Cardiovascular Prevention and Pharmacotherapy

Original Articles

Modifiable risk factors for coronary artery disease in the Indonesian population: a nested case-control study: Anggoro Budi Hartopo, Maria Patricia Inggriani, Brilliant Winona Jhundy, Jajah Fachiroh, Putri Tiara Rosha, Ratri Kusuma Wardani, Fatwa Sari Tetra Dewi; Cardiovasc Prev Pharmacother. 2023;5(1):24-34. Published online January 31, 2023; DOI: https://doi.org/10.36011/cpp.2023.5.e3

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Abstract PDF: Background
There is a lack of data on modifiable coronary artery disease (CAD) risk factors in the Indonesian population, hindering the implementation of assessments and prevention programs in this population. This study investigated modifiable risk factors for CAD among Indonesians by comparing them between CAD-proven patients and healthy subjects from a similar population.
Methods
In this nested, matched case-control study, the cases were patients from a referral hospital in Yogyakarta, Indonesia and the controls were respondents in a population surveillance system in Yogyakarta, Indonesia. The cases were 421 patients who had undergone coronary angiography, showing significant CAD. The sex- and age-matched controls were 842 respondents from the Universitas Gadjah Mada Health and Health and Demographic Surveillance System Sleman who indicated no CAD presence on a questionnaire. The modifiable CAD risk factors compared between cases and controls were diabetes mellitus, hypertension, central obesity, smoking history, physical inactivity, and less fruit and vegetable intake. A multivariate regression model was applied to determine independent modifiable risk factors for CAD, expressed as adjusted odds ratios (AORs).
Results
A multivariate analysis model of 1,263 subjects including all modifiable risk factors indicated that diabetes mellitus (AOR, 3.32; 95% confidence interval [CI], 2.09–5.28), hypertension (AOR, 2.52; 95% CI, 1.76–3.60), former smoking (AOR, 4.18; 95% CI, 2.73–6.39), physical inactivity (AOR, 15.91; 95% CI, 10.13–24.99), and less fruit and vegetable intake (AOR, 5.42; 95% CI, 2.84–10.34) independently and significantly emerged as risk factors for CAD.
Conclusions
Hypertension, diabetes mellitus, former smoking, physical inactivity, and less fruit and vegetable intake were independent and significant modifiable risk factors for CAD in the Indonesian population.

Changes in cardiovascular-related health behaviors during the COVID-19 pandemic: Eunji Kim, Chan-Hee Jung, Dae Jung Kim, Seung-Hyun Ko, Hae-Young Lee, Kyung-Yul Lee, Dae Ryong Kang, Sung Kee Ryu, Won-Young Lee, Eun-Jung Rhee, Hyeon Chang Kim; Cardiovasc Prev Pharmacother. 2023;5(1):15-23. Published online January 27, 2023; DOI: https://doi.org/10.36011/cpp.2023.5.e2

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Abstract PDF Supplementary Material: Background
The COVID-19 pandemic has been the most pressing health challenge in recent years. Meanwhile, prevention for other diseases, such as cardiovascular disease (CVD) has been less prioritized during the pandemic. COVID-19, a novel infectious disease, both had a direct impact on public health and provoked changes in health-related behaviors, including those for CVD prevention. This study sought to examine changes in CVD-related health behaviors during the COVID-19 pandemic and related sociodemographic factors.
Methods
We used data from the Cardiovascular Disease Prevention Awareness Survey conducted in Korea in June 2022. A total of 2,000 adults across Korea’s 17 provinces completed a structured questionnaire online or on a mobile device. Self-reported changes in CVD-related health behaviors were investigated. We used unadjusted and adjusted logistic regression models to explore the associations between negative changes and sociodemographic factors.
Results
In smoking, drinking, and healthcare service use, the proportion of those with positive changes surpassed the proportion of respondents who reported negative changes. In contrast, negative changes predominated for diet, exercise, and stress. Most individuals (52.6%) reported a deterioration of psychological distress. These negative changes were significantly associated with age, sex, marital status, and the presence of cardiometabolic disease.
Conclusions
The COVID-19 pandemic has affected CVD-related health behaviors. Based on these changes, CVD prevention should be encouraged with appropriate and prioritized strategies.

Review Article

Adverse reactions to antiarrhythmic drugs: Ungjeong Do; Cardiovasc Prev Pharmacother. 2023;5(1):1-14. Published online January 16, 2023; DOI: https://doi.org/10.36011/cpp.2023.5.e1

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Abstract PDF: There are various types of adverse reactions to antiarrhythmic drugs (AADs). Proarrhythmia, which refers to an exacerbation of the preexisting arrhythmia or occurrence of a new arrhythmia, may occur under the therapeutic concentration of an AAD. Bradyarrhythmia is the most common type of proarrhythmia due to AADs, and prior myocardial infarction and old age are known risk factors. Atrial flutter with 1:1 atrioventricular conduction usually occurs during rhythm control of atrial fibrillation with class IC AADs. QT prolongation due to AADs, mainly class III AADs, elevates the risk of torsade de pointes by triggered activity due to early afterdepolarization. The addition of clinical factors that promote QT prolongation, such as hypokalemia, hypomagnesemia, female sex, and bradycardia, increases the risk of developing torsade de pointes. Proarrhythmic monomorphic ventricular tachycardia usually occurs as a result of slow conduction and disparity of refractoriness due to class IC AADs. In patients with preexisting left ventricular systolic dysfunction or structural heart disease, the risk of hypotension or cardiogenic shock caused by negative inotropic effects due to AADs should be considered. To prevent these major adverse reactions to AADs, we need to understand the electrophysiologic properties of AADs in detail. Furthermore, the risk of proarrhythmia could be heightened by interplay with clinical factors, such as electrolyte unbalances, heart rate, and hepatic/renal or myocardial dysfunction. Sufficient awareness about drug-drug interactions, which may affect the metabolism of AADs, will improve patient safety during the management of arrhythmia.

Original Article

Public awareness of cardiovascular disease prevention in Korea: Eunji Kim, Chan-Hee Jung, Eun-Jung Rhee, Junghyun Noh, Jae Hyuk Lee, Hun-Jun Park, Sungha Park, Sang-Hyun Ihm, Won-Young Lee, Hyeon Chang Kim; Cardiovasc Prev Pharmacother. 2022;4(4):149-157. Published online October 26, 2022; DOI: https://doi.org/10.36011/cpp.2022.4.e20

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Abstract PDF Supplementary Material: Background
The burden of cardiovascular disease (CVD) is significant in Korea. Ultimately, public knowledge and awareness of CVD risk factors and prevention are essential to reduce its burden. Hence, this study aimed to examine the level of public awareness of CVD risk factors and prevention in Korea in 2022.
Methods
We used data from the Cardiovascular Disease Prevention Awareness Survey conducted by the Korean Society of Cardiovascular Disease Prevention in June 2022. Using a structured web-based questionnaire, 2,000 individuals aged 20 years or more were surveyed on computers or mobile devices. Information on sociodemographic characteristics, the presence of cardiometabolic disease, CVD concerns and self-assessed likelihood, and awareness of CVD prevention were analyzed.
Results
Cancer (44.3%) was the most feared disease, followed by CVD (19.5%). Nevertheless, most respondents stated that they were likely to develop CVD in their lifetime (67.4%). Only 9.2% of respondents were aware of the details of recommendations to prevent CVD, and this level of knowledge was also low among respondents with cardiometabolic diseases (10.7%). Not smoking, being physically active, eating a healthy diet, and reducing alcohol consumption were deemed easy to implement. On the contrary, reducing stress, being physically active, and eating a healthy diet were considered the most difficult recommendations to practice.
Conclusions
Public awareness of CVD risk factors and prevention appeared to be insufficient in Korea. Our research suggests that simple but practical recommendations should be conveyed and promoted to raise public awareness, which is currently inadequate.

Review Articles

Metabolically healthy obesity: it is time to consider its dynamic changes: Yun Kyung Cho, Chang Hee Jung; Cardiovasc Prev Pharmacother. 2022;4(4):123-131. Published online October 24, 2022; DOI: https://doi.org/10.36011/cpp.2022.4.e19

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Abstract PDF: Obesity reduces life expectancy, lowers quality of life, and causes numerous cardiometabolic diseases and some cancers. However, the individual risk of developing obesity-associated comorbidities is highly variable and cannot be explained only by body mass index. Observations that some obese people have a low risk for cardiometabolic disorders gave rise to the notion of metabolically healthy obesity (MHO). Despite the lack of a precise definition, MHO is typically identified by normal glucose and lipid metabolism indices, as well as the absence of hypertension. In individuals with MHO, the absence of metabolic abnormalities may minimize the risk of mortality, cardiovascular diseases, chronic kidney disease, dementia, and cancer, compared to metabolically unhealthy individuals with obesity. However, MHO appears to be a temporary phenotype that may not confer permanent benefits to individuals with obesity, further justifying therapeutic efforts to maintain metabolic fitness. In this review, we describe the traits of the MHO phenotype, its changeable nature, and the factors associated with phenotype change. In addition, we discuss the clinical outcomes of the MHO phenotype, particularly focusing on the transition of metabolic health over time and its effect on cardiometabolic disorders. Finally, the clinical importance of maintaining metabolic health is emphasized.

The effects and side effects of liraglutide as a treatment for obesity: Jeonghoon Ha, Jin Yu, Joonyub Lee, Hun-Sung Kim; Cardiovasc Prev Pharmacother. 2022;4(4):142-148. Published online October 20, 2022; DOI: https://doi.org/10.36011/cpp.2022.4.e18

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Abstract PDF: The incidence of obesity is increasing throughout the world, including Korea. Liraglutide, the main purpose of which is glucose control, has recently gained significant attention due to its additional effect on weight loss. Liraglutide injections have been widely used as an important treatment for obese patients in Korea. In addition to weight loss, liraglutide has various other effects, such as prevention of cardiovascular disease. Despite its excellent effect on weight loss, notable side effects, such as nausea and vomiting, have also been associated with liraglutide. Despite these side effects, liraglutide has not been discontinued due to its beneficial effects on weight loss. Nonetheless, there are reports wherein patients did not experience weight loss upon taking the drug. As such, there is a possibility of liraglutide misuse and abuse. Therefore, physicians need to have a broad understanding of liraglutide and understand the advantages and disadvantages of liraglutide prescription.

The crosstalk between insulin resistance and nonalcoholic fatty liver disease/metabolic dysfunction-associated fatty liver disease: a culprit or a consequence?: Dae-Jeong Koo, Won-Young Lee; Cardiovasc Prev Pharmacother. 2022;4(4):132-141. Published online October 20, 2022; DOI: https://doi.org/10.36011/cpp.2022.4.e17

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Abstract PDF: Nonalcoholic fatty liver disease (NAFLD), which has recently undergone a change in its definition and acronym to “metabolic dysfunction associated fatty liver disease (MAFLD),” is clinically significant as an increasingly prevalent independent risk factor for cardiovascular diseases. Insulin resistance is considered to be a key mechanism in the development and progression of NAFLD/MAFLD, and fatty liver disease itself may exacerbate insulin resistance. In this review, we describe the mechanisms underlying the interaction between insulin resistance and fatty liver, and we summarize the therapeutic attempts based on those mechanisms.

Blood pressure control in hypertensive disorders of pregnancy: Helsi Rismiati, Hae-Young Lee; Cardiovasc Prev Pharmacother. 2022;4(3):99-105. Published online July 29, 2022; DOI: https://doi.org/10.36011/cpp.2022.4.e16

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Abstract PDF

Hypertension is a major cause of maternal morbidity and occurs as a complication in up to one in ten pregnancies. Hypertensive disorders of pregnancy encompass gestational hypertension, preeclampsia, chronic hypertension, and chronic hypertension with superimposed preeclampsia. However, the management of hypertensive disorders of pregnancy remains a matter of debate, particularly the blood pressure thresholds and targets for managing hypertension in pregnancy. Previously, there was no clear evidence of the effectiveness of aggressive blood pressure control in pregnancy due to the risk of fetal growth restriction. Recent clinical trials have shown that aggressive control of blood pressure in pregnant women is safe for both the mother and fetus. The purpose of this paper is to present a clinically oriented guide to the drugs of choice in patients with hypertension during pregnancy, present contrasts among different guidelines and recent clinical trials, and discuss the blood pressure thresholds and targets for hypertension during pregnancy based on recent studies.

Citations

Citations to this article as recorded by

Combined Effects of Methyldopa and Baicalein or Scutellaria baicalensis Roots Extract on Blood Pressure, Heart Rate, and Expression of Inflammatory and Vascular Disease-Related Factors in Spontaneously Hypertensive Pregnant Rats
Michał Szulc, Radosław Kujawski, Przemysław Ł. Mikołajczak, Anna Bogacz, Marlena Wolek, Aleksandra Górska, Kamila Czora-Poczwardowska, Marcin Ożarowski, Agnieszka Gryszczyńska, Justyna Baraniak, Małgorzata Kania-Dobrowolska, Artur Adamczak, Ewa Iwańczyk-S
Pharmaceuticals.2022; 15(11): 1342. CrossRef

Original Article

Effect of the addition of thiazolidinedione to sodium-glucose cotransporter 2 inhibitor therapy on lipid levels in type 2 diabetes mellitus: a retrospective study using Korean National Health Insurance Service data: Taegyun Park, Kyungdo Han, Dongwook Shin, Jongho Park; Cardiovasc Prev Pharmacother. 2022;4(3):114-122. Published online July 29, 2022; DOI: https://doi.org/10.36011/cpp.2022.4.e15

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Abstract PDF: Background
Dyslipidemia is common in patients with type 2 diabetes mellitus (T2D) and contributes to an increased risk of cardiovascular disease. Previous studies have shown that treatment with thiazolidinediones (TZDs) and sodium-glucose cotransporter-2 inhibitors (SGLT2-i) may help to improve dyslipidemia in T2D patients. In this study, we investigated whether patients treated with TZD and SGLT2-i showed greater improvement in high-density lipoprotein cholesterol (HDL-C) levels than those treated with only SGLT2-i.
Methods
From the National Health Insurance Service database of Korea, we extracted all patients who first received SGTL2-i from 2014 to 2016. Propensity score matching was performed to balance the two groups: group A (SGTL2-i and TZD, regardless of other antidiabetic medications) and group B (SGTL2-i only without TZD, regardless of other antidiabetic medications). Posttreatment HDL-C levels were compared by the Student t-test.
Results
In total, 1,400 T2D patients (700 in each group) were matched by propensity score matching. There was a significant posttreatment increase in HDL-C in group A (49.54±20.03 to 51.6±12.92 mg/dL, P=0.007), but not in group B (49.14±13.52 to 49.1±2.15 mg/dL, P=0.937). Group A also showed significantly higher posttreatment HDL-C levels than group B (51.4±12.92 vs. 49.1±12.15 mg/dL, P<0.001). Regarding the secondary endpoints, posttreatment triglyceride levels were lower (P<0.001), but total cholesterol (P=0.131) and low-density lipoprotein cholesterol levels (P=0.054) were not different after treatment.
Conclusions
The combination of SGTL2-i and TZD may be more effective in ameliorating dyslipidemia in T2D patients than SGLT2-i alone. However, further studies are needed to confirm this finding.

Review Articles

Cardiovascular diseases in HIV patients: Hyun-Ha Chang; Cardiovasc Prev Pharmacother. 2022;4(3):95-98. Published online July 29, 2022; DOI: https://doi.org/10.36011/cpp.2022.4.e14

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Abstract PDF: New and more effective antiretroviral therapy regimens have increased viral suppression and improved immune function recovery, leading to the extension of the lifespan of people living with HIV (PLWH). The extended lifespan of PLWH has recently been reported as a significant factor associated with diabetes mellitus, dyslipidemia, and long-term metabolic consequences, such as cardiovascular diseases. Therefore, this article briefly reviews the epidemiology and risk factors of cardiovascular diseases, including dyslipidemia and diabetes mellitus, in PLWH.

Severe hypoglycemia as a risk factor for cardiovascular outcomes in patients with type 2 diabetes: is it preventable?: Seung-Hyun Ko; Cardiovasc Prev Pharmacother. 2022;4(3):106-113. Published online July 29, 2022; DOI: https://doi.org/10.36011/cpp.2022.4.e13

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Abstract PDF: Hypoglycemia in people with type 2 diabetes mellitus (T2DM) is troublesome and an important barrier to diabetes management. Although more intensive glycemic control is emphasized to prevent diabetes-related long-term complications, it raises the risk of hypoglycemia in people with T2DM. Severe hypoglycemia (SH), defined as critical events characterized by altered mental and/or physical status requiring assistance for recovery, is considered an advanced and life-threatening form of hypoglycemia. The detection of SH is an important issue because it is associated with further adverse clinical outcomes such as cardiovascular events, mortality, cognitive impairment, and decreased quality of life. By identifying the potential risk factors for SH and introducing measures to minimize SH, SH itself and subsequent harmful clinical outcomes could be prevented in people with T2DM. The traditional risk factors for SH in T2DM, such as older age, long-standing diabetes with decreased insulin secretion, advanced vascular complications, serious comorbidities, and insulin use, are usually unmodifiable. However, unhealthy lifestyle factors, defined as current smoking, heavy alcohol consumption, and lack of regular exercise, can be improved through active patient education. In recent research, greater adherence to healthy lifestyle factors and any improvement in unhealthy lifestyle habits were found to be associated with a substantially lower risk of SH in individuals with T2DM. As well as being an essential component of diabetes self-care and optimal glycemic control, lifestyle modification probably contributes to the prevention of SH in individuals with T2DM.

Original Article

Development of a predictive model for the side effects of liraglutide: Jiyoung Min, Jiwon Shinn, Hun-Sung Kim; Cardiovasc Prev Pharmacother. 2022;4(2):87-93. Published online April 27, 2022; DOI: https://doi.org/10.36011/cpp.2022.4.e12

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Abstract PDF Supplementary Material

Background
Liraglutide, a drug used for the management of obesity, has many known side effects. In this study, we developed a predictive model for the occurrence of liraglutide-related side effects using data from electronic medical records (EMRs).
Methods
This study included 237 patients from Seoul St. Mary's Hospital and Eunpyeong St. Mary's Hospital who were prescribed liraglutide. An endocrinologist obtained medical data through an EMR chart review. Model performance was evaluated using the mean of the area under the receiver operating characteristic curve (AUROC) with a 95% confidence interval (CI).
Results
A predictive model was developed for patients who were prescribed liraglutide. However, 37.1% to 75.5% of many variables were missing, and the AUROC of the developed predictive model was 0.630 (95% CI, 0.551–0.708). Patients who had previously taken antiobesity medication had significantly fewer side effects than those without previous antiobesity medication use (20.7% vs. 41.4%, P<0.003). The risk of side effect occurrence was significantly higher in patients with diabetes than in patients without diabetes by 2.389 times (odds ratio, 2.389; 95% CI, 1.115–5.174).
Conclusions
This study did not successfully develop a predictive model for liraglutide-related side effects, primarily due to issues related to missing data. When prescribing antiobesity drugs, detailed records and basic blood tests are expected to be essential. Further large-scale studies on liraglutide-related side effects are needed after obtaining high-quality data.

Citations

Citations to this article as recorded by

The effects and side effects of liraglutide as a treatment for obesity
Jeonghoon Ha, Jin Yu, Joonyub Lee, Hun-Sung Kim
Cardiovascular Prevention and Pharmacotherapy.2022; 4(4): 142. CrossRef

Review Articles

Obesity and heart failure with preserved ejection fraction: pathophysiology and clinical significance: Da Young Lee; Cardiovasc Prev Pharmacother. 2022;4(2):70-74. Published online April 27, 2022; DOI: https://doi.org/10.36011/cpp.2022.4.e10

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Abstract PDF: Obesity is a risk factor for heart failure and cardiovascular disease. Of particular note, over 80% of patients with heart failure with a preserved ejection fraction (HFpEF) are overweight or obese. In this study, we aimed to review the association between obesity and HFpEF. Obese patients with HFpEF exhibit a distinct phenotype. In addition to impaired left ventricular (LV) diastolic function and high filling pressures, obese patients with HFpEF possess other factors that cause elevated LV filling pressure, such as a greater dependence on plasma volume expansion, aggravated pericardial restraint, and increased ventricular interaction. Obesity can contribute to HFpEF through hemodynamic, neurohormonal, inflammatory, and mechanical mechanisms. An increased amount of body fat can induce plasma volume expansion, resulting in chamber remodeling, pericardial restraint, and ultimately elevations in LV filling pressure. Obesity can mediate the activation of sympathetic nervous system signaling and the renin-angiotensin-aldosterone system. These unique pathophysiological characteristics of individuals with both obesity and HFpEF suggest that obesity with HFpEF can be considered a specific phenotype. Future research is expected to clarify effective treatment modalities for obesity-related HFpEF.

Targets for rescue from fatty acid-induced lipotoxicity in pancreatic beta cells: Seok-Woo Hong, Won-Young Lee; Cardiovasc Prev Pharmacother. 2022;4(2):57-62. Published online April 26, 2022; DOI: https://doi.org/10.36011/cpp.2022.4.e9

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Abstract PDF: A persistent intake of excess calories increases plasma levels of free fatty acids, particularly the saturated form that has been shown to exert toxic effects on pancreatic beta cells by inducing dysfunction and apoptosis (i.e., lipotoxicity). An insufficient supply of insulin due to beta cell failure is a major factor in the onset and progression of type 2 diabetes; therefore, it is crucial to understand the cellular mechanisms of lipotoxicity to prevent beta cell failure. Many studies on the effects of lipotoxicity have demonstrated the various factors responsible for beta cell impairment, but the mechanisms of dysfunction and apoptosis resulting from lipotoxicity have not been fully described. This review discusses lipotoxicity-induced alterations of cellular mechanisms, and assesses drugs such as incretin mimetics, thiazolidinedione, and clusterin. Understanding the molecular mechanisms of lipotoxicity-induced beta cell failure is useful in guiding the development of new therapeutic targets for diabetes treatment.

De-escalation strategies of dual antiplatelet therapy in patients undergoing percutaneous coronary intervention for acute coronary syndrome: Young Bin Song; Cardiovasc Prev Pharmacother. 2022;4(2):63-69. Published online April 26, 2022; DOI: https://doi.org/10.36011/cpp.2022.4.e11

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Abstract PDF: Antiplatelet therapy is important for reducing systemic and local thrombotic events in patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS). Antiplatelet treatment regimens, along with dual antiplatelet therapy consisting of aspirin and a P2Y12 inhibitor for patients receiving PCI, have frequently changed over the years. With improvements in the understanding of the prognostic relevance of bleeding events in patients with PCI, as well as the safety and efficacy of drug-eluting stents, several randomized controlled trials (RCTs) have been conducted on antiplatelet treatment strategies associated with a more favorable balance between ischemic and bleeding risks. Several key RCTs for appropriate antiplatelet therapy in patients receiving PCI for ACS have been reported, and practical guidelines have been updated. This manuscript presents the results of major RCTs on de-escalation strategies of dual antiplatelet treatment in patients receiving PCI for ACS.

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