Hidden burden of hypertension in Arab adolescents linked to obesity, dyslipidemia, and vitamin D status

Abstract

The present study aims to investigate the prevalence of undiagnosed hypertension (HTN) in Saudi adolescents and identify the potential interactions between vitamin D (VD) and dyslipidemia (DLD) in the context of HTN. This cross-sectional study included 4760 apparently healthy adolescents aged 14.4 ± 1.6 years (64% girls). Anthropometrics, fasting glucose, lipid profiles [triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL–C), low-density lipoprotein cholesterol (LDL–C)], and serum 25(OH)D [deficiency < 50 nmol/l (20 ng/mL); sufficient ≥ 50 nmol/l (20 ng/mL)] were measured. Undiagnosed HTN was defined as adolescent who has systolic or diastolic BP ≥ 95th percentile (for age, sex and height) and not received a diagnosis of high BP or HTN from a physician or healthcare professional and who was not on any antihypertensive medication. Results showed high prevalence of undiagnosed HTN (21.1%), VD deficiency (VDD) (84.4%), and DLD (22%) among participants. Abnormal lipids were significant risk factors for HTN in overall participants [low–HDL–C, OR = 1.3, 95%CI: 1.1–1.5, p < 0.001; high–LDL–C, OR = 1.2, 95%CI: 1.0–1.4, p = 0.01], which persisted only in girls [low–HDL–C, OR = 1.4, 95%CI: 1.1–1.6, p = 0.001; high–LDL–C, OR = 1.3, 95%CI: 1.1–1.6, p = 0.008]. Hypertriglyceridemia and VDD were not found to be significant risk factors for HTN. Obesity showed the strongest association with HTN [OR = 1.7, 95%CI: 1.4–2.2, p < 0.001]. VD has significant inverse relationship with SBP in both genders but not with DBP. This study found significant sex differences in the prevalence of lipid abnormalities, where hypertriglyceridemia and low–HDL–C were more common in boys (24.4% vs. 20.7% and 61.8% 51.9%, respectively), while high–LDL–C was more prevalent in girls (60.4% vs. 50.3%). In conclusion, we revealed a critical high prevalence of undiagnosed HTN among Saudi adolescents, with sexual dimorphisms in associated risk factors. Obesity and DLD were exposed as risk factors for adolescent HTN rather than VDD. The lack of significant association between VD and HTN needs further investigation. Our results highlight the necessity for national awareness and intervention programs for the early detection and management of HTN through regular screening and follow-up, which can have crucial long-term benefits.

Introduction

The global prevalence of childhood HTN is approximately 4%¹. Childhood HTN increases the risk of developing HTN in adults, and the early detection and management of high blood pressure (BP) could prevent nearly 10% of adulthood HTN². Moreover, childhood HTN is linked to target organ damage including greater carotid intima-media thickness (indicative of atherosclerosis), left ventricular hypertrophy, proteinuria (indicative of renal impairment), and decreased executive functioning in children^3–6. Childhood HTN combined with obesity are considered the main predictors of adult HTN, leading to a higher risk for cardiovascular mortality in adults⁷. Furthermore, HTN is considered a leading cause of mortality and disease burden, where the coexistence of HTN with other risk factors for cardiovascular diseases (CVDs) results in increased rates of morbidity and mortality⁸. In this regard, the large INTERHEART study, which included 29,972 participants from 52 countries, indicated that the total CVDs risk could be increased threefold with the existence of a single cardiovascular risk factor, whereas in the same individual, the coexistence of HTN, DLD, smoking, or type 2 diabetes mellitus (T2DM) can result in a more than 20-fold increase in CVDs risk compared with individuals affected only with HTN⁹.

A Previous Saudi a national survey screened for HTN has reported a prevalence of self-reported HTN by 7.1%, while the measured BP of screened participants showed a prevalence of HTN by 15.2% with 57.8% of hypertensive individuals being undiagnosed¹⁰. This finding underscores the critical need for screening to detect individuals with undiagnosed HTN, as this can have substantial effects on public health. Saudi large-scale epidemiologic data about undiagnosed HTN children is scarce, with most studies included small sample sizes. A previous cross-sectional study conducted in the Eastern Province of Saudi Arabia, reported that 30% of children had HTN, the study included 146 boys and girls aged 13–16 years from intermediate and secondary schools¹¹. Another school-based cross-sectional study found that 17.2% of participants had HTN, the study included 400 male adolescents aged 15–17 years in the Northern Province of Saudi Arabia¹²,.

Current research evidence indicates that HTN is associated with various risk factors, such as inadequate intake of fruits and vegetables, high sodium consumption, sedentary behaviors, being overweight or obese, and smoking^13,14, such factors that Saudi suffer from, as Saudi Arabia is experiencing a nutritional transition characterized by the adoption of westernized diets in place of traditional dietary patterns, alongside a decline in physical activity levels^15,16. This change in dietary habits and sedentary behavior have been linked to increased prevalence of obesity and related health conditions including HTN^17,18.

DLD is a disorder of blood lipid levels commonly associated with environmental factors such as a sedentary lifestyle, obesity, and excessive intake of saturated fat. DLD is usually characterized by increased TG and decreased HDL–C levels, which leads to an elevation in non-HDL–C, a pattern of lipid abnormalities termed ‘atherogenic DLD’, which has been observed in more than 40% of obese American adolescents¹⁹. DLD and HTN have a common pathophysiology in relation to obesity, therefore, individuals with both conditions are at greater risk for adverse effects to the cardiovascular health²⁰. Previously, it was proposed that cardiovascular events in adulthood could be delayed or reduced by screening for DLD in childhood^21,22. However, most of the research investigating the prospective effects of the combination of DLD and HTN has been done in adults and little research conducted in adolescents.

VD is a cholesterol-based molecule²³. Observational and interventional studies have shown that VD deficiency (VDD) is linked to lipid abnormalities, whereas sufficient VD levels are associated with good lipid profiles. A recent large study included more than 20,000 participants analyzed VD levels and different fractions of lipids, has found that deficient levels of VD were significantly associated with the atherogenic lipid profile²⁴. Additionally, a recent large meta-analysis assessing the effects of VD supplementation on HDL–C, TC, TG, and LDL–C, the authors reported statistically significant inverse correlations between VD supplementation and TC, TG, and LDL–C, whereas HDL–C levels have increased²⁵. Moreover, VDD has been proposed to contribute to elevated BP through several biological mechanisms. 1,25-dihydroxyvitamin D suppresses renin gene expression via the its receptor, thereby inhibiting the renin-angiotensin-aldosterone system (RAAS); VDD could lead to RAAS overactivation, increased vasoconstriction, sodium retention, and HTN²⁶. VDD is also linked to endothelial dysfunction through reduced nitric oxide (NO) bioavailability and impaired endothelial nitric oxide synthase (eNOS) activity, as well as increased arterial stiffness, both of which raise vascular resistance and systolic BP²⁷. Additionally, secondary hyperparathyroidism in VDD may promote vasoconstriction through altered vascular calcium handling^25–28.

Early detection of HTN in childhood and recognizing the associated risk factors is crucial in the prevention of future morbidities later in adulthood. The present cross-sectional study screened for the prevalence of undiagnosed HTN, and investigated the associations of VD status and lipid abnormalities in relation to HTN, in a large group of normoglycemic Saudi adolescents recruited form Riyadh city in the geographic center of Saudi Arabia and the center of the Arabian Peninsula.

Methods

Study population

This cross-sectional study included a total of 4,673 apparently healthy school-attending Saudi adolescents aged 14.4 ± 1.6 (64% girls) from 60 randomly selected preparatory and high schools. A written informed consent was obtained from the participants’ parents or legal guardian before inclusion in the study. All participants were instructed to come to their respective school in an overnight fasting state. Exclusion criteria was participants who had previously been diagnosed with HTN, CVDs, or diabetes, who had been prescribed BP or lipid lowering medications, who are following a specific diet, or who are taking VD supplementation. After inclusion, participants who were diagnosed with prediabetes or T2DM on the basis of their fasting glucose level [≥ 100 mg/dL (5.6 mmol/L)] were also excluded, according to the criteria of the American Diabetes Association²⁹ (Fig. 1). This study was approved by the Institutional Review Board at College of Medicine, King Saud University, Riyadh, Saudi Arabia (No. E-19–4239, 29 October 2019). All procedures were conducted in compliance with the ethical standards of the Helsinki Declaration of 1964 and its most recent amendments.

Fig. 1.

Flow chart.

Anthropometric and biochemical analyses

Trained nurses assessed anthropometrics, which included height (cm), weight (kg), body mass index (BMI) (kg/m²), waist (cm), and hip (cm) circumferences. Systolic and diastolic BP were measured as the average of two readings with a 15-min interval, using pediatric cutoffs appropriate for children’s sizes with cuff wrapped snugly around the arm and allowed two fingers to fit underneath comfortably³⁰. students were seated in the assembly room with their right arm supported at heart level and rested for 30 min before measurement. BP was assessed using calibrated Omron M3W electronic sphygmomanometer (HEM-7202-E, OMRON Healthcare Co., Ltd, Kyoto, Japan), a device endorsed by the European Society of HTN International Protocol³¹. Blood samples were collected in the morning in a 10-hour fasting state. After blood was collected, it was placed in red-top tubes and allowed to clot at room temperature (25 °C) for 30 to 60 min. The tubes were then centrifuged for 10 min at a force 1500× g in a refrigerated centrifuge (4 °C) to separate the serum from the clot. The resulting serum was then immediately aliquoted, labeled, and sent to the Chair for Biomarkers of Chronic Diseases (CBCD) at King Saud University (KSU), Riyadh, Saudi Arabia, to be stored at −80 °C until assessments. The collected serum samples were used to measure parameters of interest. Standard routine laboratory analysis (Konelab 20 Thermo-Fischer, Espoo, Finland) was used to measure TG, TC, HDL–C, and fasting glucose levels³². LDL–C was calculated using the Friedwald formula. Serum 25-hydroxyVD (25(OH)D) levels were measured using an electrochemiluminescence immunoassay (Cobas e411), a Roche Elecsys modular analytics system (Roche Diagnostics, GmbH, Germany) as previously done³³. The analysis utilized commercially available enzyme-linked immunosorbent assay (ELISA) kits (IDS Ltd., Boldon Colliery, Tyne & Wear, UK), with inter and intra-assay variation of 5.3% and 4.6%, respectively, demonstrating 100% cross-reactivity with 25-hydroxyvitamin D3 and 75% cross-reactivity with 25-hydroxyvitamin D2. All samples were analysed in CBCD, KSU, Riyadh, Saudi Arabia. CBCD is a participant in the VD External Quality Assessment Scheme (DEQAS). Furthermore, the laboratory adheres to quality assurance standards as stipulated by ISO 9000 and ISO 17,025, with regular audits conducted by the department.

Definitions and cut-offs

HTN was defined based on the 2017 clinical practice guidelines of the American Academy of Pediatrics (AAP); systolic and/or diastolic BP (SBP and DBP, respectively) ≥ 95th percentile for age, sex and height³⁴, accordingly, our participants were grouped into two groups (HTN group and non-HTN group); DLD cutoffs were based on the criteria of the National Cholesterol Education Program (NCEP) Expert Panel on Cholesterol Levels for children; hypertriglyceridemia, serum TG levels ≥ 90 mg/dL (≥ 1.0 mmol/L); HDL–C levels < 40 mg/dL (< 1.0 mmol/L); LDL–C levels ≥ 110 mg/dL (≥ 2.8 mmol/L)³⁵. Obesity was defined according to the international age-and sex-specific child cutoff points of the International Obesity Task Force (IOTF) criteria³⁶, accordingly participants were grouped into two groups (normal BMI group and overweight/obese group). VD status was defined on the basis of national and regional recommendations: deficiency < 50 nmol/l (20 ng/mL); sufficient > 50 nmol/l (20 ng/mL), ³⁷accordingly participants were grouped into two groups (sufficient group and deficient group).

Data analysis

Data were analysed using Statistical Package for the Social Sciences (SPSS), version 22 Chicago, IL, USA. Continuous data are presented as the means ± standard deviations (SDs) and medians (1st and 3rd percentiles) for variables following Gaussian and non-Gaussian distribution, respectively. Categorical data are presented as frequencies and per-centages (%). Associations between variables were determined via chi-square tests and Fisher’s exact tests. All continuous variables were checked for normality via the Kolmogorov‒Smirnov test. Non-normal variables were log-transformed. Differences in groups were analyzed via independent Student’s t test and one-way analysis of variance (ANOVA) for normal variables. Mann–Whitney U-test and Kruskal-Wallis test were used to analyze the differences in groups for non-normal variables. Pearson correlation analysis was used to examine the correlations between the parameters of interest. Multinomial logistic regression analysis was used to identify associations and risk factors for HTN with lipid abnormalities, VDD, and obesity statuses. Figures were plotted in MS Excel. A p value < 0.05 was considered significant.

Results

Differences in the demographic and clinical characteristics of participants are shown in Table 1. We found high prevalence of undiagnosed HTN (21.1%) and VDD (84.4%) among participants. The prevalence of DLD indices was as follows; high–LDL–C levels (56.8%), low–HDL–C (55.5%), and hypertriglyceridemia (22%). Mean SBP was significantly higher in boys than girls [116.2 ± 14.3 vs. 115.01 ± 15.9, p = 0.04], whereas DBP was significantly higher in girls than boys [72.5 ± 12.2 vs. 67.8 ± 10.2, p < 0.001]. Hypertriglyceridemia and low–HDL–C levels were more prevalent in boys than in girls (hypertriglyceridemia, 24.4% vs. 20.7%, p = 0.003; low–HDL–C, 61.8% vs. 51.9%, p < 0.001), whereas high–LDL–C levels were more prevalent in girls than in boys [60.4% in girls vs. 50.3% in boys, p < 0.001]. Compared to girls, boys had significantly higher serum VD levels [39.8 ± 15.4 nmol/l vs. 29.8 ± 14.5 nmol/l, p < 0.001]. The prevalence of VDD was higher in girls (89.4%) than in boys (75.2%), p < 0.001. Overweight/obese status was more prevalent in boys than in girls [38.3% vs. 34.3%, p = 0.006].

Table 1.

Comparison of the characteristics of participants according to sex.

Parameter	All	Boys	Girls	p value	Age adjusted p value
N	4672	1664	3008
Age (year)	14.4 ± 1.6	14.6 ± 1.6	14.3 ± 1.6	< 0.001
BMI (kg/m2)	22.5 ± 5.8	22.7 ± 6.3	22.4 ± 5.5	0.06	0.2
BMI Z Score	−0.01 ± 0.99	0.03 ± 1.1	−0.03 ± 0.94	0.06	0.2
SBP (mmHg)	115 ± 15	116 ± 14	115 ± 15	0.008	0.04
DBP (mmHg)	70 ± 11	67 ± 10	72 ± 12	< 0.001	< 0.001
TG (mmol/l)	1.1 ± 0.4	1.12 ± 0.5	1.06 ± 0.4	< 0.001	< 0.001
TC (mmol/l)	4.2 ± 0.8	4.1 ± 0.8	4.2 ± 0.8	< 0.001	< 0.001
HDL–C (mmol/l)	1.01 ± 0.3	0.98 ± 0.2	1.04 ± 0.3	< 0.001	< 0.001
LDL–C (mmol/l)	2.7 ± 0.7	2.6 ± 0.7	2.7 ± 0.8	< 0.001	< 0.001
25(OH)D (nmol/l)	33.3 ± 15.6	39.8 ± 15.4	29.8 ± 14.5	< 0.001	< 0.001
HTN N (%)	987 (21.1)	357 (21.3)	630 (20.9)	0.7
DLD N (%) Hypertriglyceridemia Low–HDL–C High–LDL–C	1029 (22) 2593 (55.5) 2652 (56.8)	406 (24.4) 1029 (61.8) 836 (50.3)	623 (20.7) 1564 (51.9) 1816 (60.4)	0.003 < 0.001 < 0.001
VDD N (%) Deficient Sufficient	3942 (84.6) 730 (15.4)	1252 (75.2) 412 (24.8)	2690 (89.4) 318 (10.6)	< 0.001 < 0.001
Overweight/Obese N (%)	1669 (35.7)	638 (38.3)	1031 (34.3)	0.006

Data are presented as the means±SDs, and the p value is significant at the 0.05 level. BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; TG, triglycerides; TC, total cholesterol; HDL–C, high−density lipoprotein cholesterol; LDL–C, low−density lipoprotein cholesterol; HTN, hypertension; DLD, dyslipidemia; VDD, vitamin D deficiency.

Table 2 shows the clinical characteristics of participants according to BP status. Compared to the non-HTN group, HTN group had significantly higher levels of LDL–C (2.8 ± 0.8 vs. 2.6 ± 0.6, p = 0.03), and significantly lower levels of HDL–C (0.97 ± 0.2 vs. 1.05 ± 0.4, p < 0.001). Prevalence of atherogenic DLD components was significantly higher in the HTN group than in non-HTN group (high–LDL–C, 61.6% vs. 55.5%, p = 0.001; low–HDL–C, 63.8% vs. 53.2%, p < 0.001) hypertriglyceridemia, 23.8% vs. 21.5%, p = 0.1). Prevalence of VDD was significantly higher in the HTN group than in non-HTN group (87.3% vs. 83.6%, p = 0.04). Similarly, the prevalence of overweight/obesity was significantly higher in the HTN group than in non-HTN group (50% vs. 32%, p < 0.001).

Table 2.

Comparison of the characteristics of participants according to BP status.

Parameter	Non-HTN	HTN	p value	Age and BMI adjusted p value
N	3685	987
Age (year)	14.4 ± 1.6	14.7 ± 1.5	< 0.001
BMI (kg/m2)	21.9 ± 5.4	24.8 ± 6.6	< 0.001
BMI Z Score	−0.11 ± 0.9	0.38 ± 1.1	< 0.001
TG (mmol/l)	1.1 ± 0.3	1.1 ± 0.6	0.001	0.5
TC (mmol/l)	4.1 ± 0.7	4.26 ± 0.9	0.04	0.2
HDL–C (mmol/l)	1.05 ± 0.4	0.97 ± 0.2	< 0.001	< 0.001
LDL–C (mmol/l)	2.6 ± 0.6	2.8 ± 0.8	0.002	0.03
25(OH)D (nmol/l)	33.6 ± 15.9	32.3 ± 14.1	0.01	0.2
DLD N (%) Hypertriglyceridemia Low–HDL–C High LDL–C	794 (21.5) 1962 (53.2) 2045 (55.5)	237 (23.8) 629 (63.8) 607 (61.6)	0.1 < 0.001 0.001
VDD N (%) Deficient Sufficient	3080 (83.6) 605 (16.4)	862 (87.3) 125 (12.7)	0.04 0.02
Overweight/Obese N (%)	1175 (32)	494 (50)	< 0.001

Data are presented as the means±SDs, and the p value is significant at the 0.05 level. BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; TG, triglycerides; TC, total cholesterol; HDL–C, high−density lipoprotein cholesterol; LDL–C, low−density lipoprotein cholesterol; HTN, hypertension; DLD, dyslipidemia; VDD, vitamin D deficiency.

Figure 2 shows the prevalence of HTN according to the number of lipid abnormalities. In all participants, there was a significant increase in the prevalence of HTN with clustering of lipid abnormalities (p = 0.004), which was more evident in boys (31.5% had full DLD p < 0.001) compared to girls (25.5% had full DLD p < 0.01).

Fig. 2.

Prevalence (%) of HTN according to the accumulation of lipid abnormalities; 0; represents no lipid abnormalities; 1 or 2: represents the presence of abnormal levels of 1 or 2 DLD indices (high TG, low HDL–C, or high LDL–C); full DLD: represents the presence of abnormal levels of the three DLD indices (high TG, low HDL–C, and high LDL–C).

Figure 3 shows the prevalence of obesity according to the number of lipid abnormalities. In all participants, there was a significant increase in the prevalence of obesity with clustering of lipid abnormalities (p = 0.001), which was more evident in boys with full DLD (71.9%, p < 0.001) compared to girls with full DLD (51.2% had full DLD p < 0.01).

Fig. 3.

Prevalence (%) of overweight/obesity according to presence of lipid abnormalities; 1 or 2: represents the presence of abnormal levels of 1 or 2 DLD indices (high TG, low HDL–C, or high LDL–C); full DLD: represents the presence of abnormal levels of the three DLD indices (high TG, low HDL–C, and high LDL–C).

Table 3 shows clinical characteristics of study participants according to VD status. Adolescents with deficient VD levels had higher SBP (115.8 vs. 112.4, p < 0.001) and higher DBP (71.1 vs. 68.8, p < 0.001). Additionally, DLD was more common in VD deficient individuals (hypertriglyceridemia, 22.7% vs. 18.9%, p = 0.03; low–HDL–C, 55.9% vs. 49.7%, p = 0.004). Similarly, obesity and HTN were more common among VD deficient individuals (obesity, 36.8% vs. 29.1%, p < 0.001; HTN, 21.8% vs. 15.9%, p = 0.001).

Table 3.

Comparison of the characteristics of participants according to VD status.

Parameter	Sufficient (≥ 50 nmol/l)	Deficient (< 50 nmol/l)	p value	BMI adjusted p value
N	730	3942
Age (year)	14.3 ± 1.6	14.4 ± 1.5	0.1
BMI (kg/m2)	21.4 ± 5.3	22.6 ± 5.8	< 0.001
BMI Z Score	−0.18 ± 0.92	0.01 ± 1.01	< 0.001
SBP (mmHg)	112.4 ± 14.2	115.8 ± 15.4	< 0.001	< 0.001
DBP (mmHg)	68.8 ± 10.6	71.1 ± 12.01	< 0.001	< 0.001
TG (mmol/l)	1.04 ± 0.4	1.1 ± 0.5	0.01	0.1
TC (mmol/l)	4.17 ± 0.8	4.2 ± 0.8	0.3	0.5
HDL–C (mmol/l)	1.03 ± 0.3	1.01 ± 0.3	0.09	0.3
LDL–C (mmol/l)	2.66 ± 0.7	2.7 ± 0.8	0.3	0.2
HTN N (%)	97 (15.9)	860 (21.8)	0.001
DLD N (%) Hypertriglyceridemia Low–HDL–C High–LDL–C	119 (18.9) 310 (49.7) 336 (53.8)	918 (22.7) 2262 (55.9) 2322 (57.4)	0.03 0.004 0.09
Overweight/Obese N (%)	177 (29.1)	1489 (36.8)	< 0.001

Data are presented as the means±SDs, and the p value is significant at the 0.05 level. BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; TG, triglycerides; TC, total cholesterol; HDL–C, high−density lipoprotein cholesterol; LDL–C, low−density lipoprotein cholesterol; HTN, hypertension; DLD, dyslipidemia; VDD, vitamin D deficiency.

Table 4 shows clinical characteristics of study participants according to obesity status. Overweight/obese adolescents had significantly higher SBP (120.1 vs. 112.9, p < 0.001) and higher DBP (72.5 vs. 69.9, p < 0.001). Additionally, overweight/obese adolescents had significantly higher prevalence of VDD (89.2% vs. 85.3%, p = 0.001) and higher prevalence of HTN (29.5% vs. 16.4%, p < 0.001).

Table 4.

Comparison of the characteristics of participants according to obesity status.

Parameter	Normal BMI	Overweight/Obese	p value
N	3003	1669
Age (year)	14.4 ± 1.6	14.5 ± 1.5	0.08
SBP (mmHg)	112 ± 14	120 ± 15	< 0.001
DBP (mmHg)	69 ± 11	72 ± 12	< 0.001
TG (mmol/l)	1.01 ± 0.4	1.2 ± 0.5	< 0.001
TC (mmol/l)	4.1 ± 0.8	4.3 ± 0.8	< 0.001
HDL–C (mmol/l)	1.05 ± 0.3	0.96 ± 0.2	< 0.001
LDL–C (mmol/l)	2.6 ± 0.7	2.7 ± 0.8	< 0.001
25(OH)D (nmol/l)	33.9 ± 15.9	32.2 ± 14.7	< 0.001
HTN N (%)	493 (16.4)	492 (29.5)	< 0.001
DLD N (%) Hypertriglyceridemia Low–HDL–C High–LDL–C	516 (17.2) 1510 (50.3) 1643 (54.7)	513 (30.8) 1081 (64.8) 1009 (60.5)	< 0.001 < 0.001 < 0.001
VDD N (%) Deficient Sufficient	1523 (85.3) 431 (14.7)	875 (89.2) 177 (10.8)	0.001 0.001

Data are presented as the means±SDs, and the p value is significant at the 0.05 level. BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; TG, triglycerides; TC, total cholesterol; HDL–C, high−density lipoprotein cholesterol; LDL–C, low−density lipoprotein cholesterol; HTN, hypertension; DLD, dyslipidemia; VDD, vitamin D deficiency.

Table 5 shows correlations of SBP and DBP with serum lipids and VD. Overall, SBP and DBP had significant weak relationship with parameters of interest. BMI had a positive relationship with SBP and DBP in overall participants and in both sexes (p < 0.01). TG had a positive relationship with both SBP and DBP only in boys (p < 0.001) but not in girls (p > 0.05). HDL–C had an inverse relationship with SBP in overall participants, which was persistence in both sexes, p < 0.001, while HDL–C was inversely correlated with DBP only in girls but not in boys. LDL–C had a positive relationship with both SBP and DBP only in girls (p < 0.001) but not boys. VD had a significant inverse relationship with SBP (p < 0.01) and in both sexes (in boys, r = −0.12, p < 0.01; in girls, r = −0.05, p < 0.05), while no significant correlation was found between VD and DBP (p > 0.05).

Table 5.

Correlation analysis of SBP and DBP with measured parameters.

Parameters	ALL		Boys		Girls
	SBP	DBP	SBP	DBP	SBP	DBP
BMI	0.29**	0.14**	0.40**	0.16**	0.24**	0.15**
TG	0.04*		0.12**	0.06**
TC		0.05**				0.04*
HDL–C	−0.15**	−0.07**	−0.15**		−0.15**	−0.12**
LDL–C	0.04**	0.08**			0.06**	0.08**
25(OH)D	−0.06**	−0.07	−0.12**		−0.05*

Note: Data presented as coefficient (R).*and**represented p−value significant at 0.05 and 0.01 level respectively. SBP, Systolic Blood Pressure; DBP, Diastolic Blood Pressure; BMI, Body Mass Index; TG, Triglycerides; TC, Total Cholesterol; HDL–C, High−Density Lipoprotein Cholesterol; LDL–C, Low−Density Lipoprotein Cholesterol.

HTN risk factors were assessed using multinomial logistic regression analyses with lipid-abnormality, VDD, and obesity statuses as independent variables and HTN as a dependent variable (Table 6). The age- and BMI-adjusted models showed that low–HDL–C serum levels was a significant risk factor for HTN in overall participants [OR = 1.3, 95%CI: 1.1–1.5, p < 0.001], which was persistent only in girls [OR = 1.4, 95%CI: 1.1–1.6, p = 0.001] but not in boys. Similarly, high–LDL–C serum levels was a significant risk factor for HTN in overall participants [OR = 1.2, 95%CI: 1.0–1.4, p = 0.01] and persisted only in girls [OR = 1.3, 95%CI: 1.1–1.6, p = 0.008]. While VDD did not show as a significant risk factor for HTN among our study population. Being overweight/obese was a significant risk factor for HTN [OR = 1.7, 95%CI: 1.4–2.2, p < 0.001], which was more evident in boys than in girls [boys, OR = 2.8, 95%CI: 1.8–4.2, p < 0.001; girls, OR = 1.5, 95%CI: 1.2–1.9, p = 0.001].

Table 6.

Risk factors for HTN among the study participants.

	All		Boys		Girls
	Model 1 OR (95%CI), p value	Model 2 OR (95%CI), p value	Model 1 OR (95%CI), p value	Model 2 OR (95%CI), p value	Model 1 OR (95%CI), p value	Model 2 OR (95%CI), p value
DLD Hypertriglyceridemia Low–HDL–C High–LDL–C	1.07 (0.9–1.3), p = 0.4 1.6 (1.4–1.8), p < 0.001 1.3 (1.2–1.6), p < 0.001	1.0 (0.8–1.2), p = 0.9 1.3 (1.1–1.5), p < 0.001 1.2 (1.0–1.4), p = 0.01	1.5 (1.2–1.9), p = 0.002 1.6 (1.2–2.1), p < 0.001 1.3 (1.0–1.7), p = 0.02	1.3 (1.0–1.8), p = 0.4 1.2 (0.9–1.5), p = 0.2 1.1 (0.9–1.4), p = 0.3	0.9 (0.7–1.1), p = 0.4 1.5 (1.3–1.8), p < 0.001 1.3 (1.1–1.6), p = 0.003	0.8 (0.6–1.0), p = 0.1 1.4 (1.1–1.6), p = 0.001 1.3 (1.1–1.6), p = 0.008
VDD Sufficient Deficient	1 1.5 (1.2–1.9), p = 0.001	1 1.3 (0.9–1.8), p = 0.06	1 1.7 (1.2–2.3), p = 0.001	1 1.4 (0.9–1.9), p = 0.57	1 1.3 (0.9–1.8), p = 0.1	1 1.2 (0.9–1.7), p = 0.2
Overweight/Obese No Yes	1 2.1 (1.8–2.5), p < 0.001	1 1.7 (1.4–2.2), p < 0.001	1 2.7 (2.2–3.5), p < 0.001	1 2.8 (1.8–4.2), p < 0.001	1 1.84 (1.5–2.2), p < 0.001	1 1.5 (1.2–1.9), p = 0.001

Multivariate logistic regression analysis was used to assess the HTN risk factors according lipid−abnormality, VDD, and obesity statuses. Model−1 unadjusted, and model−2 adjusted for age and BMI. Data are presented as presented as OR (95%CI), p–value, and the p value is significant at the 0.05 level. DLD, dyslipidemia; HDL–C, high−density lipoprotein cholesterol; LDL–C, low−density lipoprotein cholesterol; VDD, vitamin D deficiency.

Discussion

The present study found high prevalence of undiagnosed HTN among Saudi adolescents, where 21.1% of participants had either high SBP or DBP. This is higher than what has been reported in previous Saudi studies. A recent Saudi study included 380 boys and girls aged 15–19 years (199 boys) that reported a prevalence of HTN by 16.75% and 23.2% among boys and girls respectively³⁸. [Reference 37 should now be 38 and be Al-Daghri NM, Amer OE, Khattak MNK, Sabico S, Ghouse Ahmed Ansari M, Al-Saleh Y, Aljohani N, Alfawaz H, Alokail MS. Effects of different vitamin D supplementation strategies in reversing metabolic syndrome and its component risk factors in adolescents. J Steroid Biochem Mol Biol. 2019 Jul;191:105378. doi: 10.1016/j.jsbmb.2019.105378. The rest of the references from 38 to last should be adjusted]. Ghamri et al. in a local study that included 369 children aged 6–15 years from pediatric clinics has reported a prevalence of HTN by 16.3% among girls and 14.4% among boys¹³. Additionally, El-Setouhy et al. reported a prevalence of HTN by 11.6% among 601 Saudi children aged 6–14 years³⁹. Comparing with other populations, prevalence of HTN among our study population is higher than the findings of several international studies. In an American study included 14,187 children and adolescents aged 3–18 years reported that 3.4% of participants had HTN⁴⁰. In Brazil, Martins et al. in a group of 1,549 adolescents aged 12–18 years (744 males), reported a prevalence of HTN by 10.5% in males and 9.9% in females⁴¹. An Indian study included 315 adolescents aged 14.31 ± 0.96 years (208 boys) reported that 5.4% of participants had HTN⁴². The discrepancy in local studies may be attributed from differences in age groups recruited as well as differences in methods to assess blood pressure. Cultural and ethnic differences may contribute to the discrepancies in studies done in other geographic regions.

Current research indicates that economic and nutritional transitions are taking place in numerous developing countries. In Saudi Arabia, there has been a notable rise in fast food consumption over recent decades, resulting in increased intake of energy, fats, and sodium⁴³. These changes in dietary habits and sedentary lifestyle among Saudi population have contributed to a higher prevalence of obesity and related health issues, including HTN⁴⁴. A previous local research has reported that behavioral factors largely account for the rise of HTN among Saudi adolescents, factors include obesity, physical inactivity, unhealthy eating habits, salt intake, energy drink consumption, and high fructose aerated beverages^11,45. Therefore, there is an urgent need for national awareness and interventional programs educating Saudi population, about the critical health consequences of HTN, and the significance of adopting healthy lifestyle behaviors including healthy eating and physical activity in preventing and controlling of HTN.

Our results did not find sex differences in the prevalence of HTN between boys and girl in our study, which is in line with the findings of previous studies^11,38. In contrast, other several studies reported sex differences in the prevalence of HTN. Some studies reported higher prevalence of HTN among boys than in girls^46,47. While other studies reported higher prevalence of HTN in girls than in boys⁴⁸. These discrepancies could be attributed to several factors, including the different methodologies employed to assess BP status, significant differences in sample sizes, as well as other physiological and environmental influences. Differences in the maturity status of participants (as indicated by Tanner stages), in addition to different sex hormone concentrations, fat store utilization, and effects on the X or Y chromosome, moreover, the increased sex hormone levels during the puberty stage among adolescents result in differences in fuel metabolism, body composition changes, lipid levels, and BP⁴⁹.

The present study found high prevalence of VDD, where 84.4% of adolescents had deficient VD levels. This was consistently demonstrated in previous local studies screening for VDD among Saudi children and adolescents^50,51. This emphasizes the urgent need for policy makers and healthcare authorities to conduct public health campaigns, intervention, and food fortification programs to address this persistent serious health problem. Recent studies in children and adolescents reported significantly low levels of VD in hypertensive children with normal BMI and authors suggested that VD may affect BP independently of obesity^52,53.

Several literatures have suggested that VD could play a role in HTN, owing to the presence of VD receptor in smooth muscles and endothelial cells of cardiomyocytes and blood vessels, which could reduce the oxidative stress, and inhibition of the renin‒angiotensin system, as well as modulation of endothelial function^26–28. Disagreeing with that, our results showed no differences in VD levels between hypertensive and normotensive adolescents, additionally, our data found only a weak inverse correlation between VD and SBP, and no correlation was found with DBP. This differential relationship supports existing evidence that VD status is mechanistically linked to HTN, particularly through its influence on arterial stiffness and the renin-angiotensin-aldosterone system (RAAS) (Fig. 4), which controls blood pressure and fluid balance. When vitamin D levels are low, renin production increases, leading to vasoconstriction and higher blood pressure. Furthermore, VD has direct effects on blood vessel function and inflammation, and is known to promotes healthy endothelial function via reduction of oxidative stress and insulin resistance, all of which contribute to maintaining normal vascular tone^26–28,54.

Fig. 4.

Mechanisms linking VDD to pediatric hypertension and dyslipidemia.

^26–28,54. The selective association with SBP suggests that VD’s antihypertensive effects may be predominantly mediated through its role in preserving arterial elasticity and mitigating the structural changes that contribute to increased pulse pressure, which is a major determinant of SBP. This is consistent with a body of research indicating that VDD promotes vascular smooth muscle hypertrophy and aortic stiffening^54,55. Given that isolated systolic HTN is a potent risk factor for adverse cardiovascular outcomes, our results highlight the potential clinical relevance of maintaining adequate VD levels as a strategy for mitigating this specific form of HTN and its associated risks^56,57. Clinically, the correction of VDD improved arterial stiffness was evident in meta-analysis⁵⁴, Elevated BP in adolescence is a strong predictor of adult HTN and cardiovascular risk⁵⁸, making our finding relevant despite intervention trials showing inconsistent BP-lowering effects of VD⁵⁹.

Our data did not show VDD as a significant risk factor for HTN. However, majority of our participants have deficient VD levels, which could impair the good proposed effects of VD in lowering BP, which could be confirmed in future interventional studies with VD supplementation in similar population of Saudi adolescents. Nevertheless, meta-analyses of VD supplementation have reported weak evidence to support an effect for VD in lowering BP⁵⁸. Furthermore, recent systematic analysis showed no effect of VD supplementation on SBP or DBP in randomized controlled trials (RCTs), and only a small decrease in DBP in non-randomized trials, and no effect was found for VD supplementation on cardiometabolic health in childhood and adolescence⁶⁰. Similar inconsistent findings were reported in adult population as well⁶¹. Further investigating the reason behind these mixed results through prospective cohort studies is warranted.

In parallel with the rising prevalence of VDD among the pediatric population, there has also been an increasing prevalence in other cardiometabolic risk factors, including changes in lipid profiles. The global prevalence of DLD in children and adolescents varies significantly, ranging from 6% to 65%, with the highest incidence noted in obese children⁶². Our results found high prevalence of DLD indices among our study population, where 22% of participants had hypertriglyceridemia, 55.5% had low–HDL–C levels, and 56.8% had high–LDL–C levels, which is higher than previous local studies. A previous Saudi study included 1,390 children aged 9–12 years has reported high prevalence of TC, LDL–C, and TG (32.7%, 33.1%, and 34.1%, respectively)⁶³. The prevalence of DLD among our Saudi adolescents is higher than that reported from other populations, e.g. in Spain (19.2%)⁶⁴ and Korea (19.7%)⁶⁵.

In the present study, HTN group had significantly higher serum levels of TG, TC, and LDL–C comparing to the non-HTN group, whereas HDL–C levels were significantly lower in the HTN group than in the non-HTN group. DLD could be linked to HTN through various mechanisms. Atherosclerosis, which arises from lipid abnormalities, can lead to structural alterations in large arteries, thereby diminishing their elasticity⁶⁶. Additionally, DLD can induce endothelial dysfunction, characterized by decreased production and activity of nitric oxide, along with abnormal vasomotor responses, potentially resulting in HTN (Fig. 4)⁶⁷. Moreover, the impairment of the renal microvasculature due to lipid abnormalities may also contribute to the development of HTN⁶⁸.

While we observed significant differences in lipid profile between hypertensive and normotensive participants (Table 2), our data did not show significant differences in lipid profile between participants with or without VDD (Table 3). A recent systematic review and meta-analysis of RCTs investigated efficiency of VD supplementation in improving DLD indices has found that VD correction was not effective in alleviating DLD, whether for a short or long duration, with a low or high dose, even if blood VD levels were significantly increased, that did not significantly affect HDL–C, LDL–C, or TC levels⁶⁹. Contrarily, several studies have indicated that sufficient serum VD levels were linked to an improved serum lipid profile, with the strongest evidence supporting a positive correlation between VD levels and HDL–C⁷⁰. These studies proposed that VD supplementation may be advantageous for children with DLD. However, the mechanisms underlying this relationship remain unclear, and it is essential to validate this correlation through well-constructed RCTs. Research has produced inconsistent findings regarding the connection between VD status and DLD, often suggesting a lack of significant effect despite improvements in VD levels. Furthermore, it has been suggested that the associations between VD and cardiometabolic health may not be causal⁷¹. The mechanisms through which VD affects the lipid profile are still unclear⁷². Given the conflicting evidence from both observational and interventional studies, it has been proposed that the relationship between VD and DLD may be influenced by obesity rather than indicating a direct causal link^70,71.

We found sex differences in the prevalence of lipid abnormalities, where hypertriglyceridemia was more prevalent among boys (24.4%) than in girls (20.7%), similarly for low–HDL–C levels, 61.8% in boys and 51.9% in girls. Conversely, the prevalence of high–LDL–C was higher in girls (60.4%) than in boys (50.3%). Comparing to other ethnicities, the observed sex differences are in line with the findings of the 2011–2014 National Health and Nutrition Examination Survey (NHANES), which reported that the prevalence of low–HDL–C was higher in boys (14.8%) than in girls (12.0%) and that high non-HDL–C levels were more common in girls (9.4%) than in boys (7.5%)⁷³. The similar trend of our findings with the NHANES study is potentially due to the adoption of a Western lifestyle among most of the Saudi population, which has a high-fat dense diet and sedentary behaviors⁷⁴. These sex differences are well established in previous large cohort studies, such as the German national survey study⁷⁵ and the Young Finns study⁷⁶, where higher levels of TC, LDL–C, and non-HDL–C were observed in girls after infancy than boys, which is maintained throughout childhood and adolescence and could be due to the impact of estrogen on lipid metabolism⁷⁷.

In light of the rising prevalence of DLD, VDD, obesity, and HTN, global and national policies have been implemented. Key strategies include pediatric dietary guidelines like the NCEP’s CHILD-1 and CHILD-2 diets, which limit saturated fat and cholesterol⁷⁸. Additionally, over 60 countries use front-of-pack nutrition labeling and taxes on unhealthy foods to promote better choices, “sin taxes” on sugar-sweetened beverages and unhealthy foods^79,80. Moreover, school-based interventions are common, with many countries improving meal quality and mandating physical activity^78,79. In Saudi Arabia, the Saudi authorities have adopted a comprehensive vision to combat these issues. Since 2017, the country has imposed taxes on unhealthy foods and made calorie and ingredient labeling mandatory. The Weqaya agency (https://www.pha.gov.sa/en-us/Pages/default.aspx), in coordination with the Saudi center for disease control (SCDC), also conducts periodic health screenings (including BMI, BP, and lipid tests) in schools since 2018⁸¹. In parallel, the Saudi Ministry of Health disseminates national guidelines targeting overweight/obesity (linking it to cardiovascular risk), hypertension diagnostics, including lipid profile screening, and clinical management protocols^82,83,84.

To our knowledge, this is the largest Saudi study screening for undiagnosed HTN and the first to investigate the interactions between HTN, VD, and DLD in Arab adolescents. Yet, the present study has some limitations. As a cross-sectional study, we cannot establish causality. Prospective studies are needed to validate our study findings. Factors affecting VD status, such as genetics, pubertal stage, physical activity, dietary intake, and socioeconomic differences, were also not assessed which may have affected the associations found. Additionally, the present findings should be applicable only to the Saudi adolescent population, as the economic, nutritional, and geographical differences in other ethnicities could influence the evaluated parameters in our study. Nevertheless, the present study is one of the few to investigate undiagnosed HTN in Arab populations. These findings can serve as a basis for larger epidemiological and longitudinal studies to validate the link between studied variables and pediatric HTN.

Conclusion

The present study revealed high prevalence of undiagnosed HTN, VDD, and DLD among Saudi adolescents. There were significant sex differences in HTN comorbidities and associated risk factors. Girls have worse VD status and lipid profiles, while boys have higher BP. Longitudinal studies to address the causes of undiagnosed HTN among Saudi adolescents are significant. The lack of significant association between HTN and VD in our study may need more prospective studies and well-structured RCTs for the evaluation of such relationship. Future research should focus on interventions in schools, targeted screening, or mechanistic dietary assessments.

Abbreviations

BMI

Body mass index

BP

Blood pressure

CVDs

Cardiovascular diseases

DLD

Dyslipidemia

HDL–C

High-density lipoprotein cholesterol

HTN

Hypertension

IOTF

International Obesity Task Force

LDL–C

Low-density lipoprotein cholesterol

NCEP

National Cholesterol Education Program

NHANES

National Health and Nutrition Examination Survey

non-HTN

Non-hypertension

OR

Odds ratio

SDs

Standard deviations

SPSS

Statistical Package for the Social Sciences

TC

Total cholesterol

TG

Triglycerides

T2DM

Type 2 Diabetes Mellitus

Author contributions

OEA: conceptualization, statistical analysis, writing original draft. MNKK: methodology. SS: review and editing. AA: investigations. AAlod and MA: supervision. NMA: Funding acquisition. All authors read and approved the final manuscript.

Funding

 The authors are thankful to the Ongoing Research Funding Program - Research Chairs (ORF-RC-2025-1400), King Saud University, Riyadh, Saudi Arabia, for funding this research.

Data availability

Data is provided within the manuscript.

Declarations

Competing interests

The authors declare no competing interests.

Ethical approval

This study was approved by the Institutional Review Board at College of Medicine, King Saud University, Riyadh, Saudi Arabia (No. E-19-4239, 29 October 2019). All procedures were conducted in compliance with the ethical standards of the Helsinki Declaration of 1964 and its most recent amendments.

Consent to participate

Written informed consent was obtained from the participants’ parents or legal guardian before inclusion in the study.