Diagnostic and Predictive Values of LAP in Hypertension: A Cross-Sectional Study in Chinese Population Older Than 65 Years

This study aimed to investigate the predictive value of lipid accumulation product (LAP) in hypertension in Chinese population older than 65 years. A total of 2092 adults from the communities in Pudong New Area of Shanghai were included in this cross-sectional study. The participants filled in questionnaire and received anthropometric and laboratory examinations. The receiver operating characteristics curve (ROC) was used to analyze the predictive value of different risk factors in hypertension. Results showed that LAP was closely related to hypertension (adjusted OR: 1.011, 95% CI: 1.007–1.015). In females, LAP, fasting blood glucose (FPG), and body mass index (BMI) were associated with hypertension; in males, triglycerides (TG) and waist circumference (WC) were related to hypertension. LAP (AUC = 0.655, 95% CI: 0.632–0.679) was better than neck circumference (NC) and BMI in predicting hypertension. When the cutoff value was 33.5, LAP had the best predictive performance. In males, LAP at 36.72 and 56.76 had the best predictive performance in males (AUC = 0.663, 95% CI: 0.629–0.697) and females (AUC = 0.650, 95% CI: 0.618–0.682), respectively. In conclusion, LAP is a risk factor of hypertension in the elderly. For hypertension, BMI, FPG, and LAP have favorable predictive performance in females, and WC and TG have better predictive performance in males.


Introduction
Hypertension, a significant risk factor for cardiovascular diseases and renal disorders, has been one of the most prevalent global public health problems and imposes considerable burden to the global health [1].
Obesity, abnormal accumulation lipid has been confirmed to be harmful for health, and it can raise angiotensin and aldosterone in the chronic hypoxemia population through activating fat cells, which then increases the risk for hypertension [2,3]. It has been reported that abdominal or visceral fat is superior to subcutaneous fat in the prediction of hypertension [4]. However, body mass index (BMI) is a limited indicator for the identification of anatomical location or function of different fat deposits. Kahn proposed the concept of lipid accumulation product (LAP) at the beginning of twenty-first century, and the lipid accumulation index has been used as a marker of the degree of abdominal obesity based on the ratio of waist circumference (WC) and triglyceride (TG) content [5], and it was calculated as (WC−60.6) × (TG [mmol/L]) in males and (WC−54.1) × (TG [mmol/L]) in females based on the findings from Shanghai Chinese population. In addition, LAP has been found to be also closely related to type 2 diabetes [6], cardiovascular diseases [7], hypertension [8], and ovarian syndrome [9]. LAP may be better to predict the risk of a disease according to the fat content and distribution. is study aimed to investigate the predictive value of LAP in hypertension in Chinese population older than 65 years.

Subjects.
is was a cross-sectional study with sampling survey and subjects were recruited from 11 communities in the Pudong New Area of Shanghai between January 2012 and March 2012. A total of 2092 subjects filled in the questionnaire. e mean age was 73.21 ± 6.71 years, and 46.7% was males. e inclusion criteria were as follows: subjects who lived in the communities for more than 5 years and subjects aged over 65 years and volunteered to participate in this study. e exclusion criteria were as follows: subjects who had thyromegaly or severe systemic diseases (such as liver and kidney dysfunction, cancer, heart failure, or acquired immune deficiency syndrome) and subjects who were bodybuilder, or professional or amateur athletes. All participants signed informed consent before the study.

Collection of Clinical Information.
e following clinical information was collected via a standard questionnaire: age, gender, smoking status, alcohol consumption, time of physical exercise, prior hypertension, and history of diabetes and coronary heart disease (CHD). A current smoker was defined as a person who reported smoking every day or every few days and smoked at least 100 cigarettes in lifetime. Alcohol use was defined as that a person drank alcohol containing liquid more than 20-30 g (man) or 10-20 g (woman) every day. Hypertension was defined as systolic blood pressure (SBP) ≥ 140 mmHg or diastolic blood pressure (DBP) ≥ 90 mmHg or a history of oral antihypertensive medication. CHD was defined as coronary artery stenosis of up to 50% on coronary angiography or a history of acute myocardial infarction. Diabetes was defined as fasting plasma glucose (FPG) ≥ 6.1 mmol. WC was measured through the horizontal circumference at the center of the umbilicus. Neck circumference (NC) was measured as the horizontal circumference of the neck below the Adam's apple. Height and weight were measured, and the weight-height ratio (WHR), weight-neck ratio (WNR), and BMI were calculated. Total cholesterol (TC), TG, and total bilirubin (TBIL) were used as usual indicators of lipid metabolism and reference ranges were as follows: TC: 3.1-5.2 mmol/ L, TG: 0.45-1.69 mmol/L, TBIL: 1.7-17.1 μmol/L.

Anthropometry.
e subjects were in light clothes and without shoes when the height and weight were measured. ey were measured 2 times with an interval of 10 minutes and the average was calculated during the measurement of blood pressure. e WC was measured at the level between the lower rib margin and the crista iliac. When the NC was measured, the head stretched straight, the eyes looked forward, and the horizontal measurement was conducted at the upper margin of the laryngeal prominence. BMI was calculated as weight (kg) divided by the square of height (m).

Blood Biochemical Detections.
Fasting venous blood was obtained and processed for the measurement of FPG, TG, TC, and TBIL. Blood samples were stored at −80°C before detections.

Statistical Analysis.
Quantitative data are expressed as mean ± standard deviation (SD) or median/interquartile range and qualitative data as ratio.
e Kolmogorov-Smimov test was applied to assess the normality of the data. e differences of quantitative data among patients with different hypertension statuses were analyzed with the Kruskal-Wallis H test when the data had no normal distribution. Categorical variables were analyzed with the Chi square test. Logistic stepwise regression was used to explore the risk factors with statistical significance for hypertension, and binary logistic regression to analyze the influence of each risk factor on hypertension. e association of LAP with other risk factors of hypertension was subsequently analyzed using the Spearmen correlation. e receiver operating characteristic (ROC) curve was used to analyze the predictive value of each risk factor on hypertension, and a value of P < 0.05 was considered statistically significant. Statistical analyses were performed using the Statistical Product and Service Solutions (SPSS) version 26.0 (SPSS Inc., Chicago, IL, USA).

Characteristics of Subjects at Baseline.
A total of 2092 adults were enrolled into this study. e average age was 73.21 ± 6.711 years. ere were 971 males and 1121 females. Among them, 1026 subjects had a history of hypertension, and 1066 had no history of hypertension.
ere was no significant difference in hypertension between men and women. Significant differences were noted in the age (P < 0.001), history of CHD (P < 0.001), and diabetes (P < 0.001) between subjects with hypertension and those without hypertension. ere were no marked differences in the smoking status and drinking status between subjects with and without hypertension. In addition, there were significant differences in the body weight (P < 0.001), WC (P < 0.001), NC (P < 0.001), BMI (P < 0.001), WHR (P < 0.001), and WNR (P < 0.001) between subjects with and without hypertension. Marked differences were also observed in body weight, WC, NC, WHR, and WNR between males and females. Laboratory examinations showed FGP (P < 0.001), TG (P < 0.001), alanine aminotransferase (ALT) (P < 0.001), and LAP (P < 0.001) were markedly different between subjects with and without hypertension. ere were significant differences in the TG (P < 0.001), TBIL (P < 0.001), TC (P < 0.001), and LAP (P < 0.001) between males and females (Tables 1 and 2).

Risk Factors of Hypertension. Binary logistic regression
was also used to screen related factors. Results showed that, in all the subjects, LAP (P < 0.001), FPG (P < 0.01), BMI (P < 0.01), and NC (P < 0.001) were associated with hypertension. In addition, LAP (P < 0.001), FPG (P < 0.01), and BMI (P < 0.001) were closely related to hypertension in females. However, LAP was not associated with hypertension in males. WC (P < 0.001) and TG (P < 0.001) were closely related to hypertension in males ( Figure 1).

Discussion
With the economic development and the change in lifestyle, hypertension has gradually become a serious public health problem [10]. e pathology can involve multiple organs in patients with hypertension, and the common complications of hypertension include renal failure, stroke, and cardiomyopathy caused by cardiovascular factors [11]. In China, the increase in the incidence of hypertension in rural areas is much higher than in urban areas [12].
ere is evidence showing that visceral fat can cause high blood pressure through inducing sodium retention, insulin resistance, renin-angiotensin-aldosterone activation, alteration of vascular function, and secretion of related adipokines [13].
Subcutaneous fat and visceral fat are adipose tissues that play distinct roles in the metabolism. Subcutaneous fat is a protective and safe fat storage, while visceral fat is harmful [14]. Prospective studies have shown that the abdominal obesity is an independent metabolic disorder and a risk factor of mortality as compared to the BMI and whole-body fat [15]. In subjects with abdominal obesity, visceral adipose tissue (VAT) plays an important role in the pathogenesis of metabolic diseases and cardiovascular diseases [14]. Even in nonobese people, the accumulation of VAT may still exert harmful effect. Studies have shown that the traditional obesity-related factors such as BMI and WC have limitations in the assessment of visceral or abdominal fat [8]. LAP is based on the WC and TG and can well reflect the   [5]. In most studies, LAP is calculated in the European and American, and there are significant individual differences between Chinese and European and American. In the present study, LAP was calculated according to the formula based on the accumulation of visceral and abdominal fat tissues in the Chinese provided by Huang et al. In recent years, LAP was been found to be related to the pathogenesis of cardiovascular diseases, and it also serves as a good predictor of hypertension [16].
In the study of Huang et al., LAP had diagnostic and predictive values for hypertension. In their study, the average age was 41 years, and 23.7% was the elderly. In the present study, the OR value showed the relationship between LAP and hypertension, and LAP had good predictive performance on hypertension, but the risk was relatively small as compared to it. is may be explained as the difference in the included populations among studies. In the present study, subjects older than 65 years were recruited from Shanghai. In the elderly, the elasticity of large arteries is reduced, the ability of the kidneys to maintain ion balance is also significantly compromised, and the reflex sensitivity of baroreceptor is reduced, all of which lead to the increases in the peripheral resistance and the risk of hypertension in the elderly [17]. In 1991, a Chinese epidemiological survey showed that the prevalence of hypertension was 40.4% in the subjects older than 60, and it increased to 53.2% in 2015. Kahn et al. found that LAP was decreasing over years in males, accompanied by the increase in the prevalence of hypertension. is may be one of the reasons that LAP was not associated with LAP in the male subjects older than 65 years. is also suggests that the formula for LAP should be optimized in the elderly. e ROC showed that the LAP, BMI, and FPG had good predictive performance on the risk of hypertension in males, but FPG had no close relationship with hypertension after  Variables  LAP  BMI  WHR  WNR  FPG  WC  NC  TG  LAP 1.000 0.615 * * * 0.656 * * * 0.475 * * * 0.313 * * * 0.724 * * * 0.366 * * * 0.869 * * * NC 0.366 * * * 0.565 * * * 0.411 * * * 0.163 * * * 0.2 * * * 0.729 * * * 1.000 0.180 * * * FPG 0.313 * * * 0.257 * * * 0.257 * * * 0.156 * * * 1.000 0.282 * * * 0.2 * * * 0.255 * * * BMI 0.615 * * * 1.000 0.805 * * * 0.47 * * * 0.257 * * * 0.836 * * * 0.565 * * * 0.300 * * * WC 0.724 * * * 0.836 * * * 0.929 * * * 0.703 * * * 0.282 * * * 1.000 0.729 * * * 0.334 * * * TG 0.870 * * * 0.327 * * * 0.297 * * * 0.166 * * * 0.262 * * * 0.334 * * * 0.318 * * * 1.000 Notes: number means correlation coefficient; WHR: weight-to-height ratio; WNR: weight-to-neck circumference ratio; * * * P < 0.001.        Chi-square and P value LAP 5.10 0.00239 * * 5.09 0.0241 * 16.4 0.0001 * * * * P < 0.05, * * P < 0.01, and * * * P < 0.001. 6 International Journal of Hypertension shown that LAP has a favorable predictive performance on hypertension [16,18]. is suggests that although LAP has diagnostic value on hypertension, it may seem reluctant as an independent predictor of hypertension in the present study. In addition, the predictive and diagnostic performance on hypertension was found to be different between males and females. at is, BMI, FPG, and LAP we significantly different in women, while WC and TG were comparable in females. e opposite results were found in males: significant differences were observed in the WC and TG, while marked differences were not observed in the BMI, FPG, and LAP after adjustment.
In a study which investigated the correlation between obesity and atrial fibrillation, results showed that BMI could more stably and comprehensively predict the risk of atrial fibrillation in women, but WC served as a better predictor in men [19]. Hypertension and obesity have also been proven as risk factors of atrial fibrillation [20]. ese findings may provide evidence on the differences between males and females in the present study: the predictive factors related to hypertension or cardiovascular diseases are different between males and females. In a study on the correlation between diabetes and obesity, central obesity based on WC and WHR was found as a more specific risk factor of diabetes in males as compared to that in females [21,22]. In the present study, the FPG and BMI were more closely related to hypertension in females than in males.
A cross-sectional survey showed that the FPG in patients without diabetes was significantly different between males and females [23]. e lifelong social and psychological factors (such as gender-sensitive economic, behavioral, cultural, and environmental factors) may also contribute to the differences between males and females besides the differences in the sex hormones and the expression of genderspecific genes [24,25]. Increasing studies have shown that FPG can be used to predict hypertension [26,27]. Our study also showed that FPG was related to hypertension and had predictive value on hypertension in the Chinese elderly. As compared with the relationship between FPG and hypertension in females, FPG had no relationship with hypertension in males after adjustment.
NC is the external reflection of neck adipose tissue (NAT) and reflects the subcutaneous fat deposit in the upper body. Although NAT belongs to the subcutaneous fat, it can serve as an independent disease-causing fat deposit or may explain the additional risk that cannot be predicted by the VAT [28]. When it is used to predict the risk of obesity and fat-related diseases, it can avoid the interference of breathing, food intake, and clothes as compared to WC, and it has been considered to be a reliable indicator of upper body SAT [29,30]. In a study involving 5209 subjects aged 28-62 years, results showed NC was closely related to hypertension, diabetes, and dyslipidemia, and this correlation was more evident in the females [31]. In addition, NC is also related to a variety of cardiovascular risk factors and cardiovascular diseases [32,33]. In the present study, the correlation between NC and hypertension was observed in the Chinese elderly, and NC had predictive value on hypertension. However, the predictive value of NC was not observed in males or females alone. e present study still had several limitations. First, the sample size was small, and the causal relationship between each predictor and hypertension was not further investigated. In addition, only subjects from Shanghai were included into present study, and more studies are needed to investigate the predictive value of LAP on hypertension in other areas of China.

Conclusions
LAP is closely associated with the risk of hypertension in the elderly. In the prediction of the risk of hypertension, the performance of BMI, FPG, and LAP is better in women, but the performance of WC and TG is better in men.

Data Availability
e data used to support the findings of this study are available from the corresponding author upon request.

Conflicts of Interest
e authors declare that there are no conflicts of interest regarding the publication of this study.

Authors' Contributions
Shuo Yan and Qing-Hu Zheng contributed equally to this work.