Abstract
The non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) is an emerging composite lipid measure. Current evidence regarding the association between NHHR and anxiety is limited. Understanding how changes in the NHHR may affect anxiety. The secondary objective of this study was to examine whether the association between NHHR and anxiety follows a nonlinear pattern. We conducted a cross-sectional study involving 15,242 participants with The National Health and Nutrition Examination Survey (NHANES). Anxiety was obtained from all participants. Logistic regression and smooth curve fitting were used to substantiate the research objective. The overall prevalence of anxiety disorders was 25.6%. The analysis revealed statistically significant differences in the prevalence of anxiety across the NHHR groups within the study population. Multivariate restricted cubic spline (RCS) regression demonstrated a J-shaped nonlinear relationship between NHHR and anxiety (P for nonlinearity < .05). The 2 variables exhibited a significant positive correlation, with the curve exhibiting a pronounced inflection point at NHHR values > 2.332. Furthermore, this relationship remained consistent across multiple subgroups stratified by sex, race, education level, marital status, body mass index (BMI), alcohol consumption, and smoking status. Using data from the NHANES (2007–2012), we investigated the association between NHHR levels and anxiety among adults in the United States. Analyses revealed a robust nonlinear J-shaped association. When the NHHR levels exceeded a threshold of 2.332, this relationship was associated with an increased risk of anxiety, highlighting its clinical relevance.
Keywords: anxiety, cross-sectional study, NHANES, NHHR, nonlinear curve relationship
1. Introduction
Anxiety is a global health concern with a prevalence that has risen steadily over recent decades,[1] affecting approximately 34% of the US population.[2] Characterized by intense, persistent feelings of worry and fear, anxiety profoundly affects individuals’ quality of life and overall functioning.[3] Therefore, the early recognition and prevention of anxiety symptoms are therefore crucial.
Current investigations into the link between psychological health and lipid metabolism have highlighted the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (non-HDL-C/HDL-C), termed NHHR, as a promising new biomarker. Regarding NHHR’s components, low-density lipoprotein cholesterol (LDL-C) generally constitutes 50% to 70% of non-HDL-C. Conversely, HDL-C, recognized for its protective properties, facilitates reverse transport and removal of surplus cholesterol from tissues.[4] As a recently introduced lipid ratio useful for assessing atherosclerotic lipid profiles, NHHR has attracted considerable interest beacause of its role in modulating conditions including diabetes,[4] hypertension,[5] osteoporosis,[6] and hyperuricemia.[7] Previous observational studies demonstrated a relationship between serum lipid levels and anxiety disorders. A recent animal experiment[8] indicated that high-fat diet administration for 8 weeks induced hyperlipidemia in mice, accompanied by anxiety-like behaviors. Complementing this, a 2021 clinical study[9] demonstrated that interventions targeting triglyceride metabolism effectively alleviate anxiety symptoms. Consequently, examining the connection between NHHR and anxiety could yield significant insights at the crossroads of lipid metabolism and mental well-being, motivating deeper research into preventative approaches and therapeutic interventions.
2. Materials and methods
2.1. Study population
The NHANES is a comprehensive research program designed to assess the health and nutritional status of adults and children across the United States. All study procedures were approved by the Ethics Review Board of the National Center for Health Statistics before data collection, and all participants signed informed consent forms. Visit https://www.cdc.gov/nchs/nhanes/ for details of the process.[10]
This cross-sectional study utilized data from 3 NHANES cycles conducted between 2007 and 2012. The initial sample included 30,442 participants; however, exclusion criteria were applied to refine the study population. Participants were excluded if they were under 18 years of age, had incomplete data on key variables such as anxiety or NHHR; or lacked information on critical covariates, including age, sex, race, education level, marital status, poverty income ratio (PIR), BMI, smoking status, alcohol consumption, physical activity, hypertension, diabetes, depression, and sedative-hypnotic drugs. After applying these criteria, the final sample comprised 15,242 participants (see Fig. 1). In this study, we excluded individuals under 18 years of age, individuals with missing anxiety data and missing NHHR data, and individuals missing data on key covariates; a detailed flowchart of this process is provided in Figure 1.
Figure 1.
Study’s flow diagram. HDL = high-density lipoprotein.
2.2. Non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR)
The calculation formula for NHHR is: NHHR = Non-HDL-C/HDL-C.
2.3. Anxiety
Anxiety in the NHANES 2007–2012 study was assessed using a self-report question: “During the past 30 days, for about how many days have you felt worried, tense, or anxious?” Detailed information on this anxiety measure is available on the NHANES website (https://wwwn.cdc.gov/Nchs/Nhanes/2007-2008/HSQ_E.htm). Consistent with previous studies,[11-13] anxiety status was classified as “no” (felt anxious for 0–6 d/mo) or “yes” (felt anxious for 7–30 d/mo).
2.4. Covariates
Covariate data were meticulously gathered and segmented by diverse demographic factors such as sex (female and male), age (in years), race/ethnicity (Mexican American, other Hispanic, non-Hispanic White, non-Hispanic Black, other races), educational attainment (high school or above, less than high school), marital status (married, separated/divorced/widowed, never married), and PIR classified into ≤1.3, 1.3–3.5, and >3.5. Participants’ smoking and drinking behaviors were categorized as never, former, and current based on their responses to self-administered questionnaires. In terms of alcohol consumption, never drinkers had ingested fewer than 12 alcoholic beverages in their lifetime, former drinkers had consumed at least 12 drinks but had abstained in the past year, and current drinkers had consumed at least 12 drinks and had alcohol intake within the previous year.[14] BMI was divided into 3 groups (BMI < 25, 25 ≤ BMI < 30, and BMI ≥ 30).[15] Blood pressure readings were obtained up to four consecutive times by trained professionals, with an average of a minimum of 3 measurements determining both systolic blood pressure (SBP) and diastolic blood pressure (DBP). Diabetes status was established based on whether participants had been previously diagnosed, were currently using insulin, or were taking other diabetes-related medications.[16] Depressive symptoms were evaluated using the Patient Health Questionnaire-9 (PHQ-9), with scores of 10 or above indicating depression.[17]
2.5. Statistical analysis
Normality assessment of variable distributions was conducted using histograms, Q–Q plots, and where appropriate, Kolmogorov–Smirnov tests. Normally distributed continuous variables are expressed as mean (SD), non-normally distributed variables as median (IQR), and categorical variables as n (%).
Continuous variables were compared using Student t test for normally distributed data and the Mann–Whitney U test for non-normally distributed variables. Categorical variables were analyzed using either χ2 test or Fisher exact test, as appropriate.
The association between NHHR and anxiety was evaluated using binary logistic regression and expressed as odds ratios (ORs) with 95% confidence intervals (CIs). The models were adjusted for clinically pertinent covariates selected from prior evidence. NHHR was modeled as a categorical variable (divided into 5 quantiles). Three hierarchical models are constructed:
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Model 1: Age, sex, race;
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Model 2: Age, sex, race, PIR, marital status, education level;
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Model 3: Age, sex, race, PIR, marital status, education level, smoking status, alcohol consumption, hypertension, diabetes, hyperlipidemia.
Restricted cubic splines were applied to model potential nonlinear dose–response relationships between NHHR and anxiety, with NHHR analyzed as a continuous variable. Four knots were chosen as the optimal balance between model flexibility and stability, given our sample size (n = 15,242); we placed knots at the fifth, 35th, 65th, and 95th percentiles of the NHHR distribution.
Based on the smoothing curve analysis, a 2-piecewise linear regression model detected significant threshold effects with adjustments for relevant confounders. Subgroup analyses were performed to evaluate the potential effect modification by sex, race, PIR, education level, marital status, BMI, alcohol status, and smoking status. Missing data (<5% overall) were handled using listwise deletion. To ensure comparability, all analyses were repeated using the complete case dataset. Sensitivity analyses were used to evaluate the robustness of the findings across alternative models. The effect sizes and P-values were computed and reported for all models, and the findings were compared across the models.
Analyses were performed using R Statistical Software (v4.2.2; R Foundation for Statistical Computing, Vienna, Austria, https://www.R-project.org/) and the Free Statistics platform (v2.2; Beijing, China, http://www.clinicalscientists.cn/freestatistics), which implements R’s statistical engine via Python-based Graphical User Interface (GUI) for reproducible analysis. Statistical significance was defined as a 2-sided P < .05.
3. Results
3.1. Baseline characteristics of participants
Table 1 presents the baseline characteristics of the participants stratified by NHHR quintiles. The study included 15,242 participants, of whom 25.6% reported anxiety disorders. The mean age was 48.3 years, and 50.1% were male. Significant variations in demographic, anthropometric, socioeconomic, lifestyle, and health-status characteristics were observed across the NHHR quintiles.
Table 1.
Baseline characteristics of participants.
| Variables | Total (n = 15,242) | Q1 (n = 3049) | Q2 (n = 3045) | Q3 (n = 3047) | Q4 (n = 3046) | Q5 (n = 3055) | P |
|---|---|---|---|---|---|---|---|
| Sex, n (%) | <.001 | ||||||
| Male | 7643 (50.1) | 1135 (37.2) | 1264 (41.5) | 1488 (48.8) | 1753 (57.6) | 2003 (65.6) | |
| Female | 7599 (49.9) | 1914 (62.8) | 1781 (58.5) | 1559 (51.2) | 1293 (42.4) | 1052 (34.4) | |
| Age, yr | 48.3 ± 18.6 | 46.6 ± 20.7 | 48.5 ± 19.8 | 49.2 ± 18.9 | 48.6 ± 17.3 | 48.6 ± 15.9 | <.001 |
| Race/ethnicity, n (%) | <.001 | ||||||
| Mexican American | 2419 (15.9) | 337 (11.1) | 435 (14.3) | 464 (15.2) | 579 (19) | 604 (19.8) | |
| Other Hispanic | 1624 (10.7) | 256 (8.4) | 297 (9.8) | 311 (10.2) | 378 (12.4) | 382 (12.5) | |
| Non-Hispanic White | 6857 (45.0) | 1331 (43.7) | 1362 (44.7) | 1381 (45.3) | 1343 (44.1) | 1440 (47.1) | |
| Non-Hispanic Black | 3142 (20.6) | 848 (27.8) | 679 (22.3) | 655 (21.5) | 537 (17.6) | 423 (13.8) | |
| Other race | 1200 (7.9) | 277 (9.1) | 272 (8.9) | 236 (7.7) | 209 (6.9) | 206 (6.7) | |
| WC, cm | 98.7 ± 16.4 | 89.6 ± 15.1 | 95.2 ± 16.0 | 99.6 ± 15.6 | 103.5 ± 15.4 | 105.6 ± 14.8 | <.001 |
| BMI, n (%) | <.001 | ||||||
| ≤25 kg/m2 | 4599 (30.2) | 1646 (54) | 1174 (38.6) | 820 (26.9) | 551 (18.1) | 408 (13.4) | |
| 25–30 kg/m2 | 5093 (33.4) | 836 (27.4) | 973 (32) | 1087 (35.7) | 1085 (35.6) | 1112 (36.4) | |
| >30 kg/m2 | 5550 (36.4) | 567 (18.6) | 898 (29.5) | 1140 (37.4) | 1410 (46.3) | 1535 (50.2) | |
| Family PIR, n (%) | <.001 | ||||||
| Low (≤1.3) | 5147 (33.8) | 976 (32) | 960 (31.5) | 1009 (33.1) | 1026 (33.7) | 1176 (38.5) | |
| Medium (1.3–3.5) | 5580 (36.6) | 1092 (35.8) | 1123 (36.9) | 1114 (36.6) | 1133 (37.2) | 1118 (36.6) | |
| High (>3.5) | 4515 (29.6) | 981 (32.2) | 962 (31.6) | 924 (30.3) | 887 (29.1) | 761 (24.9) | |
| Education level, n (%) | <.001 | ||||||
| Less than high school | 7606 (50.0) | 1280 (42.1) | 1450 (47.8) | 1513 (49.7) | 1626 (53.4) | 1737 (57) | |
| High school or above | 7603 (50.0) | 1759 (57.9) | 1584 (52.2) | 1533 (50.3) | 1417 (46.6) | 1310 (43) | |
| Marital status, n (%) | <.001 | ||||||
| Married/living with partner | 8947 (58.8) | 1560 (51.3) | 1716 (56.4) | 1826 (59.9) | 1895 (62.2) | 1950 (63.9) | |
| Separated/divorced/widowed | 3520 (23.1) | 763 (25.1) | 721 (23.7) | 689 (22.6) | 669 (22) | 678 (22.2) | |
| Never married | 2759 (18.1) | 716 (23.6) | 604 (19.9) | 532 (17.5) | 481 (15.8) | 426 (13.9) | |
| Alcohol status, n (%) | <.001 | ||||||
| Current or ever | 11,029 (72.4) | 2227 (73.1) | 2152 (70.7) | 2141 (70.3) | 2198 (72.2) | 2311 (75.7) | |
| Never | 4200 (27.6) | 818 (26.9) | 890 (29.3) | 904 (29.7) | 845 (27.8) | 743 (24.3) | |
| Smoking status, n (%) | <.001 | ||||||
| Current or ever | 5434 (35.9) | 1123 (37) | 1034 (34.2) | 1001 (33.1) | 1011 (33.3) | 1265 (41.6) | |
| Never | 9721 (64.1) | 1909 (63) | 1992 (65.8) | 2022 (66.9) | 2022 (66.7) | 1776 (58.4) | |
| Diabetes, n (%) | .112 | ||||||
| Yes | 1803 (12.1) | 335 (11.1) | 348 (11.6) | 359 (12.1) | 363 (12.2) | 398 (13.3) | |
| No | 13,132 (87.9) | 2670 (88.9) | 2642 (88.4) | 2618 (87.9) | 2616 (87.8) | 2586 (86.7) | |
| Hypertension, n (%) | <.001 | ||||||
| Yes | 5257 (34.5) | 958 (31.5) | 1007 (33.1) | 1058 (34.8) | 1097 (36.1) | 1137 (37.3) | |
| No | 9964 (65.5) | 2088 (68.5) | 2035 (66.9) | 1986 (65.2) | 1943 (63.9) | 1912 (62.7) | |
| Hyperlipidemia, n (%) | <.001 | ||||||
| Yes | 5507 (36.4) | 800 (26.4) | 957 (31.7) | 1063 (35.2) | 1224 (40.4) | 1463 (48.3) | |
| No | 9619 (63.6) | 2230 (73.6) | 2065 (68.3) | 1958 (64.8) | 1802 (59.6) | 1564 (51.7) | |
| Depression, n (%) | <.001 | ||||||
| Yes | 1482 (9.7) | 258 (8.5) | 259 (8.5) | 288 (9.5) | 309 (10.1) | 368 (12) | |
| No | 13,760 (90.3) | 2791 (91.5) | 2786 (91.5) | 2759 (90.5) | 2737 (89.9) | 2687 (88) | |
| Anxiety, n (%) | .004 | ||||||
| Yes | 3900 (25.6) | 771 (25.3) | 742 (24.4) | 750 (24.6) | 775 (25.4) | 862 (28.2) | |
| No | 11,342 (74.4) | 2278 (74.7) | 2303 (75.6) | 2297 (75.4) | 2271 (74.6) | 2193 (71.8) |
BMI = body mass index, PIR = poverty income ratio, WC = waist circumference.
3.2. Association of NHHR and anxiety
Table 2 shows the relationship between the NHHR and anxiety. In the continuous model, after full adjustment for covariates, NHHR was found to be significantly associated with anxiety (OR = 1.05, 95% CI: 1.02–1.08, P < .001), with a 5% increase in the prevalence of anxiety. After full adjustment for covariates, participants in the highest NHHR quintile (Q5) continued to exhibit a significantly increased likelihood of anxiety compared with those in the lowest quintile (OR = 1.22, 95% CI: 1.08–1.38, P = .002). The odds ratios for Q2, Q3, and Q4 were not statistically significant in this fully adjusted model. Overall, a significant dose-response relationship was observed with increasing NHHR quintiles.
Table 2.
Association between NHHR and anxiety.
| Variable | n | Model 1 | Model 2 | Model 3 | |||
|---|---|---|---|---|---|---|---|
| OR (95% CI) | P value | OR (95% CI) | P value | OR (95% CI) | P value | ||
| NHHR | 15,242 | 1.08 (1.05–1.11) | <.001 | 1.07 (1.04–1.10) | <.001 | 1.05 (1.02–1.08) | <.001 |
| NHHR in 5 groups | |||||||
| Q1 | 3049 | 1 (Ref) | 1 (Ref) | 1 (Ref) | |||
| Q2 | 3045 | 0.98 (0.87–1.11) | .779 | 0.99 (0.88–1.12) | .914 | 0.99 (0.87–1.11) | .828 |
| Q3 | 3047 | 1.04 (0.92–1.17) | .511 | 1.04 (0.93–1.18) | .472 | 1.03 (0.91–1.17) | .598 |
| Q4 | 3046 | 1.13 (1.01–1.28) | .037 | 1.13 (1–1.28) | .043 | 1.10 (0.97–1.24) | .133 |
| Q5 | 3055 | 1.36 (1.21–1.53) | <.001 | 1.32 (1.17–1.49) | <.001 | 1.22 (1.08–1.38) | .002 |
| Trend.test | <.001 | <.001 | <.001 | ||||
Model 1: age, sex, race.
Model 2: age, sex, race, PIR, marital status, education level.
Model 3: age, sex, race, PIR, marital status, education level, smoking status, alcohol consumption, hypertension, diabetes, hyperlipidemia.
CI = confidence interval, NHHR = non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio, OR = odds ratio, PIR = poverty income ratio.
3.3. The nonlinear association between NHHR and anxiety
Figure 2 illustrates the RCS analysis examining the association between NHHR and anxiety adjusted for the covariates defined in model 3. A statistically significant nonlinear relationship was demonstrated between NHHR and anxiety levels (P for nonlinearity < .05).
Figure 2.
A nonlinear association between NHHR and anxiety. NHHR = non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio.
3.4. Threshold effect analysis
Nonlinearity between NHHR and anxiety disorders was assessed using a threshold effect analysis (Table 3). A significant inflection point emerged at NHHR = 2.332 (likelihood ratio test, P = .034). Threshold Effect Analysis with Multiplicity Adjustment, Significant after correction (Bonferroni P = .0198, FDR q-value = 0.013). Below this threshold (NHHR < 2.332), NHHR was not significantly associated with anxiety (OR = 0.89; 95% CI: 0.76–1.04; P = .14). Above the inflection point (NHHR ≥ 2.332), each unit increase in NHHR corresponded to a 5.9% higher likelihood of anxiety (OR = 1.06; 95% CI: 1.01–1.11; P = .01).
Table 3.
Threshold effect analysis of NHHR-anxiety association with multiplicity adjustment.
| NHHR | No. | Adjusted model | |||
|---|---|---|---|---|---|
| OR (95% CI) | P-value | Bonferroni P | FDR q-value | ||
| <2.332 | 5509 | 0.889 (0.759–1.041) | .1439 | 0.2878 | 0.192 |
| ≥2.332 | 9225 | 1.059 (1.014–1.105) | .0099 | 0.0198 | 0.013 |
| Likelihood ratio test | – | – | .034 | – | – |
CI = confidence interval, FDR = false discovery rate, NHHR = non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio, OR = odds ratio.
3.5. Subgroup analysis
The subgroup analysis results presented in Figure 3 indicate no statistically significant interactions between NHHR and anxiety across multiple demographic and lifestyle factors including sex, race, PIR, education level, marital status, BMI, alcohol status, and smoking status. However, a significant interaction effect was observed in the subgroup with a PIR ≤ 1.3. The association between NHHR and anxiety remained robust across all subgroups.
Figure 3.
Association between in NHHR and anxiety subgroup analyses based on sex, race, PIR, education level, marital status, BMI, alcohol status and smoking status. BMI = body mass index, CI = confidence interval, NHHR = non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio, OR = odds ratio, PIR = poverty income ratio.
4. Discussion
This cross-sectional study examined the association between NHHR and anxiety prevalence in adults in the United States. A nonlinear relationship was identified, revealing that NHHR levels exceeding the optimal inflection point (NHHR = 2.332) demonstrated significantly elevated anxiety risk after adjustment for sociodemographic factors, lifestyle behaviors, and health status. These positive associations persisted across subgroups stratified by sex, race, education, marital status, BMI, alcohol consumption, and smoking status.
A PIR threshold of 1.3 demarcates near-poverty conditions in the United States. Individuals below this threshold face heightened financial stress, which may exacerbate biological pathways linking dyslipidemia to anxiety – such as chronic inflammation, hypothalamic–pituitary–adrenal axis dysregulation, and limited access to healthcare. For the economic stability domain, low levels of household income are associated with lifetime mental health disorders, and a reduction in household income is associated with an increased risk for mental health disorders.[18] Similarly, a US adult cross-sectional study reported lower income levels correlated with a 36% higher risk of anxiety disorders in adults.[19]
NHHR, which considers both the risk factor (non-HDL-C) and the protective factor (HDL-C) in atherosclerosis, has emerged as a new lipid metabolism marker.[20] An increasing amount of research indicates that NHHR is a more potent predictor of the risk for diseases associated with lipids,[21,22] including its superiority over traditional lipid parameters in assessing the extent of atherosclerosis.[23] Although the role of NHHR in anxiety has not been previously studied, the association between HDL-C levels and anxiety has been explored. A Survey of Patients with Generalized anxiety Disorder in Outpatient Clinics suggests that there is an association between the different types of anhedonia (trait consummatory and state anhedonia) and low cholesterol, HDL or triglyceride levels in patients presenting with mood or anxiety disorders.[24] A cross-sectional study in Greece showed that HDL-C level was negatively associated with depression and anxiety symptoms.[25] Recently, a large prospective study showed an association between low HDL-C levels and the risk of depression, anxiety, and stress-related disorders during 6.7 years follow-up.[26]
A community-based prospective cohort study conducted in the United Kingdom demonstrated that an elevated TG/HDL-C ratio, serving as an alternative to the triglyceride-glucose (TyG) index, may predict increased risk of anxiety.[27] Recent studies have also suggested significant associations between NHHR and depression symptoms,[28] sleep disorders[15] and suicidal ideation.[29] The secondary messenger system of the brain relies heavily on cholesterol, which is closely linked to the actions of mood stabilizers and antidepressants.[30] Depressive and anxiety disorders are defined according to the current diagnostic systems, accounting for a number of key symptoms, but these symptoms are more or less pathognomonic and are common across psychiatric and physical illnesses.[31] For instance, depression and anxiety exhibit significant clinical overlap, and their symptoms are frequently inseparable.[32] In summary, the conclusions of these studies indirectly support our findings.
Longitudinal data indicate heterogeneous temporal dynamics between mental health disorders and dyslipidemia, with association directionality differing across investigations.
A Dutch prospective cohort (2-year follow-up) demonstrated that initial depressive or anxious manifestations predicted subsequent HDL-cholesterol reductions and increased waist circumference, explicitly refuting reverse causality.[33] Conversely, analysis of Sweden’s AMORIS cohort (n = 2,11,200; median 21-year follow-up) established significant associations between elevated triglyceride levels, diminished HDL-cholesterol, and subsequent anxiety disorder diagnoses.[34]Collectively, these findings suggest bidirectional anxiety-dyslipidemia interplay. Whilst certain longitudinal studies support dyslipidemia preceding anxiety onset – consistent with unidirectional models – the presence of opposing evidence precludes causal certainty, and we cannot rule out reverse causation.
The use of a large, nationally representative sample of US adults is a significant strength of this study. Consequently, we conducted a comprehensive adjustment for a range of variables to enhance the reliability and validity of our findings. Our study has several limitations. First, owing to the intrinsic nature of cross-sectional study designs, the ability to thoroughly investigate causal relationships is limited. Second, this outcome measure assessed anxiety symptoms rather than clinically diagnosed anxiety disorders, with the self-report mechanism introducing inherent limitations due to its subjective nature. Furthermore, while we adjusted for certain covariates, it was not possible to account for all potential factors, and uncontrolled variables could still have impacted our conclusions. Finally, although the NHANES cohort comprised participants from various ethnic and socioeconomic backgrounds, it is important to note that all the participants were from the United States. Consequently, our findings require validation in populations from other countries, particularly those in low-to middle-income nations. Additionally, we used the 2007–2012 NHANES data, which are old and may have biases due to changes in mental health data collection and reporting over time. We chose this dataset based on other studies’ practices and its unique anxiety-related data; however, more recent data would be better.
5. Conclusions
Using data from the NHANES (2007–2012), we investigated the association between NHHR levels and anxiety among adults in the United States. Analyses revealed a robust nonlinear J-shaped association. When the NHHR levels exceeded a threshold of 2.332, this relationship was associated with an increased risk of anxiety, highlighting its clinical relevance.
Acknowledgments
To all who participated in NHANES and lent a hand, our heartfelt gratitude.
Author contributions
Conceptualization: Yingzi Zhang.
Data curation: Libin Song.
Formal analysis: Yu Xu.
Funding acquisition: Yingzi Zhang.
Investigation: Libin Song, Yu Xu.
Methodology: Libin Song.
Project administration: Yingzi Zhang.
Resources: Yu Xu.
Validation: Yingzi Zhang.
Writing – original draft: Libin Song, Yu Xu.
Writing – review & editing: Yingzi Zhang.
Abbreviations:
- BMI
- body mass index
- CI
- confidence interval
- DBP
- diastolic blood pressure
- HDL-C
- high-density lipoprotein cholesterol
- LDL-C
- low-density lipoprotein cholesterol
- NHANES
- National Health and Nutrition Examination Survey
- NHHR
- non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio
- Non-HDL-C
- non-high-density lipoprotein cholesterol
- OR
- odds ratio
- PHQ-9
- Patient Health Questionnaire-9
- PIR
- poverty income ratio
- RCS
- restricted cubic splines
- SBP
- systolic blood pressure
- TG
- triglyceride
- TyG
- triglyceride-glucose index.
This study was supported by the Quzhou Municipal Science and Technology Bureau (Item No. 2024ZD068).
The investigation was approved by the NCHS Ethics Review Board, and participants were required to provide signed consent.
The authors have no conflicts of interest to disclose.
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
How to cite this article: Song L, Xu Y, Zhang Y. A nonlinear curve relating non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) to anxiety in American adults: A cross-sectional study. Medicine 2026;105:16(e48453).
Contributor Information
Libin Song, Email: slb1052@163.com.
Yu Xu, Email: zjqzxuy@163.com.
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