Relationship Between Plasma Aldosterone Concentrations and Non-Alcoholic Fatty Liver Disease Diagnosis in Patients with Hypertension: A Retrospective Cohort Study

Figures & data

Figure 1 Flow chart of study participant selection.

Table 1 Baseline Characteristics of the Study Participants According to Plasma Aldosterone Concentrations Categories

Variable	Total	PAC			P-value
		Tertile 1	Tertile 2	Tertile 3
		≤11.55 ng/dL	11.56–16.39 ng/dL	≥16.40 ng/dL
No. of participants	3713	1235	1235	1243
Male, %	1922 (51.76%)	623 (50.45%)	657 (53.20%)	642 (51.65%)	0.390
Age, yr	52.00 ± 11.80	52.16 ± 11.84	51.82 ± 11.75	52.03 ± 11.82	0.764
BMI, kg/m2	24.71 ± 2.47	23.16 ± 2.52	24.91 ± 1.45	26.05 ± 2.37	<0.001
DBP, mmHg	87.96 ± 14.43	87.24 ± 14.87	88.63 ± 14.13	88.02 ± 14.25	0.058
SBP, mmHg	144.16 ± 20.71	143.70±20.81	144.62± 0.56	144.16±20.78	0.540
Current smoker, %	492 (13.25%)	113 (9.15%)	181 (14.66%)	198 (15.93%)	<0.001
Diabetes, %	912 (24.56%)	266 (22.17%)	302 (25.08%)	281 (23.36%)	0.054
PA, %	154 (4.15%)	42 (3.40%)	53 (4.29%)	59 (4.75%)	0.232
TC, mmol/L	4.50 ± 0.96	4.50 ± 0.96	4.49 ± 0.93	4.52 ± 0.97	0.750
TG, mmol/L	1.55 (1.10–2.20)	1.51 (1.09–2.20)	1.58 (1.11–2.21)	1.57 (1.12–2.20)	0.691
HDL-C, mmol/L	1.04 ± 0.25	1.05 ± 0.25	1.05 ± 0.26	1.03 ± 0.24	0.051
LDL-C, mmol/L	2.71 ± 0.82	2.69 ± 0.81	2.69 ± 0.81	2.74 ± 0.85	0.214
FBG, mmol/L	5.13 ± 1.70	5.22 ± 1.86	5.09 ± 1.77	5.07 ± 1.46	0.068
ALT, U/L	23.00 (15.00–35.05)	22.00 (14.04–33.00)	23.00 (15.00–36.12)	24.00 (16.00–36.35)	<0.001
AST, U/L	19.00 (15.00–24.79)	19.00 (15.00–24.00)	19.00 (15.63–25.00)	19.00 (15.00–25.00)	0.360
GGT, U/L	29.00 (18.00–45.38)	28.00 (18.00–43.79)	29.55 (18.00–46.39)	29.00 (18.00–46.42)	0.244
Cr, umol/L	67.31 ± 18.10	65.63 ± 16.82	66.87 ± 17.04	69.41 ± 20.08	<0.001
BUN, mmol/L	5.46 ± 2.02	5.51 ± 2.04	5.36 ± 1.95	5.51 ± 2.07	0.118
UA, umol/L	343.13 ± 96.08	332.96 ± 92.49	345.57 ± 96.28	350.82 ± 98.56	<0.001
Medications use
Lipid-lowering drugs, %	1939 (52.22%)	628 (50.85%)	672 (54.41%)	639 (51.41%)	0.162
Antiplatelet agents, %	2273 (61.22%)	751 (60.81%)	749 (60.65%)	773 (62.19%)	0.688
Insulin, %	255 (6.87%)	107 (8.66%)	85 (6.88%)	63 (5.07%)	0.002
Oral antidiabetic agents, %	566 (15.24%)	204 (16.52%)	172 (13.93%)	190 (15.29%)	0.201
β-blockers, %	1227 (33.05%)	397 (32.15%)	417 (33.77%)	413 (33.23%)	0.684
CCB, %	2783 (74.95%)	933 (75.55%)	910 (73.68%)	940 (75.62%)	0.452
ACEI/ARB, %	2391 (64.40%)	780 (63.16%)	799 (64.70%)	812 (65.33%)	0.511
Spironolactone, %	667 (17.96%)	215 (17.41%)	256 (20.73%)	196 (15.77%)	0.005

Notes: Data are mean (standard deviation), n (%), or median (interquartile range).

Abbreviations: BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; TC, total cholesterol; TG, triglyceride; HDL-c, high-density lipoprotein cholesterol; LDL-c, low-density lipoprotein cholesterol; FPG, fasting plasma glucose; ALT, alanine transaminase; AST, aspartate transaminase; GGT, gamma-glutamyl transferase; Cr, creatinine; BUN, blood urea nitrogen; UA, uric acid; CCB, calcium channel blockers; ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; PAC, plasma aldosterone concentration; PA, primary aldosteronism.

Figure 2 Cumulative hazards of the risk of new-onset NAFLD according to the tertiles of the PAC.

Table 2 Regression Models of Effects of PAC on New-Onset NAFLD

Exposure	Incidence Rate (Per 100 Person-Years)	Crude Model		Adjusted Model 1		Adjusted Model 2		Adjusted Model 3
		HR (95% CI)	P-value	HR (95% CI)	P-value	HR (95% CI)	P-value	HR (95% CI)	P-value
Per 1 ng/dL increment		1.04 (1.03, 1.05)	< 0.001	1.05 (1.04, 1.06)	< 0.001	1.04 (1.04, 1.05)	< 0.001	1.04 (1.04, 1.05)	< 0.001
Per 5 ng/dL increment		1.21 (1.18, 1.25)	< 0.001	1.27 (1.22, 1.31)	< 0.001	1.24 (1.20, 1.29)	< 0.001	1.24 (1.19, 1.29)	< 0.001
Tertiles
T1	10.29 (9.31, 11.33)	Reference		Reference		Reference		Reference
T2	9.93 (8.98, 10.97)	0.97 (0.85, 1.12)	0.678	1.02 (0.88, 1.18)	0.823	1.02 (0.87, 1.20)	0.810	1.02 (0.87, 1.20)	0.765
T3	17.59 (16.72, 18.49)	1.67 (1.48, 1.88)	< 0.001	1.79 (1.56, 2.05)	< 0.001	1.72 (1.49, 1.99)	< 0.001	1.71 (1.47, 1.98)	< 0.001
P for trend		< 0.001		< 0.001		< 0.001		< 0.001

Notes: Crude model adjusted for none. Model 1 adjusted for age and sex. Model 2 adjusted for the variables in Model 1 plus BMI, current smoker, SBP, DBP, diabetes, PA, TG, TC, HDL-c, LDL-C, GGT, ALT, AST, BUN, Cr, UA, FPG. Model 3 adjusted for the variables in Model 2 plus lipid-lowering drugs, insulin, oral antidiabetic agents, β-blockers, CCB, antiplatelet agents, ACEI/ARB, spironolactone.

Abbreviations: CI, confidence interval; HR, hazard ratio; NAFLD, non-alcoholic fatty liver disease; BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; TC, total cholesterol; TG, triglyceride; HDL-c, high-density lipoprotein cholesterol; LDL-c, low-density lipoprotein cholesterol; FPG, fasting plasma glucose; ALT, alanine transaminase; AST, aspartate transaminase; GGT, gamma-glutamyl transferase; Cr, creatinine; BUN, blood urea nitrogen; UA, uric acid; CCB, calcium channel blockers; ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; PAC, plasma aldosterone concentration; PA, primary aldosteronism.

Table 3 Threshold Effect Analyses of PAC (per 5 Ng/dL Increase) on the Risk of New-Onset NAFLD Using Two-Piecewise Regression Models

The Inflection Point of PAC	Crude Model		Adjusted Model 1		Adjusted Model 2		Adjusted Model 3
	HR (95% CI)	P-value	HR (95% CI)	P-value	HR (95% CI)	P-value	HR (95% CI)	P-value
Model I
Per 5 ng/dL increment	1.21 (1.18, 1.25)	< 0.001	1.27 (1.22, 1.31)	< 0.001	1.24 (1.20, 1.29)	< 0.001	1.24 (1.19, 1.29)	< 0.001
Model II
< 13 ng/dL (per 5 ng/dL increment)	0.94 (0.80, 1.10)	0.434	1.00 (0.84, 1.19)	0.983	0.98 (0.82, 1.16)	0.804	0.98 (0.82, 1.17)	0.832
≥ 13 ng/dL (per 5 ng/dL increment)	1.26 (1.21, 1.31)	< 0.001	1.31 (1.25, 1.36)	< 0.001	1.31 (1.25, 1.36)	< 0.001	1.30 (1.25, 1.35)	< 0.001
P for log-likelihood ratio test	0.002		0.008		0.004		0.005

Notes: Crude model adjusted for none. Model 1 adjusted for age and sex. Model 2 adjusted for the variables in Model 1 plus BMI, current smoker, SBP, DBP, diabetes, PA, TG, TC, HDL-c, LDL-C, GGT, ALT, AST, BUN, Cr, UA, FPG. Model 3 adjusted for the variables in Model 2 plus lipid-lowering drugs, insulin, oral antidiabetic agents, β-blockers, CCB, antiplatelet agents, ACEI/ARB, spironolactone. Model I, linear analysis; Model II, non-linear analysis. P for log-likelihood ratio test < 0.05 means Model II is significantly different from Model I, which indicates a non-linear relationship.

Abbreviations: CI, confidence interval; HR, hazard ratio; NAFLD, non-alcoholic fatty liver disease; BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; TC, total cholesterol; TG, triglyceride; HDL-c, high-density lipoprotein cholesterol; LDL-c, low-density lipoprotein cholesterol; FPG, fasting plasma glucose; ALT, alanine transaminase; AST, aspartate transaminase; GGT, gamma-glutamyl transferase; Cr, creatinine; BUN, blood urea nitrogen; UA, uric acid; CCB, calcium channel blockers; ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; PAC, plasma aldosterone concentration; PA, primary aldosteronism.

Figure 3 Dose-response relationship between PAC and the new-onset NAFLD. (A) crude model, (B) adjusted model 1, (C) adjusted model 2, and (D) adjusted model 3. Adjusted for all non-collinear variables.

Figure 4 Association of the PAC (per 5 ng/dL increment) with new-onset NAFLD in various subgroups. Adjusted for all non-collinear variables, if not stratified.