Baseline Characteristics of Study Participants
The study included 7,561 NHANES participants from 2005 to 2016, categorized into three groups based on APAR tertiles: Low (APAR ≤ 1.422), Moderate (1.422 < APAR ≤ 1.878), and High (APAR > 1.878). Table 1 revealed that participants in the high APAR group were more likely to be older and obese women, of Mexican ethnicity. Moreover, this group generally had lower levels of education and income, a higher propensity to smoke, and a greater prevalence of hypertension.
Relationships of APAR Levels with Mortality
During an average follow-up of 99.41 months, 1,021 deaths were recorded: 200 from cancer and 348 from CVD. Table 2 illustrated mortality distributions by APAR group for all-cause, cancer, and CVD mortality. Utilizing three Cox regression models, we established an independent association between APAR levels and mortality risk. Post-final multivariate adjustment (Model 3), hazard ratios (HRs) and 95% confidence intervals (CIs) for the low, moderate, and high APAR groups were, respectively, REF (reference), 1.03 (0.88-1.22), and 1.50 (1.28-1.75) for all-cause mortality (P < 0.001); REF, 0.87 (0.62-1.23), and 0.95 (0.67-1.34) for cancer mortality (P = 0.762); and REF, 1.07 (0.81-1.41), and 1.39 (1.06-1.82) for CVD mortality (P = 0.018) as shown in Table 3. The analysis confirmed a significant difference in all-cause and CVD mortality between the high and low APAR groups, indicating APAR's potential as an independent prognostic marker for all-cause and CVD mortality in the general population.
Table 2 The distributions of all-cause mortality, cancer mortality and CVD mortality across APAR tertiles
|
Total
|
Low
|
Moderate
|
High
|
|
|
N=7,561
|
n=2,531
|
n=2,516
|
n=2,514
|
P value
|
All-cause mortality
|
1021(13.5)
|
256(10.1)
|
321(12.8)
|
444(17.7)
|
<0.001
|
Cancer mortality
|
200(2.6)
|
63(2.5)
|
66(2.6)
|
71(2.8)
|
0.757
|
CVD mortality
|
348(4.6)
|
88(3.5)
|
115(4.6)
|
145(5.8)
|
0.001
|
Table 3 HRs (95% CIs) for mortality according to APAR levels
APAR group
|
Model 1 HR (95%CI)
|
P value
|
Model 2 HR (95%CI)
|
P value
|
Model 3 HR (95%CI)
|
P value
|
All-cause mortality
|
|
|
|
|
|
Low
|
REF
|
|
REF
|
|
REF
|
|
Moderate
|
1.21(1.03-1.43)
|
0.021
|
1.03(0.88-1.22)
|
0.685
|
1.03(0.88-1.22)
|
0.683
|
High
|
1.68(1.44-1.95)
|
<0.001
|
1.52(1.30-1.77)
|
<0.001
|
1.50(1.28-1.75)
|
<0.001
|
Cancer mortality
|
|
|
|
|
|
Low
|
REF
|
|
REF
|
|
REF
|
|
Moderate
|
1.01(0.72-1.43)
|
0.948
|
0.87(0.62-1.23)
|
0.431
|
0.87(0.62-1.23)
|
0.434
|
High
|
1.09(0.77-1.53)
|
0.629
|
0.97(0.69-1.37)
|
0.879
|
0.95(0.67-1.34)
|
0.762
|
CVD mortality
|
|
|
|
|
|
Low
|
REF
|
|
REF
|
|
REF
|
|
Moderate
|
1.26(0.96-1.67)
|
0.097
|
1.07(0.81-1.42)
|
0.623
|
1.07(0.81-1.41)
|
0.632
|
High
|
1.59(1.22-2.07)
|
0.001
|
1.44(1.10-1.88)
|
0.008
|
1.39(1.06-1.82)
|
0.018
|
Model 1: Non-adjusted
Model 2: Adjusted for age, sex, race
Model 3: Adjusted for age, sex, race, education level, annual family income, alcohol drinking, cigarette smoking, BMI, and history of hypertension
Detection of Nonlinear Relationships
Prior multivariate analysis indicated nonlinear relationships between APAR levels and mortality from all-cause and cancer, prompting further investigation. This identified L-shaped patterns, as depicted in Figure 1A for all-cause mortality and Figure 1B for cancer mortality, with inflection points at 1.289 and 2.167, respectively (Table 4). Below these thresholds, APAR levels were not significantly associated with mortality (HR 0.669; 95% CI 0.353-1.268 for all-cause and HR 0.792; 95% CI 0.549-1.142 for cancer). However, exceeding these thresholds resulted in a significant increase in adjusted HRs for mortality: 29.2% for all-cause and 38.3% for cancer, per 1-unit increase in APAR (HR 1.292; 95% CI 1.217-1.372 for all-cause and HR 1.383; 95% CI 1.199-1.596 for cancer).
Figure 1 Association between APAR levels and all-cause (A) and cancer mortality (B) in adults. Adjusted for age, sex, race, education level, annual family income, alcohol drinking, cigarette smoking, BMI, and history of hypertension. The solid and shadow represent the estimated values and their 95% CIs, respectively
Table 4 Threshold effect analysis of APAR levels on all-cause and cancer mortality
|
Adjusted HR, (95%CI), P-value
|
All-cause mortality
|
|
Fitting model by standard linear regression
|
1.343 (1.275-1.415) <0.001
|
Fitting model by two-piecewise linear regression
|
|
Inflection point
|
1.289
|
APAR < 1.289
|
0.669 (0.353-1.268) 0.218
|
APAR >= 1.289
|
1.292 (1.217-1.372) <0.001
|
Cancer mortality
|
|
Fitting model by standard linear regression
|
1.29 (1.131-1.472) <0.001
|
Fitting model by two-piecewise linear regression
|
|
Inflection point
|
2.167
|
APAR < 2.167
|
0.792 (0.549-1.142) 0.212
|
APAR >= 2.167
|
1.383 (1.199-1.596) <0.001
|
Adjusted for age, sex, race, education level, annual family income, alcohol drinking, cigarette smoking, BMI, and history of hypertension
Stratified Analysis
The survival benefit associated with higher APAR levels (≥ 1.289) compared to lower APAR levels (< 1.289) remained similar across diverse subgroups categorized by age, sex, race, history of hypertension, and BMI (Figure 2). No significant interaction was observed between serum APAR levels and the stratified variables. Furthermore, our results revealed a more pronounced positive association between APAR levels and all-cause mortality in male individuals, despite the non-significance of interaction tests.
Figure 2 Forest plots of stratified analyses of APAR levels and all-cause mortality. Age, sex, race, education level, annual family income, alcohol drinking, cigarette smoking, BMI, and history of hypertension were all adjusted except the variable itself