Prevalence, Treatment Pattern and Resource Use in Patients with Mixed Dyslipidemia Using Lipid Modifying Agents in Korea (PRIMULA): An Observational Study

Chan Seok Park; Hyo-Soo Kim; Sang-Hak Lee; Ki Hoon Han; Sang-Hyun Kim; Doo-Il Kim; Moon-Kyu Lee; Ji Dong Sung; Young-Keun Ahn; Jae-Hyeong Park; Sang-Hong Baek

doi:10.12997/jla.2016.5.2.121

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Park, Kim, Lee, Han, Kim, Kim, Lee, Sung, Ahn, Park, and Baek: Prevalence, Treatment Pattern and Resource Use in Patients with Mixed Dyslipidemia Using Lipid Modifying Agents in Korea (PRIMULA): An Observational Study

Original Article

J Lipid Atheroscler 2016;5(2):121-131.

Published online: 31 December 2016

DOI: https://doi.org/10.12997/jla.2016.5.2.121

Prevalence, Treatment Pattern and Resource Use in Patients with Mixed Dyslipidemia Using Lipid Modifying Agents in Korea (PRIMULA): An Observational Study

Chan Seok Park¹, Hyo-Soo Kim², Sang-Hak Lee³, Ki Hoon Han⁴, Sang-Hyun Kim⁵, Doo-Il Kim⁶, Moon-Kyu Lee⁷, Ji Dong Sung⁸, Young-Keun Ahn⁹, Jae-Hyeong Park¹⁰, Sang-Hong Baek¹

¹Division of Cardiology, Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea

²Division of Cardiology, Department of Internal Medicine, Seoul National University, Seoul National University Hospital, Seoul, Korea

³ Cardiology Division, Department of Internal Medicine, Yonsei University College of Medicine, Severance Cardiovascular Hospital, Seoul, Korea

⁴Department of Cardiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea

⁵Division of Cardiology, Department of Internal Medicine, Seoul Boramae Hospital, Seoul, Korea

⁶Division of Cardiology, Department of Internal Medicine, Inje University Haeundae Paik Hospital, Busan, Korea

⁷Division of Endocrinology and Metabolism, Department of Internal Medicine, Samsung Medical Center, Seongkyunkwan University School of Medicine, Seoul, Korea

⁸ Division of Cardiology, Department of Internal Medicine, Samsung Medical Center, Seongkyunkwan University School of Medicine, Seoul, Korea

⁹Division of Cardiology, Department of Internal Medicine, Chonnam National University Hospital, Chonnnam National University, Gwangju, Korea

¹⁰Cardiology Division of Internal Medicine, Chungnam National University, Chungnam National University Hospital, Daejeon, Korea

Corresponding Author: Sang-Hong Baek, Division of Cardiovascular Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, 222 Banpodae-ro, Seocho-gu, Seoul 06591, Korea Tel: +82-2-2258-6030, Fax: +82-2-951-1506, E-mail: whitesh@catholic.ac.kr

Received 27 April 2016 Revised 9 June 2016 Accepted 15 June 2016

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Objective

Limited information is available on the effectiveness of lipid-modifying therapy (LMT) for low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) in the Korean population. The objective of this study was to describe the prevalence of different types of lipid disorders in Korean patients using LMT.

Methods

Eight hundred seventy-one dyslipidemia patients, who were LMT-naive for >1 year prior to retrospective enrollment, were included for analysis. Serum levels of LDL-C, HDL-C, TG and total cholesterol (TC) were assessed after >1 year of LMT. We also analyzed the therapeutic effects of LMT in the subjects with high cardiovascular risk factors (n=629), atherosclerotic cardiovascular disease (ASCVD) (n=296) or diabetes without ASCVD (n=316).

Results

The rates of elevated LDL-C without other abnormal lipids levels, elevated TG or decreased HDL-C (with normal LDL-C levels) and high LDL-C combined with elevated TG and/or decreased HDL-C were 33.4%, 13.0% and 53.6%, respectively. After at least one year on LMT (statin alone: 81%, statin and cholesterol absorption inhibitor: 10%, fibrates alone: 3%, others: 3%), 61% of patients had at least one lipid abnormality, with 3.4% failing to reach the therapeutic LDL-C target level or a normal level of HDL-C and TG. After LMT, 64.9% of patients with high cardiovascular risk factors, 64.5% of those with ASCVD or and 64.2% of those with diabetes without ASCVD also had at least one lipid abnormality.

Conclusion

Approximately two-thirds of patients did not reach the target or normal lipid profile after taking LMT, irrespective of combining disease and high cardiovascular risk factors. Tight lipid control is required, especially in patients with dyslipidemia and high cardiovascular risk factors or comorbid diseases.

Keywords: Dyslipidemias, LDL Cholesterol, HDL Cholesterol, Triglyderide, Primary care

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Fig. 1.

Distribution of dyslipidemia according to the underlying diseases and risk factors. Abbreviations: Atherosclerotic cardiovascular disease (ASCVD), Diabetes mellitus (DM), FRS (Framingham risk score), Low-density lipoprotein cholesterol (LDL-C), Triglyceride (TG), High-density lipoprotein cholesterol (HDL-C).

Table 1.

Characteristics of patients before initiating pharmacotherapy for dyslipidemia

Variable	Total sample	No high-risk conditions	High-risk conditions
Variable			ASCVD	DM without ASCVD	FRS>20% without ASCVD & DM
n (%)	871 (100.0)	242 (27.8)	296 (34.0)	316 (36.2)	17 (2.0)
Age (year)	58.7±10.1	58.1±10.0	60.8±10.0	57.0±9.8	62.4±12.2
Men (n (%))	449 (51.6)	102 (42.2)	189 (63.9)^**	144 (45.6)	14 (82.4)
Current smokers	147 (16.9)	26 (10.7)	79 (26.7)^**	36 (11.4)	6 (35.3)^**
Body mass index (kg/m²)	25.2±3.0	25.1±2.9	25.3±3.0	25.1±3.2	25.8±2.7
Systolic blood pressure (mmHg)	123.0±17.4	130.2±17.1	126.8±17.6	132.9±17.3	135.8±8.1
Diastolic blood pressure (mmHg)	79.3±11.2	80.6±10.9	77.3±11.5	80.3±10.9	82.4±8.4
Hypertension (n (%))	697 (80.0)	174 (71.9)	271 (91.6)^**	236 (74.7)	16 (94.1)
Total cholesterol (mg/dL)	223.0±38.7	239.9±36.1	205.8±38.8^**	225.6±34.1^**	233.9±34.0
LDL-C (mg/dL)	146.7±36.5	161.9±33.5	138.1±35.1^**	142.4±36.6^**	157.1±35.9
TG (mg/dL)	193.9±119.4	189.9±120.8	166.5±99.1	221.0±124.9	225.2±192.8
HDL-C (mg/dL)	48.3±12.5	52.8±12.6	44.7±12.3^**	48.5±11.6^**	41.8±6.8^**
Non-HDL-C (mg/dL)	174.7±35.3	187.1±4.3	161.0±34.9^**	177.1±32.1^*	192.2±32.5
Fasting plasma glucose (mg/dL)	127.6±49.2	100.5±13.8	122.6±47.8^**	151.9±55.1^**	98.3±16.4

Data are expressed as number (percentage) or as mean±SD.

^** Significantly different from those with no high-risk conditions (p<0.0001)

^* Significantly different from those with no high-risk conditions (p<0.001)

ASCVD; Atherosclerotic cardiovascular disease, DM; Diabetes mellitus, FRS; Framingham risk score, LDL-C; Low-density lipoprotein cholesterol, TG; Triglyceride, HDL-C; High-density lipoprotein cholesterol

Table 2.

Distribution of lipid abnormalities

Variable		Total sample	No high-risk conditions	High-risk conditions
Variable				ASCVD	DM without ASCVD	FRS>20% without ASCVD & DM
		(n=871)	(n=242)	(n=296)	(n=316)	(n=17)
Baseline
	High LDL-C only, n (%)	291 (33.4)	95 (39.2)	114 (38.5)	78 (24.7)	4 (23.5)
	Elevated TG or decreased HDL-C (with normal LDL-C levels), n (%)	113 (13.0)	37 (15.3)	40 (13.5)	33 (10.4)	3 (17.6)
	High LDL-C combined with elevated TG and/or decreased HDL-C, n (%)	467 (53.6)	110 (45.5)	142 (48.0)	205 (64.9)	10 (58.8)
Follow-up
	No abnormalities, n (%)	340 (39.0)	119 (49.2)	105 (35.5)	113 (35.8)	3 (17.7)
	High LDL-C only, n (%)	79 (9.1)	15 (6.2)	28 (9.4)	33 (10.4)	3 (17.7)
	Elevated TG or decreased HDL-C (with normal LDL-C levels), n (%)	352 (40.4)	89 (36.8)	134 (45.3)	118 (37.3)	11 (64.6)
	High LDL-C combined with elevated TG and/or decreased HDL-C, n (%)	100 (11.5)	19 (7.8)	29 (9.8)	52 (16.5)	0 (0.0)

ASCVD; Atheroscleotic cardiovascular disease, DM; Diabetes mellitus, FSR; Framingham risk score, LDL-C; Low-density lipoprotein cholesterol, TG; Triglyceride, HDL-C; High-density lipoprotein cholesterol

Table 3.

The patterns of pharmacotherapy for dyslipidemia

	Total sample, n (%)	No high-risk conditions, n (%)	High-risk conditions
			ASCVD, n (%)	DM without ASCVD, n (%)	FRS>20% without ASCVD and DM, n (%)
	(n=871)	(n=242)	(n=296)	(n=316)	(n=17)
Statin alone, n (%)	708 (81.3)	198 (81.8)	234 (79.1)	262 (82.9)	14 (82.3)
Fibrate alone, n (%)	26 (3.0)	6 (2.5)	2 (0.7)	18 (5.7)	0 (0.0)
Niacin alone, n (%)	2 (0.2)	0 (0.0)	1 (0.3)	1 (0.3)	0 (0.0)
Omega-3 fatty acid alone, n (%)	1 (0.1)	0 (0.0)	0 (0.0)	1 (0.3)	0 (0.0)
Cholesterol absorption inhibitor alone, n (%)	3 (0.3)	1 (0.4)	1 (0.3)	1 (0.3)	0 (0.0)
Statin+fibrate, n (%)	16 (1.8)	8 (3.3)	4 (1.3)	4 (1.3)	0 (0.0)
Statin+niacin, n (%)	3 (0.3)	0 (0.0)	1 (0.3)	2 (0.6)	0 (0.0)
Statin+Omega-3 fatty acid, n (%)	11 (1.3)	3 (1.2)	7 (2.4)	1 (0.3)	0 (0.0)
Statin+cholesterol absorption inhibitor, n (%)	91 (10.4)	25 (10.4)	44 (14.9)	21 (6.7)	1 (5.9)
Statin+others, n (%)	4 (0.5)	1 (0.4)	2 (0.7)	0 (0.0)	1 (5.9)
Fibrate+omega-3 fatty acid, n (%)	2 (0.2)	0 (0.0)	0 (0.0)	1 (0.3)	1 (5.9)
Fibrate+cholesterol absorption inhibitor	n (%)	0 (0.0)	0 (0.0)	4 (1.3)	0 (0.0)

ASCVD; Atherosclerotic cardiovascular disease, DM; Diabetes mellitus, FRS; Framingham risk score

Table 4.

Number of patients not at lipid goals or normal levels and mean distance to goals or normal levels

Variable		Total sample, n (%)	No high-risk conditions	High-risk conditions
Variable		Total sample, n (%)	No high-risk conditions	ASCVD	DM without ASCVD	FRS>20% without ASCVD & DM
		(n=871)	(n=242)	(n=296)	(n=316)	(n=17)
LDL-C
	No. not at goal, n (%)	179 (20.6)	34 (14.11)	57 (19.3)	85 (26.9)	3 (17.7)
	Distance to goal, mg/dL	24.2±25.1	28.2±24.2	20.7±27.5	25.0±23.9	20.2±24.9
	Mean percentage of the patients who did not reach the treatment goal	23.4%	24.0%	20.7%	25.0%	20.2%
TG
	No. not at goal, n (%)	345 (39.6)	93 (38.4)	111 (37.5)	132 (41.8)	9 (52.9)
	Distance to goal, mg/dL	71.3±86.0	64.3±66.3	77.6±105.9	70.6±79.6	76.3±89.1
	Mean percentage of the patients who did not reach the treatment goal	47.5%	42.8%	51.8%	47.1%	50.9%
HDL-C
	No. not at goal, n (%)	224 (25.7)	30 (12.4)	95 (32.1)	93 (29.4)	6 (35.3)
	Distance to goal, mg/dL	4.4±3.9	3.9±4.1	4.0±3.6	5.0±4.0	3.3±4.5
	Mean percentage of the patients who did not reach the treatmentgoal	10.9%	9.7%	10.1%	12.4%	8.3%
Non-high-density lipoprotein
	No. not at goal, n (%)	157 (18.0%)	32 (13.2%)	48 (16.2%)	75 (23.7%)	2 (11.8%)
	Distance to goal, mg/dL	23.7±19.2	23.1±16.9	30.2±21.7	19.3±16.7	44.5±36.1
	Mean percentage of the patients who did not reach treatment goal	17.8%	15.8%	23.3%	14.8%	29.2%

Table 5.

Logistic regression of attainment of lipid goals or normal levels according to individual lipid profiles

Variable	LDL-C (n=572)		TG (n=346)		HDL-C (n=172)		Non-HDL-C (n=551)
Variable	OR (95% CI)	p value	OR (95% CI)	p value	OR (95% CI)	p value	OR (95% CI)	p value
Age (per year)	0.995 (0.972-1.020)	0.716	1.010 (0.983-1.037)	0.477	0.974 (0.938-1.012)	0.178	1.007 (0.981-1.034)	0.600
Male gender	1.291 (0.793-2.103)	0.305	0.794 (0.466-1.355)	0.398	0.306 (0.122-0.766)	0.012	1.439 (0.850-2.437)	0.176
Body mass index (kg/m²)	0.933 (0.873-0.998)	0.043	0.961 (0.890-1.037)	0.309	1.004 (0.888-1.135)	0.951	0.908 (0.845-0.974)	0.007
Current smoker	0.651 (0.361-1.174)	0.154	0.491 (0.256-0.940)	0.032	0.774 (0.352-1.705)	0.525	0.665 (0.356-1.243)	0.201
Hypertension	1.736 (1.041-2.893)	0.034	0.614 (0.337-1.120)	0.112	1.086 (0.386-3.051)	0.876	2.156 (1.271-3.657)	0.004
ASCVD	0.718 (0.449-1.149)	0.167	1.186 (0.702-2.001)	0.524	1.702 (0.762-3.802)	0.194	0.586 (0.353-0.973)	0.039
DM	0.811 (0.524-1.255)	0.346	0.825 (0.520-1.309)	0.414	0.880 (0.435-1.781)	0.723	0.716 (0.453-1.134)	0.154
10-year ASCVD risk >20%	1.052 (0.489-2.263)	0.897	0.599 (0.262-1.369)	0.224	1.738 (0.678-4.458)	0.250	1.140 (0.506-2.566)	0.752

LDL-C; Low-density lipoprotein cholesterol, TG; Triglyceride, HDL-C; High-density lipoprotein cholesterol, ASCVD; Atherosclerotic cardiovascular disease, DM; Diabetes mellitus

Table 6.

Logistic regression of attainment of lipid goals in subjects with at least two abnormalities in LDL-C, triglycerides, non-HDL-C or HDL-C

Variable	OR (95% CI)	p value
Age (year)	1.000 (0.980-1.020)	0.978
Male gender	0.753 (0.498-1.138)	0.178
Body mass index (kg/m²)	0.924 (0.870-0.981)	0.009
Current smoker	0.916 (0.563-1.491)	0.724
Hypertension	1.576 (1.007-2.467)	0.046
ASCVD	0.703 (0.467-1.058)	0.091
DM	0.949 (0.657-1.371)	0.779
10-year ASCVD risk >20%	1.097 (0.592-2.033)	0.769
Fibrate use	0.468 (0.036-6.036)	0.561
Statin dose, per 20 mg	0.961 (0.791-1.167)	0.689
Baseline LDL-C, per 10 mg/dL	1.036 (0.915-1.173)	0.580
Baseline triglycerides, per 50 mg/dL	1.004 (0.893-1.130)	0.942
Baseline HDL, per 5 mg/dL	1.054 (0.972-1.142)	0.204
Baseline non-HDL-C, per 10 mg/dL	0.933 (0.824-1.057)	0.276

ASCVD; Atherosclerotic cardiovascular disease, DM; Diabetes mellitus, LDL-C; Low-lipoprotein cholesterol, HDL-C; Highlipoprotein density cholesterol

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