Metabolically Healthy, but Obese Individuals and Associations with Echocardiographic Parameters and Inflammatory Biomarkers: Results from the CARLA Study

Figures & data

Table 1 Demographic and Clinical Characteristics of Study Participants

Characteristics	MHNW (n=345)	MHO (n=60)	MUNW (n=638)	MUO (n=369)	p value
Continuous variables Mean ± SD/median (IQR)
Age, years	64.0±9.6	64.2±8.4	68.9±9.7*	67.7±9.0*	<0.0001
BMI, kg/m^2	25.0±2.7	34.1±3.4*	26.4±2.4*	33.8±3.8*	<0.0001
Waist circumference, cm	89.1±10.9	109.3±10.5*	96.4±9.6*	112.9±10.4*	<0.0001
Systolic BP, mmHg	130.9±17.9	133.7±17.4	139.3±19.9*	139.9±19.6*	<0.0001
Diastolic BP, mmHg	79.5±9.1	80.9±9.0	80.1±10.8	79.9±10.3	0.68
Heart rate, beats/min	69.2±10.2	70.5±10.5	68.4±11.0	68.9±11.5	0.41
Cholesterol, mmol/L	5.6±0.9	5.6±1.0	5.4±1.1*	5.3±1.0*	0.0002
HDL, mmol/L	1.6±0.4	1.5±0.3	1.3±0.4*	1.2±0.3*	<0.0001
Triglycerides, mmol/L	1.2 (0.9–1.5)	1.3 (1.1–1.5)	1.9 (1.4–2.6)*	1.9 (1.4–2.7)*	<0.0001
Apo A1, g/L	1.7±0.3	1.6±0.2	1.5±0.3*	1.4±0.2*	<0.0001
Apo B, g/L	0.89±0.2	0.88±0.2	0.93±0.2	0.95±0.2*	0.007
Glucose, mmol/L	5.1 (4.8–5.4)	5.2 (5.0–5.4)	5.6 (5.1–6.1)*	5.8 (5.2–6.8)*	<0.0001
HbA1c, %	5.5±0.4	5.7±0.4	5.9±0.8*	6.2±0.9*	<0.0001
hsCRP, mg/L	1.1 (0.7–2.1)	3.2 (1.7–5.1)*	1.5 (0.9–3.0)*	2.8 (1.6–5.4)*	<0.0001
IL-6, pg/mL	1.8 (1.0–2.9)	3.1 (2.4–4.7)*	2.3 (1.0–3.8)*	3.2 (2.3–5.1)*	<0.0001
sTNF-R1, pg/mL	1078.1 (946.9–1266.1)	1281.8* (1140.1–1452.3)	1201.5* (1052.6–1437.2)	1286.9* (1135.3–1574.7)	<0.0001
NT-proBNP, pg/mL	86.5 (52.2–161.2)	85.3 (41.6–157.1)	125.9* (62.1–244.3)	119.2* (59.1–236.6)	<0.0001
γ-GT, ukat/L	0.4 (0.3–0.5)	0.4 (0.3–0.6)	0.4 (0.3–0.7)*	0.5 (0.4–0.8)*	<0.0001
eGFR, mL/min/1.73 m^2	85.1±15.7	81.8±16.6	78.6±18.3*	78.1±18.3*	<0.0001
Categorical variables n (%)
Women	186 (53.9)	43 (71.6)	235 (36.8)	167 (45.3)	<0.0001
Current sport activity	186 (53.9)	34 (56.7)	293 (45.9)	147 (39.8)	0.0008
Current smokers	68 (19.7)	7 (11.7)	101 (15.8)	45 (12.2)	0.03
University education	111 (32.2)	10 (16.7)	181 (28.4)	90 (24.4)	0.02
Diabetes medication	3 (0.9)	1 (1.7)	97 (15.2)	96 (26.0)	<0.0001
Antihypertensive medication	108 (31.3)	29 (48.3)	463 (72.6)	307 (83.2)	<0.0001
Lipid-lowering medication	7 (2.0)	2 (3.3)	217 (34.0)	116 (31.4)	<0.0001

Notes: Results presented as mean ± SD for normally distributed residuals with one-way ANOVA p-values reported, when there was equal variance between groups, or Welch ANOVA. p-values reported, when variance was unequal. Frequencies with percentages for categorical variables (Chi-square or Fisher’s exact test). Non-normally distributed residuals reported with median and IQR (p-value from Kruskal–Wallis test). Games-Howell or Tukey-Kramer post-hoc test (after ANOVA) and Dunn’s post-hoc test (after Kruskal–Wallis). * significant difference (p<0.05) when compared to the reference group (MHNW).

Abbreviations: MHNW, metabolically healthy, normal weight; MHO, metabolically healthy obese; MUNW, metabolically unhealthy, normal weight; MUO, metabolically unhealthy obese; IQR, interquartile range; SD, standard deviation.

Table 2 Echocardiographic Characteristics of Study Participants

Characteristics	MHNW (n=345)	MHO (n=60)	MUNW (n=638)	MUO (n=369)	p value
LA structure
LA diameter, mm	37.41±5.4	39.98±5.3*	40.40±5.3*	43.20±5.4*	<0.0001
LA volume, mL	35.25±18.3	43.06±18.5*	39.85±18.9*	48.32±18.9*	<0.0001
LV structure
Mass/height^1.7, g/m^1.7	74.89±26.5	85.89±27.4*	87.15±27.8*	98.79±26.5*	<0.0001
Septal thickness, mm	10.75±2.2	11.30±2.4	11.58±2.4*	11.84±2.4*	<0.0001
Posterior wall thickness, mm	10.34±2.3	10.69±2.3	10.91±2.2*	11.29±2.4*	<0.0001
Diastolic volume, mL	89.2±37.5	98.1±38.4	95.1±37.8	106.2±38.5*	<0.0001
Systolic volume, mL	34.0±17.4	36.0±17.8	36.7±17.6	40.9±18.0*	<0.0001
Diastolic diameter, mm	46.85±6.7	48.52±7.3	48.89±7.3*	51.38±7.0*	<0.0001
Systolic diameter, mm	29.32±6.5	30.02±7.2	30.65±6.6*	32.40±6.7*	<0.0001
LV systolic function
Ejection fraction, %	60.61±7.0	61.62±7.2	60.24±7.0	60.34±7.3	0.49
LV diastolic function
E/A ratio	1.06±0.4	1.03±0.4	1.02±0.4	0.99±0.4	0.19
E/e´ ratio	10.40±4.5	11.08±4.5	11.85±4.4*	12.59±4.6*	<0.0001
E peak, cm/s	66.2±18.0	68.42±17.8	66.0±17.9	70.37±18.4*	0.001
A peak, cm/s	66.0±20.9	68.57±20.5	70.0±20.8*	75.6±21.2*	<0.0001
e’ peak, cm/s	6.78±1.8	6.52±1.9	5.97±1.8*	5.91±1.8*	<0.0001
a’ peak, cm/s	9.58±2.3	9.62±2.3	9.46± 2.3	9.26±2.3	0.27

Notes: Results presented as mean ± SD for normally distributed residuals, difference in means ANOVA for equal variance or Welch ANOVA for unequal variance with Tukey-Kramer post-hoc test. * significant difference (p<0.05) when compared to the reference group (MHNW).

Abbreviations: MHNW, metabolically healthy, normal weight; MHO, metabolically healthy obese; MUNW, metabolically unhealthy, normal weight; MUO, metabolically unhealthy obese; LA, left atrium; LV, left ventricle; SD, standard deviation.

Figure 1 Differences in means with 95% CI for selected echocardiographic parameters.

Abbreviations: MHNW, metabolically healthy, normal weight; MHO, metabolically healthy obese; MUNW, metabolically unhealthy, normal weight; MUO, metabolically unhealthy obese; LV, left ventricle; CI, confidence interval.

Table 3 Multivariable-Adjusted Regression Models for Echocardiographic Parameters

Echocardiographic Parameters	MHNW (n=345)	MHO (n=60)	p-value	MUNW (n=638)	p-value	MUO (n=369)	p-value
LA diameter, mm
Model 1	Reference	3.06 (1.67 to 4.46)	<0.0001	2.08 (1.39 to 2.77)	<0.0001	5.24 (4.48 to 6.00)	<0.0001
Model 2	Reference	2.73 (1.35 to 4.11)	<0.0001	1.39 (0.65 to 2.13)	0.0002	4.31 (3.48 to 5.15)	<0.0001
LA volume, mL
Model 1	Reference	8.78 (3.77 to 13.79)	0.0006	2.59 (0.13 to 5.04)	0.03	11.80 (9.08 to 14.52)	<0.0001
Model 2	Reference	7.86 (2.88 to 12.83)	0.002	0.19 (−2.44 to 2.83)	0.88	8.81 (5.84 to 11.79)	<0.0001
LVMI, g/m^1.7
Model 1	Reference	12.84 (5.45 to 20.23)	0.0007	8.71 (5.11 to 12.30)	<0.0001	21.70 (17.81 to 25.59)	<0.0001
Model 2	Reference	11.82 (4.43 to 19.22)	0.001	5.90 (2.04 to 9.76)	0.002	18.21 (13.88 to 22.54)	<0.0001
IVSd, mm
Model 1	Reference	0.68 (0.03 to 1.33)	0.03	0.62 (0.33 to 0.92)	<0.0001	0.97 (0.64 to 1.29)	<0.0001
Model 2	Reference	0.64 (−0.007 to 1.28)	0.05	0.59 (0.27 to 0.91)	0.0003	0.89 (0.54 to 1.25)	<0.0001
LVPWd, mm
Model 1	Reference	0.50 (−0.12 to 1.13)	0.11	0.34 (0.04 to 0.65)	0.02	0.82 (0.47 to 1.16)	<0.0001
Model 2	Reference	0.47 (−0.15 to 1.10)	0.13	0.33 (0.002 to 0.66)	0.04	0.80 (0.43 to 1.18)	<0.0001
LVVd, mL
Model 1	Reference	13.02 (2.94 to 23.10)	0.01	4.63 (−0.18 to 9.45)	0.05	16.94 (11.64 to 22.23)	<0.0001
Model 2	Reference	12.42 (2.30 to 22.55)	0.01	3.03 (−2.21 to 8.28)	0.25	15.01 (9.11 to 20.91)	<0.0001
LVVs, mL
Model 1	Reference	3.68 (−1.06 to 8.42)	0.12	1.91 (−0.36 to 4.19)	0.09	6.69 (4.17 to 9.22)	<0.0001
Model 2	Reference	3.52 (−1.24 to 8.28)	0.14	1.05 (−1.43 to 3.54)	0.40	5.75 (2.94 to 8.56)	<0.0001
LVDd, mm
Model 1	Reference	2.44 (0.55–4.32)	0.01	1.39 (0.48 to 2.30)	0.002	4.21 (3.21 to 5.22)	<0.0001
Model 2	Reference	2.20 (0.33 to 4.07)	0.02	0.66 (−0.30 to 1.63)	0.17	3.34 (2.23 to 4.45)	<0.0001
LVDs, mm
Model 1	Reference	1.31 (−0.58 to 3.20)	0.17	0.76 (−0.09 to 1.61)	0.08	2.80 (1.83 to 3.76)	<0.0001
Model 2	Reference	1.19 (−0.68 to 3.08)	0.21	0.07 (−0.84 to 0.98)	0.87	2.02 (0.97 to 3.07)	0.0002
EF, %
Model 1	Reference	0.90 (−1.07 to 2.88)	0.37	−0.07 (−1.01 to 0.85)	0.86	−0.08 (−1.14 to 0.98)	0.88
Model 2	Reference	0.82 (−1.16 to 2.81)	0.41	0.04 (−0.97 to 1.06)	0.93	−0.0001 (−1.18 to 1.18)	0.99
E/A ratio
Model 1	Reference	−0.01 (−0.12 to 0.09)	0.77	−0.006 (−0.05 to 0.04)	0.80	−0.03 (−0.09 to 0.01)	0.19
Model 2	Reference	−0.02 (−0.13 to 0.08)	0.63	−0.02 (−0.08 to 0.02)	0.32	−0.06 (−0.12 to −0.001)	0.05
E/e´ ratio
Model 1	Reference	0.56 (−0.63 to 1.75)	0.35	0.93 (0.35 to 1.51)	0.001	1.78 (1.14 to 2.42)	<0.0001
Model 2	Reference	0.39 (−0.79 to 1.58)	0.51	0.43 (−0.19 to 1.05)	0.17	1.03 (0.33 to 1.74)	0.003
E peak, cm/s
Model 1	Reference	1.65 (−3.22 to 6.52)	0.50	0.39 (−2.01 to 2.80)	0.74	4.46 (1.77 to 7.14)	0.001
Model 2	Reference	1.15 (−3.71 to 6.02)	0.64	−1.33 (−3.94 to 1.26)	0.31	1.97 (−0.98 to 4.93)	0.19
A peak, cm/s
Model 1	Reference	1.32 (−4.01 to 6.66)	0.62	1.87 (−0.79 to 4.54)	0.16	7.71 (4.76 to 10.65)	<0.0001
Model 2	Reference	1.42 (−3.91 to 6.76)	0.60	1.62 (−1.26 to 4.51)	0.26	6.85 (3.60 to 10.10)	<0.0001
e’ peak, cm/s
Model 1	Reference	−0.25 (−0.73 to 0.22)	0.29	−0.48 (−0.71 to −0.25)	<0.0001	−0.63 (−0.89 to −0.37)	<0.0001
Model 2	Reference	−0.20 (−0.68 to 0.27)	0.39	−0.39 (−0.64 to −0.14)	0.001	−0.50 (−0.79 to −0.21)	0.0006
a’ peak, cm/s
Model 1	Reference	0.11 (−0.50 to 0.73)	0.71	−0.03 (−0.35 to 0.27)	0.80	−0.24 (−0.58 to 0.09)	0.16
Model 2	Reference	0.19 (−0.41 to 0.81)	0.52	0.21 (−0.12 to 0.55)	0.21	0.06 (−0.30 to 0.44)	0.72

Notes: Results presented as effect estimate±95% CI, effect estimate considered significant if α≤0.003. Model 1 is adjusted for age and sex. Model 2 is adjusted for Model 1 and sport activity, current smoking and use of medication for hypertension, diabetes or hyperlipidemia.

Abbreviations: LA, left atrium; LV, left ventricle; LVMI, LV mass index; IVSd, interventricular septal diameter; LVPWd, LV posterior wall diameter; LVVd/LVVs, LV end-diastolic/end-systolic volume; LVDd/LVDs, LV end-diastolic/end-systolic diameter; EF, ejection fraction; CI, confidence interval.

Figure 2 Forest plots of odds ratios and 95% CI for inflammatory biomarkers. Model 1 – age and sex adjusted. Odds ratios shown are for a 1-SD increment.

Abbreviations: MHNW, metabolically healthy, normal weight; MHO, metabolically healthy obese; MUNW, metabolically unhealthy, normal weight; MUO, metabolically unhealthy obese; CI, confidence interval.