Higher circulating Trimethylamine N-oxide levels are associated with worse severity and prognosis in pulmonary hypertension: a cohort study

Table 1 Baseline characteristics of patients with PH stratified by TMAO levels

Variables	Total PH patients N = 163	High TMAO group N = 91	Low TMAO group N = 72	P value
Age, years	36.3 (26.8, 52.8)	38.7 (29.0, 55.9)	33.6 (25.1, 50.1)	0.205
Female sex, n (%)	104 (63.8)	52 (57.1)	52 (72.2)	0.051
BMI, kg/m²	22.1 ± 3.9	23.0 ± 3.9	20.9 ± 3.7	0.001
6 MWD, m	409.0 (333.0, 480.0)	403.0 (267.0, 480.0)	412.0 (363.8.0, 483.8)	0.034
WHO-FC, n (%)
I–II	112 (68.7)	54 (59.3)	58 (80.6)	0.004
III–IV	51 (31.3)	37 (40.7)	14 (19.4)	0.004
Laboratories
TMAO, umol/L	2.0 (1.0, 3.9)	3.7 (2.4, 5.6)	0.8 (0.4, 1.3)	< 0.001
NT-proBNP, pg/ml	406.0 (139.9, 1061.0)	590.7 (204.8, 1748.5)	288.2 (98.6, 567.3)	< 0.001
Albumin, g	43.8 (40.8, 45.9)	43.2 (40.9, 46.0)	44.0 (40.7, 45.8)	0.971
Creatinine, umol/L	75.0 (65.2, 86.0)	78.0 (67.0, 91.0)	73.1 (63.5, 82.0)	0.054
Total cholesterol, mmol/L	4.1 (3.6, 5.1)	4.1 (3.5, 5.1)	4.2 (3.6, 4.9)	0.683
Echocardiography
LVEF, %	65.0 (60.0, 70.0)	65.0 (60.3, 70.0)	65.0 (60.0, 70.0)	0.967
RVD, mm	32.0 (26.0, 37.0)	33.5 (26.0, 38.0)	30.0 (26.0, 37.0)	0.009
TAPSE, mm	16.5 ± 4.1	15.6 ± 4.3	17.7 ± 3.4	0.001
Hemodynamics
mRAP, mmHg	6.2 ± 3.6	6.3 ± 3.7	6.0 ± 3.3	0.614
Cardiac index, L/min * m²	3.0 ± 1.1	2.8 ± 1.2	3.3 ± 0.9	0.005
PAWP, mmHg	9.0 (6.0, 11.0)	9.0 (6.3, 12.0)	8.0 (6.0, 10.0)	0.198
PVR, WU	8.9 ± 6.2	10.2 ± 5.5	7.4 ± 6.8	0.013
Risk stratification (COMPERA)				0.001
Low risk	73 (44.8)	32 (35.2)	41 (56.9)
Intermediate risk	79 (48.5)	49 (53.8)	30 (41.7)
High risk	11 (6.7)	10 (11.0)	1 (1.4)

Variables	Total PAH patients N = 112	High TMAO group N = 58	Low TMAO group N = 54	P value
Treatment, n (%)
ERAs	86 (76.8)	43 (74.1)	43 (79.6)	0.512
Prostacyclins	30 (26.8)	19 (32.8)	11 (20.4)	0.200
NO pathway	98 (87.5)	48 (82.8)	50 (92.6)	0.155
Monotherapy	20 (17.9)	12 (20.7)	8 (14.8)	0.467
Combination therapy	92 (82.1)	46 (79.3)	46 (85.2)	0.467

Variables	Total CTEPH patients N = 51	High TMAO group N = 33	Low TMAO group N = 18	P value
Riociguat	18 (35.3)	10 (30.3)	8 (44.4)	0.367
BPA/PEA	44 (86.3)	28 (84.8)	16 (88.9)	0.692

In this cohort, 112 PAH patients and 51 CTEPH patients were enrolled. Patients were divided into two groups according to the plasma TMAO levels (the cut-off value was 1.69 umol/L). The Kolmogorov–Smirnov was used for normality distribution test. Continuous variables were presented as mean ± standard deviation or median and interquartile ranges based on different data distributions
Categorical variables were presented as frequencies with percentages. Student’s t-test was used for continuous data with normal distribution, including BMI, TAPSE, mRAP, and CI, while the Wilcoxon rank-sum test was used for continuous data with non-normal distribution. Chi-square test was used for categorical variables
TMAO trimethylamine-N-oxide; BMI body mass index; 6 MWD 6-min walk distance; WHO-FC world health organization function class; NT-proBNP N-terminal pro-brain natriuretic peptide; LVEF left ventricular ejection fraction; RVD right ventricular diameter; TAPSE tricuspid annular plane systolic excursion; mRAP mean right atrial pressure; PAWP pulmonary arterial wedge pressure; PVR pulmonary vascular resistance; PAH pulmonary arterial hypertension; CTEPH chronic thromboembolic pulmonary hypertension; ERAs endothelin receptor agonists; NO nitric oxide; BPA balloon pulmonary angioplasty; PEA pulmonary endarterectomy

ISSN: 1465-993X