LDL cholesterol is associated with systemic vascular resistance and wave reflection in subjects naive to cardiovascular drugs

Figures & data

Figure 1. Supine aortic systolic (A) and diastolic (B) blood pressure, and aortic pulse pressure (C) and augmentation index (D) in age- and sex-adjusted quartiles (Q1-Q4) of LDL-cholesterol during 5-minute recordings. Q1 (n = 153), Q2 (n = 158), Q3 (n = 148) and Q4 (n = 156); mean ± standard error of the mean; *p < 0.05, ANOVA for repeated measurements.

Table 1. Age and sex adjusted characteristics of the study population in quartiles of LDL cholesterol.

	Overall	Q1	Q2	Q3	Q4
Number	615	153	158	148	156
Male / female	314 / 301	80 / 73	79 / 79	75 / 73	80 / 76
Age (years)	44.9 (11.9)	44.6 (11.8)	44.1 (12.6)	45.1 (12.6)	45.7 (10.7)
Age range (years)	19–72	20–67	19–71	20–72	21–72
BMI (kg/m^2)	26.8 (4.4)	25.6 (4.5)	26.4 (4.5)	27.2 (4.1)*	28.1 (4.2)*†
Alcohol (standard doses/week)	4.5 ( 5.7)	3.8 (4.9)	4.1 (5.1)	4.9 (6.5)	5.0 (6.3)
Smokers (number / percentage)	70/11.4%	14/9.1%	16/10.1%	21/14.2%	25/16.0%
Office blood pressure (mmHg)
Systolic	140.5 (21.1)	134.7 (19.9)	138.8 (20.9)	139.4 (19.8)*	149.0 (20.9)*†
Diastolic	89.3 (12.5)	85.3 (12.0)	88.6 (12.9)	90.0 (11.4)*	94.0(12.1)*†
eGFR (ml/min per 1.73 m^2)	98.8 (18.1)	102.0 (18.1)	101.3 (18.3)	97.7 (17.1)	94.2 (18.0)*†
QUICKI	0.358 (0.042)	0.369 (0.041)	0.365 (0.056)	0.349 (0.032)*†	0.349 (0.032)*†
Fasting plasma
Creatinine (μmol/l)	73.7 ( 13.5)	72.2 (12.3)	74.8 (14.1)	74.1 (13.5)	73.6 (13.9)
Cystatin C (mg/l)	0.85 (0.15)	0.82 (0.15)	0.83 (0.15)	0.85 (0.14)	0.89 (0.14)*†
Sodium (mmol/l)	140.3 (2.0)	140.3 (2.1)	140.4 (2.0)	140.5 (2.0)	140.3 (1.7)
Potassium (mmol/l)	3.81 (0.28)	3.82 (0.28)	3.81 (0.28)	3.84 (0.26)	3.77 (0.31)
Uric acid (μmol/l)	303 (76)	291 (78)	297 (79)	310 (76)	312 (71)
CRP (mg/l)	1.7 (2.9)	1.6 (3.0)	1.7 (4.1)	1.5 (1.5)	2.0 (2.2)
Total cholesterol (mmol/l)	5.15 (1.02)	4.23 (0.68)	4.78 (0.64)*	5.33 (0.63)*†	6.25 (0.85)*† #
Triglycerides (mmol/l)	1.23 (0.76)	1.05 (0.96)	1.17 (0.69)	1.23 (0.62)	1.49 (0.70)*† #
HDL-C (mmol/l)	1.58 (0.44)	1.71 (0.488)	1.54 (0.41)*	1.56 (0.41)*	1.52 (0.43)*
LDL-C cholesterol (mmol/l)	3.05 (0.95)	2.05 (0.51)	2.75 (0.48)*	3.26 (0.50)*†	4.15 (0.75)*†#
Insulin (mU/L)	8.9 (17.0)	7.2 (5.6)	7.9 (6.1)	11.6 (33.3)	9.1 (5.4)
Glucose (mmol/l)	5.44 (0.58)	5.34 (0.69)	5.40 (0.59)	5.49 (0.48)	5.55 (0.54)*

Mean (standard deviation), *p < 0.05 vs Q1; †p < 0.05 vsQ2; #p < 0.05 vs Q3; BMI, body mass index; eGFR, cystatin C based CDK-EPI formula for estimated glomerular filtration rate [31]; QUICKI, quantitative insulin sensitivity check index [30]. CRP: C-reactive protein; HDL-C: high density lipoprotein cholesterol; LDL-C: low density lipoprotein cholesterol.

Figure 2. Heart rate (A), cardiac index (B), systemic vascular resistance index (C), and pulse wave velocity (D) in age- and sex-adjusted quartiles of LDL-cholesterol during 5-minute recordings. Quartiles as in Figure 1; mean ± standard error of the mean; *p < 0.05, ANOVA for repeated measurements.

Table 2.  Explanatory factors for haemodynamic variables in linear regression analyses with stepwise elimination.

	B	Beta	R squared	p		B	Beta	R squared	p
Aortic systolic blood pressure: model 1					Aortic systolic blood pressure: model 2
(Constant)	−16.615			0.738	(Constant)	−98.362			0.044
eGFR	−0.222	−0.208	0.205	<0.001	PWV	77.269	0.377	0.306	<0.001
LDL-C	3.343	0.165	0.259	<0.001	eGFR	−0.187	−0.175	0.352	<0.001
Age	0.332	0.204	0.285	<0.001	LDL-C	2.586	0.128	0.366	0.001
BMI	0.531	0.122	0.304	0.003	Sodium	1.077	0.109	0.374	0.001
Sodium	0.945	0.096	0.312	0.006	QUICKI	−34.232	−0.076	0.380	0.036
QUICKI	−38.761	−0.086	0.317	0.026	HDL-C	4.509	0.103	0.384	0.005
					BMI	0.434	0.099	0.389	0.014
Aortic diastolic blood pressure: model 1					Aortic diastolic blood pressure: model 2
(Constant)	19.283			0.588	(Constant)	−32.811			0.316
eGFR	−0.204	−0.286	0.170	<0.001	PWV	54.974	0.401	0.244	<0.001
LDL-C	2.265	0.168	0.217	<0.001	eGFR	−0.155	−0.218	0.284	<0.001
QUICKI	−33.714	−0.112	0.238	0.005	QUICKI	−35.114	−0.116	0.306	0.001
Sex	2.564	0.099	0.252	0.008	Alcohol amount	0.198	0.088	0.317	0.011
BMI	0.283	0.097	0.257	0.021	Sodium	0.628	0.095	0.324	0.005
Sodium	0.525	0.080	0.261	0.032	Age	−0.149	−0.137	0.330	0.006
					LDL-C	1.466	0.109	0.337	0.006
Aortic pulse pressure: model 1					Aortic pulse pressure: model 2
(Constant)	−46.757			0.092	(Constant)	−50.479			0.076
Age	0.307	0.354	0.206	<0.001	Age	0.190	0.219	0.206	<0.001
BMI	0.355	0.152	0.223	<0.001	PWV	24.365	0.222	0.238	<0.001
LDL-C	1.331	0.123	0.230	0.003	eGFR	−0.047	−0.083	0.244	0.064
HDL-C	2.398	0.102	0.235	0.012	BMI	0.291	0.125	0.248	0.003
Sodium	0.417	0.079	0.240	0.032	HDL-C	2.677	0.114	0.255	0.005
					Sodium	0.393	0.074	0.259	0.041
Augmentation index: model 1					Augmentation index: model 2
(Constant)	−1.268			0.414	(Constant)	7.678			0.016
Age	0.576	0.570	0.350	<0.001	Age	0.532	0.527	0.350	<0.001
Sex	−9.060	−0.378	0.483	<0.001	Sex	−9.687	−0.404	0.483	<0.001
LDL-C	0.841	0.067	0.485	0.043	SVRI	0.005	0.247	0.549	<0.001
					Heart rate	−0.205	−0.164	0.576	<0.001
					Smoker	2.930	0.080	0.583	0.003
					BMI	−0.240	−0.088	0.587	0.004
					LDL-C	0.774	0.062	0.589	0.047
Pulse wave velocity: model 1					Pulse wave velocity: model 2
(Constant)	0.566			<0.001	(Constant)	0.916			<0.001
Age	0.004	0.544	0.419	<0.001	Age	0.004	0.501	0.419	<0.001
Uric acid	0.0002	0.172	0.493	<0.001	Aortic systolic blood pressure	0.001	0.281	0.510	<0.001
Triglycerides	0.013	0.102	0.509	0.002	Uric acid	0.0002	0.154	0.555	<0.001
LDL-C	0.011	0.116	0.518	0.001	Triglycerides	0.012	0.095	0.568	0.003
Smoker	−0.023	−0.081	0.525	0.005	Smoker	−0.019	−0.067	0.571	0.013
BMI	0.002	0.080	0.528	0.019	HDL-C	−0.019	−0.088	0.575	0.006
					Sodium	−0.003	−0.056	0.578	0.045
Systemic vascular resistance index: model 1
(Constant)	3417.956			<0.001
eGFR	−5.613	−0.172	0.106	<0.001
Weight	9.149	0.246	0.142	<0.001
Age	5.122	0.103	0.159	0.031
Smoker	−220.835	−0.123	0.171	0.001
Height	−8.445	−0.133	0.181	0.005
LDL-C	64.294	0.104	0.188	0.016

For all these analyses, the skewed distribution of pulse wave velocity (PWV) was Lg10 transformed.

Variables in model 1: age, sex, body mass index (BMI) (for systemic vascular resistance BMI was replaced by height and weight), smoking status, consumption of standard drinks of alcohol per week, quantitative insulin sensitivity check index (QUICKI) [30], plasma C-reactive protein (CRP), sodium, uric acid, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglycerides, and cystatin C based CDK-EPI formula for estimated glomerular filtration rate (eGFR) [31].

Variables in model 2: model 1 + PWV; for augmentation index: model 1 + heart rate, systemic vascular resistance index (SVRI), and PWV; for PWV: model 1 + aortic systolic blood pressure.

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