm for males and females, respectively. Our proposed WC appropriate level is higher than those reported by M Gus et al [31]. As early as 2009, they suggested that the best range to predict hypertension were 87 cm in men and 80 cm in women, and increasing WC over time could be the cause of the difference. The worldwide upward trend in obesity has been dramatic; from 2013 to 2018, the mean WC increased from 82 cm to 86.3 cm for men and from 79.1 cm to 83.4 cm for older women [32]. However,lower appropriate level were suggested by previous studies [33,34], and ethnic and racial differences might explain the discrepancy between different studies.
In China, rapid economic development and associated dramatic lifestyle changes have led to a substantial increase in the prevalence of obesity and related noncommunicable diseases, including cardiovascular diseases, which is concerning for a developing country with a population of 1.37 billion. To our knowledge, the present study is the rst to report a synergistic effect of higher BMI and WC on the risk of hypertension in the aged. In other words, the copresence of higher BMI and WC greatly increased the risk of hypertension, more than the summation of the risks due to exposure to either of them. In a cohort of 17,803 pregnant Chinese women, the copresence of a higher BMI and WC interacts to further increase the risk of gestational diabetes mellitus [35]. In addition, RISKESDAS research showed that only when general obesity or overweight coexisted with central obesity was the prevalence of hypertension signi cantly increased [13]. This nding supported the stable relation between excess body fat and blood pressure. It is generally believed that the increased body mass would raise blood volume and cardiac output and then lead to the inadequate vasodilatation while the increased activity of the sympathetic nervous system, abnormal rennin-angiotensin-aldosterone relation and insulin resistance would contains data related to physical measurements and disease, but also includes information on demographic characteristics, physical activity, daily living habits and some blood biochemical tests, therefore, we can make full use of this information for a more comprehensive and reliable analysis.

Conclusion
Understanding the association between BMI, WC and risks of hypertension is very important because various interpretations can lead to con icting recommendations of ideal BMIs and WCs among the elderly. The results of this study revealed that being as lean as possible within the normal range may be a best suggestion in reducing the risks of hypertension. However, further cohort studies and replication studies in Chinese and other populations are needed before the results can be used in clinical practice to detect high-risk elderly individuals for early intervention.  Dose-response relationship between BMI and hypertension Figure 2 BMI and hypertension outcomes in the total study population (A), male study population (B) and female study population (C). The associations were adjusted for age, marital status, alcohol consumption, smoking, physical activity, area and blood glucose. The solid lines