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American Journal of Public Health Research
DOI: 10.12691/ajphr-1-1-3

The Implementation of a Tele-Homecare System with Service Oriented Architecture and HL7 Message Transmission Standard
Ching-Sung Wang

American Journal of Medical and Biological Research
DOI: 10.12691/ajmbr-1-1-2

The Influence of Ethanol on Pyruvate Kinases Activity in Vivo, in Vitro, in Silico
Lelevich Sergey Vladimirovich, Khrustalev Vladislav Victorovich, Barkovsky Eugene Victorovich, Shedogubova Tatyana Aleksandrovna

American Journal of Medical Sciences and Medicine
DOI: 10.12691/ajmsm-1-1-1

Clinical and Histological Features in Wegener Granulomatosis
Li Cavoli Gioacchino, Passantino Rita, Bono Luisa, Tortorici Calogera, Ferrantelli Angelo, Giammarresi Carlo, Rotolo Ugo

American Journal of Infectious Diseases and Microbiology
DOI: 10.12691/ajidm-1-1-2

The Curse of Lymphatic Filariasis: Would the Continual Use of Diethylcarbamazine Eliminate this Scourge in Papua New Guinea?
Anne Lanham, Lillian Mwanri

We have released issues of some journals on February 2013.
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American Journal of Medical Sciences and Medicine
American Journal of Medical and Biological Research
American Journal of Pharmacological Sciences
American Journal of Clinical Medicine Research
American Journal of Nursing Research
American Journal of Cancer Prevention
American Journal of Medicine Studies
American Journal of Infectious Diseases and Microbiology
American Journal of Cardiovascular Disease Research
American Journal of Biomedical Research
American Journal of Mechanical Engineering
American Journal of Microbiological Research
Journal of Preventive Medicine
American Journal of Food and Nutrition
American Journal of Hypertension Research
American Journal of Sports Science and Medicine
Journal of Cancer Research and Treatment
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Journal of Biomedical Engineering and Technology
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Biomedical Science and Engineering

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Unlocking the Puzzle: Sex, Hypertension, and SGLT2 Inhibitors - Determinants of LDL-C Target Achievement in Coronary Heart Disease

Desalegn Aychiluhm Abate, Senbeta Guteta Abdissa, Zekarias Seifu Ayalew, Gebeyehu Tessema Azibte*, Zelalem Belay Ayele

Department of Internal Medicine, Addis Ababa University, College of Medicine and Health Sciences, Addis Ababa, Ethiopia

Abstract: Background: - Globally, cardiovascular diseases (CVD) are the primary cause of death. According to estimates, ischemic heart disease and cerebrovascular illnesses were responsible for 85% of 18 million CVD-related fatalities that occurred globally in 2017. One of the main causative risk factors for atherosclerotic cardiovascular disease is elevated low-density lipoprotein cholesterol (LDL-C). LDL particles can migrate from plasma into the subendothelial region of the artery, where they induce inflammation and lead to the development of atherosclerotic plaques. Thus, LDL-C lowering should be tailored to reach the target objective suggested by guidelines to reduce cardiovascular disease risk. Objective: -Assessment of low-density lipoprotein cholesterol target attainment and associated factors among patients with established coronary heart disease at the cardiology clinic, Tikur Anbessa Specialized Hospital. Methods: - Institutional-based retrospective cross-sectional study design was conducted from August 2023 to October 2023. In this study, among 240 planned participants, 221 participants were extracted, making a chart retrieval rate of 91.7%. Data analysis was done by using SPSS version 26. Multiple regression was applied to identify associated factors. Result: - In this study, about two-thirds of the participants were male, and more than one-third were between the ages of sixty-one and seventy. The level of LDL-C target attainment was 41%. The factors significantly associated with the LDL-C target attainment were male sex (AOR=1.8, 95%CI=1.44, 3.42), hypertension (AOR=0.57, 95%CI=0.31, 0.91), and taking SGLT2 inhibitors (AOR=1.5, 95%CI=1.37, 4.85). Conclusion: The level of LDL-C target attainment was low. Male sex and taking sodium-glucose transporter 2 (SGL2) inhibitors were favorable factors, but hypertension was associated with a low level of LDL target attainment.

Keywords: low-density lipoprotein, cholesterol target, coronary heart disease

Received April 28, 2024; Revised May 30, 2024; Accepted June 06, 2024

Citation: Desalegn Aychiluhm Abate, Senbeta Guteta Abdissa, Zekarias Seifu Ayalew, Gebeyehu Tessema Azibte, Zelalem Belay Ayele, Unlocking the Puzzle: Sex, Hypertension, and SGLT2 Inhibitors - Determinants of LDL-C Target Achievement in Coronary Heart Disease. American Journal of Cardiovascular Disease Research, 9 (2). 10-16. January 2024. doi:10.12691/ajcdr-9-2-1

1. Introduction

Cardiovascular diseases (CVD) are the leading cause of death globally. According to estimates, ischemic heart disease and cerebrovascular illnesses accounted for 85% of the estimated 18 million CVD-related deaths worldwide in 2017 [1]. About one-third of mortality has decreased as a result of the adoption of healthy lifestyles and pharmaceutical therapies [2,3]. CVD remains the most common cardiac condition seen by cardiologists, affecting roughly half of all heart disease patients [4].

Elevated LDL-C is a significant risk factor for atherosclerotic cardiovascular disease (ASCVD) because LDL particles can form atherosclerotic plaques, which can rupture and lead to ischemia [5,6]. In China, patients with established ASCVD are regarded as extremely high risk, with an LDL-C treatment target of below 70 mg/dL [7]. Lowering LDL-C is crucial for reducing ASCVD risk in adults. However, the recent European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS) guidelines advocate for even more aggressive goals: less than 70 mg/dL for high-risk ASCVD patients, less than 55 mg/dL for very high-risk or those with established ASCVD; and less than 40 mg/dL for very high-risk patients who have had a second vascular event within two years [8].

Despite progress in lowering LDL-C and advancing preventive measures, a significant gap remains between treatment goals and achieving LDL-C targets. [9,10,11]. In Europe, ASCVD accounts for nearly half of all deaths [12]. While managing ASCVD benefits from a long-term, team-based approach, many patients still struggle to reach their LDL-C goals [13]. This highlights the need for improvement in LDL-C management.

Global studies showed a substantial gap between LDL-cholesterol treatment goals and target achievement. The Dyslipidemia International Study (DYSIS) found that only 21.7% of 44,015 very high-risk patients in 30 countries met their LDL-C target of less than 70 mg/d [14]. Similarly, an African study reported that 71% of patients did not reach their target LDL-C levels [15].

There is a lack of data on how Ethiopian patients with established coronary heart disease achieve LDL-C goals according to recent guidelines, particularly for high-risk patients. Therefore, this study aimed to evaluate LDL-C target achievement and related factors in patients with established coronary heart disease at the cardiology clinic of Tikur Anbessa Specialized Hospital.

2. Methods and Materials

Study design

An institutional-based cross-sectional study was conducted at the cardiology clinic of Tikur Anbessa Specialized Hospital (TASH), Addis Ababa, Ethiopia, from August 01, 2023–to October 31, 2023, to assess LDL-C target attainment and associated factors among patients with established coronary heart disease. All patients with established coronary heart disease who had cardiac clinic follow-up at TASH during the study period fulfilled the inclusion criteria included in the study. Patients on Lipid-lowering drugs for less than three months and incomplete data were excluded from the study.

Sampling Determination and Sampling Procedures

All patients who fulfilled the eligibility criteria were included in the study, and there was no need for sample size calculation sampling procedures.

Operational definitions

• CHD: ACS and CCS

• ACS: STEMI, NSTEMI), or unstable angina

• CCS: Clinical diagnosis by treating cardiologist (cardiology fellow or cardiologist)

• LDL Target Attainment: We will consider patients to have achieved their LDL target if their LDL level is below 70 mg/dL after three months of statin treatment.

• Statin Therapy Intensity: Statin medications are categorized based on their expected LDL-C reduction:

™ Low-intensity: This includes daily treatment with Simvastatin 10mg, which is expected to reduce LDL-C by less than 30%.

™ Moderate-intensity: This includes daily treatment with Simvastatin 20-40mg, Atorvastatin 10-20mg, or Rosuvastatin 5-10mg, and is expected to reduce LDL-C by 30 to 50%.

™ High-intensity: This includes daily treatment with Atorvastatin 40-80mg or Rosuvastatin 20-40mg and is expected to reduce LDL-C by 50% or more.

• Smoker: history of cigarette smoking (ever smoking)

Study Procedures

The questionnaire was developed by compiling several questions from similar study materials and reviewing relevant literature and articles that could address the study's objective. A questionnaire pre-test was carried out, and modification was done based on feedback from the pre-test. The questionnaire generally included information about sociodemographic characteristics, comorbidity, concomitant drugs, and laboratory results. Data was collected from electronic medical records.

Statistical Analysis

Data was checked and cleaned for completeness and consistency, then coded, entered, and analyzed using SPSS version 26. Simple descriptive analysis was used to show the frequencies and percentages of variables. Bivariate logistic regression examined the association between independent and dependent variables. Those with a p-value less than 0.25 were transferred to multivariate logistic regression. Variables with a p-value <0.05 were declared as having statistical significance.

3. Results

Socio-demographic characteristics of the study participants

In this study, among 240 planned participants, 221 participants were extracted, making a chart retrieval rate of 91.7%. Most study participants were 61-70 years old, with a mean and SD of 59.64±10.86 years. The majority (63.3%) of the study participants were male, and only 1.3% had a smoking history, as shown in Table 1.

Table 1. Socio-demographic characteristics of the study participants with established coronary heart disease at a cardiology clinic, TASH, 2023

characteristics of coronary heart disease

In this study, 78.3% of the study participants had chronic coronary syndrome at diagnosis, 73.3% of the participants had 1-5 years duration of coronary heart disease, and 11.3% of the CHD patients had primary coronary intervention procedures, as shown in Table 2.

Table 2. The characteristics of coronary heart disease

characteristics of comorbid disease

Most (88.7%) of the study participants had comorbid disease. Of those who had the comorbid disease, 63.8% of them had hypertension, 49% of them had diabetes mellitus, 15.8% of them had CKD, and 12.8% had heart failure, as shown in Table 3.

Table 3. The comorbid disease characteristics of the study participants

4. Medications

In this study, 93.2% of the study participants took antiplatelets, and of those taking antiplatelets, 87.8% were receiving aspirin. Almost ninety-three percent of the participants received beta-blockers. Of those taking beta blockers, 76.6% used metoprolol, 93.7% of the study participants took ACEI, and 47.5% took spironolactone. Almost thirty-nine percent of the study participants took SGL2 inhibitors, 18.6% received Calcium channel blockers, and 33.5% took oral glucose-lowering agents.

Characteristics of lipid-lowering drugs

All the study participants took lipid-lowering drugs, all lipid-lowering drugs were statin, and 97.3% took atorvastatin. Ninety-two percent of the participants take a high-intensity statin, and 73.8% of the participants were taking a statin for 1-5 years (Table 4).

Table 4. Characteristics of lipid-lowering drugs

Level of LDL C target attainment after statin treatment

In this study, a lipid profile was done after 24 months of treatment for 60.2% of participants; 6.2% had ≥200 total cholesterol, and 21.3% had ≥150 triglycerides, as shown in Table 5 and Figure Overall, only 41% of patients achieved LDL-C target.

Table 5. Characteristics of the lipid profile done After Diagnosis of Coronary heart disease

Factors associated with low-density lipoprotein target attainment.

As shown in Table 6 below, the study participant’s sex, hypertension, and taking SGL2 inhibitors were associated with LDL-C target attainment on bivariate logistic regression. The multivariate logistic regression revealed that being male was associated with a1.6 1.6-fold increase in LDL-C target attainment compared to females (AOR=1.6, 95%CI=1.24, 3.42). Hypertension was associated with a 43% less likelihood of LDL-C target attainment (AOR=0.57, 95%CI=0.31, 0.91). Study participants who took SGLT2iinhibitor had a 1.5-fold increase in LDL-C target attainment compared to those not taking (AOR=1.5, 95% CI=1.37, 4.85).

Table 6. The bivariate and multivariate logistic regression of association between the independent variable and LDL-C target attainment among established coronary heart disease patients at TASH cardiac clinic, 2023

Figure 1. Time of most recent LDL determination and LDL-C target attainment

5. Discussion

This study found that the level of LDL-C target attainment was 41%. The factors significantly associated with the LDL-C target attainment were male sex (AOR=1.8, 95%CI=1.44, 3.42), hypertension (AOR=0.57, 95%CI=0.31, 0.91), and taking SGLT2 inhibitors (AOR=1.5, 95%CI=1.37, 4.85).

Hypertension, diabetes mellitus, and CKD were the most common co-morbidities in our study, similar to studies done in Kenya where hypertension, dyslipidemia, and diabetes mellitus were the most prevalent diseases among patients with coronary heart disease [16]. The difference in dyslipidemia may be because our study participants had a missing baseline lipid profile.

The finding of this study revealed that 41% of the study participants had good LDL-C target attainment. This finding was higher than the study done in the European Society of Cardiology (36.9%) [17], Thailand (27%) [18], South Africa 19 % [19], Kenya 17.1 % [16], but this is lower than the studies done in Sweden and Canada 52 % [20], Spain 56.7 % [21] and Korea [22] ,and a study done by Groenhaf et al. [23]. These differences in LDL-C target attainment rate could be due to different factors related to the study population, such as age, sex, ethnicity, and overall cardiac condition. These factors can all influence how well someone responds to treatment.

Male study participants had a 1.8-fold increase in LDL-C target attainment compared to females (AOR=1.8, 95%CI=1.44, 3.42). This finding was similar to a study done by Groenhaf et al. and a study done in China [23,24]. This may be due to the observation that LDL-C target attainment may differ between males and females in some cases and could be influenced by various factors, especially hormonal influence [25]. In other studies, statins are less effective in females than in males and are associated with more side effects and poor adherence due to the pronounced side effects. The other explanation for this unfavorable target attainment for females is that female patients have additional comorbidities than males [26].

In our study, participants with hypertension had 43% LDL-C off target compared to those patients without hypertension (AOR=0.57, 95%CI=0.31, 0.91). This finding is comparable with previous studies [19,27]. This may be due to patients with hypertension who may have metabolic syndrome with dyslipidemia. In many previous studies, hypertension and other metabolic disorders are associated with increased failure to achieve target LDL [22]. Patients with metabolic syndrome and hypertension had more difficulty achieving the target LDL levels [19]. It is more difficult to achieve target cholesterol levels, especially in patients with obesity and hypertension [28].

Our study showed that patients who took SGLT 2 inhibitors had a lower probability of achieving target LDL with an AOR of 1.5 (95% CI: 1.37, 4.85). Dapagliflozin suppresses potent atherogenic LDL-C and increases HDL-C, a favorable cardiometabolic marker. Although LDL-C levels are increased after using dapagliflozin, this was because of increased concentrations of the less atherogenic lb LDL-C. So, these failures to achieve the target number of LDL could be due to elevated 1b LDL-C [29]. SGLT2 inhibitors are effective antihyperglycemic agents by inhibiting glucose reabsorption in the kidney's proximal tubule. Besides improving glycemic control in patients with type 2 diabetes, they also have additional favorable effects, such as lowering body weight and fat [30]. Even though the exact mechanisms are unknown, recent studies suggest that SGLT-2 inhibitors could provide extra-glycemic benefits in lipid metabolism. It may pronounce lipolysis, normalizing the lipid metabolism and preventing or improving dyslipidemia [31].

Some studies showed that the achievement of target LDL could be affected by different factors such as statin dose and type, patient-related factors, provider-related factors [29]. Treating physicians and concomitant drug use while treating may affect the achievement of target LDL. In contrast, our study found that the intensity of statin was not associated with LDL target attainment.

Managing comorbidities and achieving target levels of LDL-C are crucial to managing cardiovascular health. In our study, most (88.7%) participants had comorbid disease. Of those having comorbid disease, 63.8% of them had hypertension, 49% of them had diabetes mallets, 15.8% of them had CKD, and 12.8% had heart failure; the target levels of LDL can vary based on an individual's risk factors and existing health conditions. Medical guidelines, such as those from organizations like the American College of Cardiology (ACC) and the American Heart Association (AHA), provide recommendations for LDL-C target levels based on risk categories. These guidelines are regularly updated to reflect the latest research findings. Accordingly, in these guidelines, LDL-C <70 was used for target attainment [32].

Strength and limitation

It is the first study to explore secondary LDL-C target attainment in Ethiopia. However, the retrospective nature of the study design presents a limitation. Additionally, lacking baseline LDL-C levels for most patients might inflate the target attainment rate. Finally, while the study considered LDL-C values updated within the past six months, it did not account for the specific duration of statin treatment each participant received. This lack of information could influence the interpretation of target achievement.

6. Conclusion

In this study, the level of LDL-C target attainment was 41%, which is better than the studies done in Kenya and South Africa but lower than those done in Sweden, Canada, and Spain. Factors significantly associated with LDL-C target attainment were being male (AOR=1.8, 95%CI=1.44, 3.42), and Hypertension (AOR=0.57, 95%CI=0.31, 0.91) and taking SGLT2 Inhibitors (AOR=1.5, 95%CI=1.37, 4.85).

Abbreviations

ACEI -angiotensin-converting enzyme inhibitor

ACS -acute coronary syndrome

AF -atrial fibrillation

AOR -adjusted odds ratio

ASCVD -atherosclerotic cardiovascular disease

BPH -benign prostatic hyperplasia

CCS-chronic coronary syndrome

CHD -coronary heart disease

CI -confidence interval

CKD -chronic kidney disease

COR -crude odds ratio

CVD -cardiovascular diseases

DM -diabetes mellitus

DVHD -degenerative valvular heart disease

DYSIS -Dyslipidemia International Study

EAS -European Atherosclerosis Society

ESC -European Society of Cardiology

HDL-C -high-density lipoprotein cholesterol

HIV -human immunodeficiency virus

LDL-C -low-density lipoprotein cholesterol

LV -left ventricle

NAFLD -nonalcoholic fatty liver disease

NSTEMI -non-ST-segment elevation myocardial infarction

PAD -peripheral arterial disease

PTE-pulmonary thromboembolism

SD- standard deviation

SGLT2 inhibitor -sodium-glucose cotransporter-2 inhibitor

STEMI -ST-segment elevation myocardial infarction

TASH -Tikur Anbessa Specialized Hospital

Declarations

Author Contributions: conceptualization, Methodology, Investigation, Analysis, and Writing of the manuscript- Desalegn Aychiluhm Abate, Senbeta Guteta Abdissa, Zekarias Seifu Ayalew.

Methodology, Data curation, Drafting, Interpretation, and Supervision and edition of the manuscript- Gebeyehu Tessema Azibte, Zelalem Belay Ayele.

All authors revised the manuscript and have approved the final version of the manuscript.

Funding: This research received no external funding.

Ethical Clearance

Institutional Review Board Statement: The study was conducted by the Declaration of Helsinki and approved by the Institutional Review Board of Addis Ababa University, College of Health Sciences.

Informed Consent Statement: Informed consent was obtained from all subjects involved in the study.

Data Availability Statement: The authors confirm that the data supporting the findings of this study are available within the article.

Acknowledgments: Not applicable.

Conflicts of Interest: The authors declare no conflicts of interest.

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