Statin treatment and serum low-density lipoprotein (LDL) level in the Birjand elderly dwellers: Birjand Longitudinal Aging Study (BLAS) Wave3

Abstract

Background

Elderly people have a greater risk than others to develop atherosclerotic disorders. Statins are the most efficient treatments against atherosclerosis; however, the pros and cons of the treatment should be put in balance in regard to the target level of low-density lipoprotein cholesterol (LDL-C). This study evaluates the level of LDL in the Birjand elderly population and determines the achievement of target LDL-C level, according to the American College of Cardiology (ACC) guidelines.

Methods

A retrospective observational study of statin therapy was performed from October 2018 using Birjand community health assessment data of the BLAS project. We used the 2018 ACC/AHA guidelines to determine the achievement of target LDL level in statin treated patients with clinical atherosclerotic cardiovascular diseases (ASCVD), or elderly high risk diabetic patients and dyslipidemia ones, in the Birjand elderly dwellers, stratified by statin treatment intensity. Statin and non-statin users were also compared in terms of demographic and laboratory findings. Mann-Whitney U test and Chi-Square test were used for data analysis.

Results

Out of 1418 elderly residents in this study, 683 individuals (48.2%) were male with a mean age of 69.73±7.56 years. The total mean level of LDL-C in elderly participants was 122.83±36.21 mg/dL. The mean level of LDL-C in statin use and none statin use group was 104.97±36.01 and 129.09±34.14, respectively. Only 304 (29.2%) of participants who were eligible for statin administration used the statin. While 69 (18.3%) individuals from 378 (26.7%) were using statin though they were not eligible for it. In the clinical ASCVD group, 39 (28.3%) of elderly participants achieved target LDL-C based on the ACC/AHA guideline. This was 58 (37.4%) for other participants with LDL-C ≥190 mg/dL, diabetic or participants with Framingham Risk Score (FRS) ≥10%.

Conclusions

The majority of patients who were eligible for high or moderate-intensity statin treatment had not received statin. Only one third of clinical ASCVD patients and almost half of high risk patients achieved LDL-C target values. Findings illustrate current treatment may need to be reconsidered in Birjand elderly dwellers treated with statin and physicians, should be updated on the use of statins.

Introduction

Statin therapy is the cornerstone for both primary (in patients at high risk) and secondary prevention of atherosclerotic cardiovascular diseases (ASCVD). Myocardial infarction and stroke are the leading disorders caused by atherosclerosis [1], and elderly people have a greater risk than others to develop atherosclerotic disorders. Considering the high percentage of older people in the total population, it is notable that to reduce the burden of atherosclerotic cardiovascular disease in elderly individuals. Statin treatment has shown a considerable reduction in the risk of stroke and coronary artery disease in all age groups [2].

Ideally, low density lipoprotein (LDL) cholesterol in ASCVD patients treated with statins should be less than 70 mg/dl [3]. Preferably the drugs that decrease LDL-cholesterol are rosuvastatin 20 to 40 mg and atorvastatin 40 to 80 mg. The proportion of patients with chronic atherosclerosis is increasing as the majority of the atherosclerotic events are nonfatal. Data show that in elderly subjects, a moderate dose of statin, atorvastatin, 10 to 20 mg, lovastatin, 40 mg, rosuvastatin, 5 to 10 mg, and simvastatin, 20 to 40 mg seems to be well-tolerated [4].

International guidelines are different based on the treatment strategies. In 2019, the European Society of Cardiology (ESC) presented guidelines covering indications for treatment with statins, including both primary and secondary prevention [5]. The guidelines classify patients in four categories from low to very high risk. Then, the guidelines support the determination of an appropriate treatment strategy by specifying a risk-dependent target level for LDL [6]. This specification differs from the guidelines by the American College of Cardiology (ACC) in 2018 [7] that give specific recommendations for statin treatment intensity. Based on the more recent version of ACC/AHA guidelines in 2018, achieved values of LDL-C target level were considered as LDL-C <70 mg/dL in patients with clinical ASCVD with high- intensity statin treatment protocol and LDL-C<100 mg/dL in elderly high risk diabetic patients (multiple risk factors) with high- intensity statin treatment or other diabetic patients with moderate- intensity statin treatment and dyslipidemia patients (LDL- C ≥190 mg/dL) with high- intensity statin treatment protocol. However, in patients >75 years with ASCVD, potential benefits versus adverse effects of statin therapy should be thought about before the statin initiation [8]. Little is known about the treatment strategies and the actual achievement rates of LDL targets in the Birjand elderly population. Therefore, our main goal was to determine the level of LDL in the Birjand elderly population and the achievement of the target LDL level, stratified by statin treatment intensity, in those treated with statins. We also aimed to compare the statin and non-statin treatment categories in terms of demographic, laboratory findings, or medical history and specify the number of people in the non-statin category who were eligible for the statin initiation.

Methods

Study design, setting and participants

We performed a retrospective observational study in the year 2021 (from January to September) using Birjand community health assessment electronic medical data from the BLAS (Birjand Longitudinal Aging Study) project with ethical code: IR.BUMS.Rec.1397.282 [9]. The Birjand Longitudinal Aging Study (BLAS) is a prospective study that started to enroll participants from October 2018 with rural and urban representative samples of population > 60 years. Of 1418 elderly participants who were visited for hyperlipidemia, we included 373 patients > 60 years who had already undergone statin treatment as statin and the remaining 1045 elderly participants as the non-statin study group.

The data collected included demographic information (age and sex), laboratory records (LDL-C values and other lipid variables), body mass index (BMI), medical history of chronic illnesses (diabetes, hypertension, stroke, chronic obstructive pulmonary diseases (COPD) and cancer), history of myocardial infarction or heart failure, systolic and diastolic blood pressure. We compared the statin and non-statin takers in terms of demographic, laboratory findings, and medical histories. We specified the number of people in the non-statin category who were eligible for the statin initiation and also determined the achievement of target LDL level, stratified by statin treatment intensity, in those treated with statins as below. The intensity of statin therapy was classified according to the 2018 ACC/AHA cholesterol guidelines [7]. Low-intensity statin therapy was defined as lovastatin 20 mg and simvastatin 10 mg. Moderate-intensity statin therapy was defined as atorvastatin 10 to 20 mg, lovastatin 40 mg, rosuvastatin 5 to 10 mg, and simvastatin, 20 to 40 mg. High-intensity statin therapy was defined as atorvastatin 40 to 80 mg or rosuvastatin 20 to 40 mg.

Achieved values of LDL-C target level according to the recently revised ACC/AHA guidelines were considered as LDL-C <70 mg/dl in clinical ASCVD patients with a high-intensity statin treatment protocol. The value for the elderly high risk diabetic patients (multiple risk factors) with high-intensity statin treatment protocol or others with a moderate-intensity statin treatment one, and dyslipidemia patients (LDL- C ≥190 mg/dl) with high-intensity statin treatment protocol was considered as LDL-C<100 mg/dl [10].

We used the Framingham Risk Score (FRS) to assess CVD risk in those patients who did not fall into the three mentioned categories. This model uses the variables of gender, age, smoking, diabetes, total cholesterol, and systolic blood pressure to calculate the risk. In this model individuals are classified into low-risk (<10%), moderate- risk (10-19%), relatively high-risk (20-29%), high-risk (30-39%) and very high risk (≥40%) [11]. Achieved value of LDL-C target level for both FRS>20% with high- intensity statin treatment protocol and FRS<20% with moderate-intensity statin treatment ones were considered as LDL-C<100 mg/dl as well. Atherosclerotic cardiovascular diseases (ASCVD) based on the available data defined as a history of myocardial infarction (MI), coronary artery bypass grafting (CABG), or percutaneous coronary intervention (PCI), and stroke.

Data analysis

We used SPSS (version 22) to perform the data analysis. Mann-Whitney U test and Chi-Square were applied for group comparisons. The mean ± standard deviation (SD) was used for the description of continuous variables. Qualitative variables were reported as proportion (n and %). A p-value less than 0.05 was considered significant. Since the distribution of the continuous variables based on the Kolmogorov-Smirnov test was not normal, so Mann-Whitney test was used for groups comparison.

Results

Out of 1418 elderly residents in this study, 683 individuals (48.2%) were male with a mean age of 69.73±7.56 years. The total mean level of LDL-C in elderly participants was 122.83±36.21 mg/dl. The mean level of LDL-C in the statin use and non-statin use group was 104.97±36.01 and 129.09±34.14, respectively. 180 (48.9%) of the statin users were diabetic, and 285 (76.45%) were hypertensive. 23 individuals (6.2%) had stroke, 40 (10.8%) had myocardial infarction, 79 (21.2%) had heart failure, 5 (1.3%) had COPD, and 7 (1.9%) had cancer. The comparison of the statin and non-statin users in terms of demographic, laboratory findings, and medical histories showed in Table 1.

Table 1.

Statin and non-statin users in terms of demographic, laboratory findings, and medical history

Variables	Total (n=1418)	Statin use (n=373)	Non-statin use (n=1045)	P-value
Age	69.73±7.56	69.74±7.02	69.73±7.75	0.453
Sex (male)	683 (48.2)	148 (39.7)	535 (51.2)	<0.001*
BMI (kg/m2)	26.44±5.31	27.52±5.06	26.06±5.34	<0.001*
SBP (mmHg)	131.75±20.66	132.63±19.81	131.43±20.95	0.195
DBP (mmHg)	78.35±11.46	77.88±11.10	78.52±11.59	0.449
Smoking	100 (7.1)	9 (2.4)	92 (8.8)	<0.001*
Chronic disease
Diabetes	404 (28.9)	180 (48.9)	224 (21.8)	<0.001*
Hypertension	814 (57.4)	285 (76.4)	529 (50.7)	<0.001*
Stroke	70 (5)	23 (6.2)	47 (4.5)	0.207
COPD	16 (1.1)	5 (1.3)	11 (1.1)	0.582
Cancer	28 (2)	7 (1.9)	21 (2)	0.890
MI	79 (5.7)	40 (10.8)	39 (3.8)	<0.001*
HF	163 (11.5)	79 (21.2)	84 (8)	<0.001*
Laboratory findings
Triglyceride (mg/dL)	153.38±65.71	155.36±65.60	152.69±65.76	0.379
Cholesterol (mg/dL)	197.20±41.37	178.29±41.82	203.81±39.12	<0.001*
HDL (mg/dL)	43.72±5.13	43.33±4.91	43.85±5.20	0.055
LDL (mg/dL)	122.83±36.21	104.97±36.01	129.09±34.14	<0.001*
FBS (mg/dL)	110.29±36.69	116.79±36.80	107.10±36.39	<0.001*

Mann-Whitney U test and Chi-Square test

BMI: body mass index, SBP: systolic blood pressure, DBP: diastolic blood pressure, COPD: chronic obstructive pulmonary disease, MI: myocardial infarction, HF: heart failure, HDL: high density lipoprotein, LDL: low density lipoprotein, FBS: fasting blood sugar

Missing data; BMI:1, SBP:1, DBP:1, Smoke:1, Diabetes:21, Hypertension:1, Stroke:4, COPD:6, Cancer:10, MI:21, HF=1, TG:51, LDL:51, HDL:51, Chol:52, FBS:27

Only 304 (29.2%) from 1040 (73.3%) of participants who were eligible for statin administration used the statin. While, 69 (18.3%) of participants, from 378 (26.7%), who were not eligible for statin were using the statin (Table 2).

Table 2.

Patterns of statin use and the proportion of patients in CVD risk groups

	Clinical ASCVD (n=330)	Other (n=710)	Non-Indicated (n=378)
Goal LDL (Ref)	<70	<100	-
Total LDL	108.96±36.21	129.27±37.27	122.24±30.16
Statin use	145 (43.9)	159 (22.4)	69 (18.3)
Non-statin use	185 (56.1)	551 (77.6)	309 (81.7)

ASCVD: history of myocardial infarction, coronary artery bypass grafting, percutaneous coronary intervention and stroke; Other: LDL-C ≥190 mg/l, diabetic or participants with Framingham Risk Score (FRS) ≥10%

In the clinical ASCVD group, 39 (28.3%) of elderly participants achieved target LDL-C based on the ACC/AHA guideline. This was 58 (37.4%) for other participants with LDL-C ≥190 mg/dl, diabetic, or participants with Framingham Risk Score (FRS) ≥10%. 32.6% of participants in the clinical ASCVD group, and 56.6% in the other group, were received the right intensity of statin treatment based on the ACC/AHA guideline. (Table 3).

Table 3.

The proportion of patients attaining targets for LDL according to AHA guidelines

		Clinical ASCVD (n=145)	Other (n=159)	Non-Indicated (n=69)
Goal LDL (Ref)		<70	<100	-
LDL		93.91±32.04	112.65±37.56	110.42±34.69
Achieved Target LDL (ACC/AHA Guideline)	No	99 (71.7)	97 (62.6)	-
	Yes	39 (28.3)	58 (37.4)	-
Achieved Statin Treatment Intensity (ACC/AHA Guideline)	No	97 (67.4)	69 (43.4)	-
	Yes	47 (32.6)	90 (56.6)	-

ASCVD: history of myocardial infarction, coronary artery bypass grafting, percutaneous coronary intervention and stroke; Other: LDL-C ≥190 mg/l, diabetic or participants with Framingham Risk Score (FRS) ≥10%

The proportion of participants who achieved the target level of LDL-C based on the ACC/AHA guidelines decreased by age category in patients with clinical ASCVD, elderly high risk diabetic patients (multiple risk factors) or other diabetic ones, and dyslipidemia patients (LDL- C ≥190 mg/dL). A reduction was also found in the achievement of statin treatment protocol with age (Table 4).

Table 4.

Proportion of patients attaining targets for LDL according to AHA guidelines and age category

		Clinical ASCVD (n=145)		Other (n=159)
Age		60-75	≥75	>60-75	≥75
Achieved Target LDL (ACC/AHA guideline)	No	68 (67.3)	31 (83.7)	87 (65.4)	10 (45.5)
	Yes	33 (32.7)	6 (16.2)	46 (34.6)	12 (54.5)
Achieved Statin Treatment Intensity (ACC/AHA Guideline)	No	65 (61.3)	32 (84.2)	69 (50.7)	0
	Yes	41 (38.7)	6 (15.8)	67 (49.3)	23 (100)

ASCVD: history of myocardial infarction, coronary artery bypass grafting, percutaneous coronary intervention and stroke; Other: LDL-C ≥190 mg/l, diabetic or participants with Framingham Risk Score (FRS) ≥10%

In clinical ASCVD participants target achievement rates of LDL-C (<70 mg/dl) based on the ACC/AHA guideline, were higher in males than females; specially, in the age categories of 60-65, 65-70, and 70-75 years (Fig. 1a). In other participants, includes those with LDL-C ≥190 mg/dl, diabetic, or participants with Framingham Risk Score (FRS) ≥10%, males in almost all age categories better achieved the target level of LDL-C (<100 mg/dl) based on the ACC/AHA guidelines (Fig. 1b), and this rate was not affected by age category.

Fig. 1.

LDL-C target achievement by sex and age category

Discussion

This study determined the level of LDL-C in the Birjand elderly population and the achievement of the target LDL-C level, stratified by statin treatment intensity, in those treated with statins. We also specified the number of people who were eligible for the statin initiation. Statin Therapy is the cornerstone for both primary (in patients at high risk) and secondary prevention of atherosclerotic cardiovascular diseases (ASCVD).

Findings showed that less than one third of participants who were eligible for intensive or moderate statin administration used statins. Underutilized statin treatment is common in routine care [12, 13] and may be explained by many reasons. Treatment may be discontinued in 10% of the patients for statin-related side-effects [14]. Besides, poorer patient adherence to high-intensity statin treatment was seen when compared to lower intensity one [15]. Next, physicians may not be well-updated on the use of statins. Such limitations may reduce the administration of high-intensity statins. Furthermore, only half of the patients who need high-intensity treatment perform annual LDL-C measurements [12].

Across ASCVD categories, 28.3% of participants achieved the target level of LDL-C (<70 mg/dL), which means only one third of clinical ASCVD patients achieved LDL-C target values. We also found only 36.2% of the ASCVD participants were taking statins according to the ACC/AHA cholesterol guidelines. Similarly, the target level of LDL-C achievement (<100 mg/dL) was 37.4% for other participants with LDL-C ≥190 mg/dL, diabetic or participants with Framingham Risk Score (FRS) ≥10%. These achievement rates with the more recently investigated one in Iran [16] are rather high as compared to the rates reported by other studies from several countries [12, 17–20]. Nonetheless, they still need further improvement. Underutilized statin treatment and low LDL-C measurement rates are probably reasons for not attaining the recommended treatment target values.

In accordance with prior studies [21, 22], our Findings revealed that males showed higher target achievement rates of LDL-C based on the ACC/AHA guideline than females in both clinical ASCVD and other participants with LDL-C ≥190 mg/dL, diabetic or participants with Framingham Risk Score (FRS) ≥10%. Gender gaps may be due to some beliefs or attitudes like what ethnicity imposes that act as a barrier for patient management [23, 24]. Besides, women are less likely to be adherent to their statin treatment than men, and side effects are the main reason for such non-compliance [25]. Muscle pain is one of the most common side effects of statin. New or worsening muscle symptoms are reported as the main reason for stopping statin treatment adherence among women [25].

Other findings of the study also showed that the proportion of participants who achieved the target level of LDL-C based on the ACC/AHA guideline decreased by age category in clinical ASCVD patients. This may be explained by exacerbating the physiological changes or cognitive dysfunction induced by age in these patients as they are clinically complicated. Older people may be less committed to the treatment protocol due to cognitive problems. Besides, treatment may be discontinued for statin-related side effects. This may also be the reason for less proportion of statin takers in the ASCVD participants’ ≥ 75 years based on the ACC/AHA cholesterol guidelines. Furthermore, polypharmacy is common in older adults, which increases the risk of adverse medical outcomes [26].

Our study showed several interesting findings relating to LDL target achievement. Across ASCVD categories, one third of clinical ASCVD patients achieved LDL-C target values. Similarly, the target level of LDL-C achievement (<100 mg/dL) was 37.4%. These achievement rates with the more recently investigated one in Iran [16] are rather high as compared to the rates reported by other studies from several countries [12, 17–20]. Nonetheless, they still need further improvement.

Interestingly, we found a low proportion of ASCVD patients were taking statins according to the ACC/AHA cholesterol guidelines, which may emphasize the need for physicians to be updated on the administration of statins. Finally, in accordance with previous studies [21–24], we found an under-achievement in target LDL level in females than males. Lack of analysis on the total cholesterol and HDL target values are limitations of the study, so further investigations on the target serum lipid profiles recommends.

Conclusions

The majority of patients who were eligible for high or moderate-intensity statin treatment were not received statin. Only one third of clinical ASCVD patients and almost half of high risk patients achieved LDL-C target values. Findings illustrate current treatment may need to be reconsidered in Birjand elderly dwellers treated with statin and physicians, should be updated on the use of statins.

Funding

This research was supported by Birjand University of Medical Sciences.

Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Declarations

Ethics approval and consent to participate

The study was conducted with the approval of the Ethics Committee of Birjand University of Medical Sciences (Ref: IR.BUMS.1397.282), which was gained by disclosing the research method and objectives and after obtaining written informed consent from all eligible elderly participants.

Consent for publication

N/A.

Conflict of interest

The authors declare that they have no conflict of interest.