On-treatment HDL cholesterol predicts incident atrial fibrillation in hypertensive patients with left ventricular hypertrophy

Figures & data

Table 1. Study baseline demographic and clinical characteristics in relation to quartiles of HDL cholesterol levels at baseline.

Variables	HDL: ≤1.21 (n = 2271)	HDL: 1.22–1.47 (n = 2105)	HDL: 1.48–1.78 (n = 1977)	HDL: >1.78 (n = 1914)	p Value
Age (years)	66.4 ± 7.0	66.6 ± 6.9	66.9 ± 7.0	67.3 ± 7.1	<0.001
Sex (% female)	33.0	49.8	61.9	77.1	<0.001
Race (% Black)	5.9	5.5	6.8	5.5	0.292
Diabetes (%)	20.5	13.5	8.8	6.0	<0.001
History of ischaemic heart disease (%)	20.4	16.5	12.7	10.6	<0.001
History of myocardial infarction (%)	8.6	6.8	4.4	3.2	<0.001
History of stroke (%)	4.7	4.4	3.7	3.6	0.228
History of heart failure (%)	2.2	1.3	1.2	1.0	0.003
History of peripheral vascular disease (%)	6.5	4.8	5.0	5.3	0.049
Current smoker (%)	18.4	15.7	15.0	16.4	0.016
Prior antihypertensive treatment (%)	75.6	71.4	72.6	67.1	<0.001
Randomised Treatment (% Losartan)	49.5	51.4	50.1	50.5	0.660
Body mass index (kg/m^2)	29.2 ± 4.6	28.4 ± 4.6	27.8 ± 4.9	26.4 ± 4.7	<0.001
Serum glucose (mM)	6.59 ± 2.67	6.06 ± 2.23	5.72 ± 1.69	5.52 ± 1.67	<0.001
Total cholesterol (mM)	5.75 ± 1.15	6.00 ± 1.10	6.11 ± 1.06	6.40 ± 1.05	<0.001
HDL cholesterol (mM)	1.02 ± 0.14	1.34 ± 0.07	1.62 ± 0.09	2.12 ± 0.31	n.a.
Creatinine (mg/mM)	93.7 ± 21.4	86.9 ± 18.5	83.8 ± 18.1	80.2 ± 19.0	<0.001
UACR (mg/mM)	8.9 ± 27.5	6.9 ± 34.3	6.5 ± 32.2	5.5 ± 22.4	0.003

HDL: high density lipoprotein; UACR: urine albumin/creatinine ratio; n.a.: not applicable

Table 2. Study baseline and change from study baseline to last in-study measurement of blood pressure, electrocardiographic left ventricular hypertrophy and heart rate in relation to quartiles of HDL cholesterol levels at baseline.

Variables	HDL: ≤1.21 (n = 2271)	HDL: 1.22–1.47 (n = 2105)	HDL: 1.48–1.78 (n = 1977)	HDL: >1.78 (n = 1914)	p –Value
Baseline measurements
Systolic BP (mm Hg)	173.5 ± 14.6	174.0 ± 14.2	175.0 ± 14.3	174.9 ± 13.9	0.001
Diastolic BP (mm Hg)	97.5 ± 9.1	97.8 ± 8.7	97.9 ± 8.7	98.0 ± 8.6	0.301
Cornell product (mm × ms)	2837 ± 997	2841 ± 1013	2794 ± 985	2800 ± 1087	0.317
Sokolow-Lyon voltage (mm)	29.4 ± 10.4	29.3 ± 10.3	30.2 ± 10.3	31.0 ± 10.4	<0.001
Heart rate (bpm)	73.6 ± 11.0	73.4 ± 11.0	73.5 ± 11.0	74.3 ± 10.8	0.043
Change from baseline to last measurement
Systolic BP (mm Hg)	−29.4 ± 19.5	−29.1 ± 18.9	−29.9 ± 19.4	−29.5 ± 20.0	0.578
Diastolic BP (mm Hg)	−17.5 ± 10.4	−17.0 ± 10.2	−16.8 ± 10.1	−17.1 ± 10.2	0.135
Cornell product (mm × ms)	−176 ± 883	−211 ± 814	−207 ± 830	−210 ± 860	0.460
Sokolow-Lyon voltage (mm)	−3.6 ± 7.3	−3.8 ± 7.0	−3.8 ± 7.2	−4.2 ± 7.2	0.036
Heart rate (bpm)	−5.5 ± 12.7	−5.0 ± 12.6	−4.7 ± 12.9	−4.7 ± 12.6	0.095

HDL: high density lipoprotein; BP: blood pressure.

Table 3. Univariate and multivariable cox regression analyses to assess the relation of new onset atrial fibrillation to quartiles of baseline and on-treatment high density lipoprotein (HDL) cholesterol levels.

Analysis	Hazard ratios (95% confidence interval)
	Quartile 1	Quartile 2	Quartile 3	Quartile 4
	HDL: ≤⩽1.21	HDL: 1.22–1.47	HDL: 1.48–1.78	HDL: >1.78
Univariate Cox model
Baseline HDL	1.14 (0.90–1.43)	1.24 (0.99–1.56)	1.30 (1.04–1.63)	1
On-treatment HDL	1.53 (1.19-1.97)	1.35 (1.04-1.75)	1.27 (0.97-1.65)	1
Multivariable Cox model^a
Baseline HDL	1.01 (0.78–1.31)	1.24 (0.97–1.58)	1.24 (0.97–1.57)	1
On-treatment HDL^b	1.54 (1.16–2.05)	1.41 (1.07–1.85)	1.34 (1.02–1.76)	1

^a Randomised treatment, age, sex, race, prior antihypertensive treatment, history of MI, ischaemic heart disease, heart failure, diabetes, baseline serum glucose and creatinine, urine albumin/creatinine ratio treated as standard covariates, incident myocardial infarction, incident heart failure, on-treatment non-HDL cholesterol, heart rate, Cornell product left ventricular hypertrophy, diastolic and systolic pressure, and statin use treated as time-varying covariates.

^b Also adjusted for baseline HDL cholesterol level.

Figure 1. Survival curves illustrating the rate of new-onset atrial fibrillation in relation to quartiles of on-treatment HDL cholesterol levels.

Table 4. Multivariable Cox analyses to assess the predictive value of on-treatment high density lipoprotein (HDL) for new-onset atrial fibrillation in relevant subgroups of the study population.

Subgroup	New atrial fibrillation (n)	Hazard ratio^a	95% Confidence interval	p value for interaction
Sex				0.824
Female (n = 4498)	315	3.00	2.64–3.41
Male (n = 3769)	330	3.22	2.77–3.76
Age				0.338
<65 years (n = 3209)	138	3.24	2.59–4.05
≥65 years (n = 5058)	507	3.10	2.78–3.46
Prior antihypertensive treatment				0.132
No (n = 2326)	152	3.49	2.88–4.22
Yes (n = 5941)	493	2.94	2.63–3.29
Race				0.899
White/other (n = 7776)	624	3.06	2.77–3.38
Black (n = 491)	21	2.67	1.47–4.25
Randomised treatment				0.220
Atenolol (n = 4105)	341	3.01	2.61–3.46
Losartan (n = 4162)	304	3.14	2.74–3.59
Statin treatment				0.992
No statin during the study (n = 6239)	498	2.98	2.67–3.32
Statin treatment (n = 2028)	147	3.54	2.81–4.46

^a Hazard ratio for 1 SD of mean of baseline HDL (0.44 mmol/l) lower HDL entered as a continuous variable adjusted for same covariates as in Table 3.

Data availability statement

The data that support the findings of this study are available from the corresponding author, P.M.O. upon reasonable request.