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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 PDFSupplementary 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.
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.
Original Article
Effects of exercise on reducing diabetes risk in Korean women according to menopausal status
Jung-Hwan Cho, Hye-Mi Kwon, Se-Eun Park, Ju-Hwan Yoo, Kyung-Do Han, Eun-Jung Rhee, Won-Young Lee
Cardiovasc Prev Pharmacother. 2022;4(2):75-86.   Published online April 21, 2022
DOI: https://doi.org/10.36011/cpp.2022.4.e8
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Abstract PDF
Background
Exercise and estrogen play key roles in preventing diabetes and obesity. Women’s risk of diabetes could increase due to the loss of the protective effect of estrogen after menopause. Therefore, we investigated the relationship of the intensity and frequency of exercise with diabetes risk in Korean women.
Methods
Hazard ratios (HRs) for the development of diabetes were analyzed in 926,807 premenopausal and 1,188,346 postmenopausal women without diabetes over the age of 40 who underwent the Korean National Health Examination in 2009 and were followed up until 2018. The number of days of physical activity according to exercise intensity and metabolic equivalent of task-minutes per week (MET-min/wk) were calculated.
Results
In total, 38,096 premenopausal (4.1%) and 120,605 postmenopausal (10.2%) women were newly diagnosed with diabetes. Regardless of menopausal history, the risk of diabetes was significantly lower in groups with higher MET-min/wk than in sedentary participants (0 MET-min/wk, reference), although this effect disappeared in postmenopausal women with the highest level of MET-min/wk (MET-min/wk ≥1,500) after adjusting for all variables (HR, 1.0; 95% confidence interval, 0.97–1.02). Participants who exercised for more than 1 day per week had a significantly lower risk of diabetes, regardless of the intensity. However, this benefit was lost in women with near-daily exercise (≥6 days/wk).
Conclusions
Exercise was effective in preventing diabetes in both premenopausal and postmenopausal women. A moderate amount of exercise should be actively encouraged to lower the risk of diabetes in women, especially after menopause, while simultaneously considering the insignificant benefits of excessive exercise.
Review Article
Polygenic risk score: a useful clinical instrument for disease prediction and risk categorization
Jae-Seung Yun
Cardiovasc Prev Pharmacother. 2022;4(1):13-17.   Published online January 21, 2022
DOI: https://doi.org/10.36011/cpp.2022.4.e7
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Abstract PDF
Genetic information is one of the essential components of precision medicine. Over the past decade, substantial progress has been made, such as low-cost, high-throughput genotyping arrays, advances in statistical techniques, and progressively larger discovery datasets, enabling the discovery of alleles contributing to common diseases, such as coronary artery disease and type 2 diabetes. The polygenic risk score (PRS) represents the aggregate contribution of numerous common genetic variants, individually conferring small to moderate effects, and can be used as a marker of genetic risk for major chronic diseases. PRSs can be obtained from early childhood, and only one measurement is needed to determine the score. PRSs can potentially be used for triage of further investigations to confirm disease susceptibility and to optimize individualized preventive strategies for high-risk disease groups. We provide an overview and commentary on important advances in deriving and validating PRSs, as well as the implementation of PRSs for clinically useful purposes.
Original Article
Safety and efficacy of low-dose aspirin in patients with coronary artery spasm: long-term clinical follow-up
Byoung Geol Choi, Kyung-Hee Kim, Seung-Woon Rha
Cardiovasc Prev Pharmacother. 2022;4(1):26-33.   Published online January 21, 2022
DOI: https://doi.org/10.36011/cpp.2022.4.e6
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Abstract PDF
Background
Aspirin is known to aggravate coronary artery spasm (CAS) regardless of the dose (100–325 mg/day). However, it is unclear whether low-dose aspirin (LDA; 100 mg) has deleterious impacts on the clinical course of CAS patients in the long-term. Thus, we investigated the impact of LDA on the long-term clinical outcomes of CAS patients.
Methods
A total of 5,697 consecutive patients without significant coronary artery disease who underwent an acetylcholine provocation test from November 2004 to May 2015 were enrolled. Of these patients, 3,072 CAS patients were enrolled in the study and divided into two groups based on whether they took LDA: the LDA group (n=338) and the non-LDA group (n=2,734). All CAS patients were prescribed anti-anginal medication as appropriate. To adjust for any potential confounders that could cause bias, a propensity score matching analysis was performed using a logistic regression model.
Results
After propensity score matching, two propensity-matched groups (524 pairs, 1,048 patients, C-statistic=0.827) were generated, and the baseline characteristics of the two groups were balanced. The two groups were showed no significant differences in any follow-up events, such as major adverse cardiac events and recurrent angina.
Conclusions
The main finding of the present study is that the use of LDA did not affect cardiovascular events up to 5 years in CAS patients. Therefore, the prescription of LDA in these patients should be individualized considering their clinical status.
Review Articles
Anti-inflammatory effects of colchicine on coronary artery disease
Hun-Jun Park
Cardiovasc Prev Pharmacother. 2022;4(1):7-12.   Published online January 20, 2022
DOI: https://doi.org/10.36011/cpp.2022.4.e5
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Abstract PDF
Inflammation plays a crucial role in the pathophysiology of coronary artery disease (CAD). Several types of sterile inflammation are mediated through the nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 (NLRP3) inflammasome. Colchicine has recently been shown to effectively block NLRP3 inflammasome assembly in addition to several other actions on inflammatory cells. Recent evidence also points to favorable effects of colchicine in patients with CAD, including lower levels of inflammatory markers, coronary plaque stabilization, and more favorable cardiac recovery after injury. This review focuses on the role of colchicine in the process of atherosclerosis and discusses its potential as a therapeutic option for the prevention and treatment of CAD.
Adverse effects of statin therapy and their treatment
Dae Young Cheon, Sang-Ho Jo
Cardiovasc Prev Pharmacother. 2022;4(1):1-6.   Published online January 20, 2022
DOI: https://doi.org/10.36011/cpp.2022.4.e4
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Abstract PDF
Statins are one of the most widely used drugs worldwide as first-line drugs for the treatment of hyperlipidemia and the prevention and treatment of cardiovascular diseases. Most of the side effects of statins are known to be mild, and mainly hepatotoxicity and various muscle symptoms are known. Recently, there have been studies on concerns about an increase in the incidence of diabetes after using statins, but it was found that the benefits sufficiently outweigh the risk of side effects. Therefore, the use of statins in the appropriate group should be actively performed, and it seems that the side effects can be prevented through close physical observation and appropriate examination.
Original Articles
Effects of physical activity on cardiovascular outcomes and mortality in Korean patients with diabetes: a nationwide population-based cohort study
Inha Jung, Sun Joon Moon, Hyemi Kwon, Se Eun Park, Kyung-Do Han, Eun-Jung Rhee, Won-Young Lee
Cardiovasc Prev Pharmacother. 2022;4(1):42-55.   Published online January 20, 2022
DOI: https://doi.org/10.36011/cpp.2022.4.e3
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Abstract PDFSupplementary Material
Background
Since a sedentary lifestyle is considered a modifiable risk factor for cardiovascular disease (CVD), physical activity (PA) is recommended for type 2 diabetes mellitus (T2DM) patients to prevent CVD. We investigated the association between different levels of PA and the risk for CVD and all-cause mortality in patients with T2DM using nationwide data.
Methods
We examined health examination data and claims records of 2,745,637 participants with T2DM at baseline from the Korean National Health Insurance Service who underwent health examinations between 2009 and 2012. We excluded subjects with a history of myocardial infarction or stroke. Each participant was asked to report their weekly PA levels according to three categories: vigorous, moderate, and walking. The incidence of CVD and death was analyzed until 2017.
Results
The risk of CVD was lower in regular exercisers than in nonexercisers after adjusting for confounding variables. A dose-response trend was evident in the association between the degree of PA and CVD risk. All categories of PA were inversely associated with CVD risk and mortality. The reduction in CVD risk and all-cause mortality was more profound in patients aged ≥65 years.
Conclusions
Augmenting PA might have positive effects on the prevention of CVD and all-cause death, especially in the elderly. The benefits of PA were consistently observed in various subgroups regardless of the presence of chronic conditions. Therefore, clinicians should encourage elderly patients with T2DM to increase their daily PA.
Association between reproductive aging and hypertension among Korean women
Eunji Kim, Youngrong Lee, Hyeon Chang Kim
Cardiovasc Prev Pharmacother. 2022;4(1):34-41.   Published online January 19, 2022
DOI: https://doi.org/10.36011/cpp.2022.4.e2
  • 575 View
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Abstract PDFSupplementary Material
Background
Although postmenopausal women are well known to have a high prevalence of hypertension, it is unclear whether menopause itself increases blood pressure independently from the known risk factors of hypertension. This study sought to determine whether an association exists between reproductive aging, analyzed as a gradual transition, and an increased risk of hypertension among Korean women.
Methods
This cross-sectional study used baseline data from 5,456 women aged 30 to 64 years who participated in the Cardiovascular and Metabolic Diseases Etiology Research Center study in Korea from 2013 to 2018. The participants’ stage of reproductive aging was assessed by a questionnaire and categorized as premenopause, perimenopause, and postmenopause. Multiple logistic regression models were used to analyze the association between menopausal status and hypertension after adjusting for age, education level, marital status, employment, household income, smoking, drinking, physical activity, body mass index, and hormone replacement therapy use.
Results
The prevalence of hypertension increased with reproductive aging: 9.8% in premenopause, 25.2% in perimenopause, and 27.7% in postmenopause. The adjusted odds ratio (95% confidence interval) for having hypertension was 1.70 (1.07–2.72) for perimenopausal women and 1.14 (0.88–1.48) for postmenopausal women, compared to premenopausal women.
Conclusions
Our study shows that perimenopausal women are at high risk of developing hypertension. Since the menopausal transition may last months or years, blood pressure monitoring and early interventions are crucial for not only postmenopausal women, but also those in the transition.
Indirect comparison of nonvitamin K oral anticoagulants and left atrial appendage occlusion
Sung-Hwan Kim, So-Yoon Park, Seung-Sik Hwang
Cardiovasc Prev Pharmacother. 2022;4(1):18-25.   Published online January 18, 2022
DOI: https://doi.org/10.36011/cpp.2022.4.e1
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Abstract PDFSupplementary Material
Background
Anticoagulation is important in atrial fibrillation (AF) patients to reduce the occurrence of thrombotic events. We evaluated the efficacy and safety of percutaneous left atrial appendage occlusion (LAAO) as an alternative to systemic anticoagulation through an indirect comparative analysis.
Methods
An indirect comparative analysis of nonvitamin K oral anticoagulants (NOACs) and LAAO was conducted. Comparisons were made using data from four landmark randomized clinical trials (RE-LY, ROCKET-AF, ARISTOTLE, and PROTECT AF). Using warfarin as the common comparator, an indirect comparison was performed using data from each trial, and the relative risk was calculated between NOACs and LAAO.
Results
NOACs and LAAO showed similar results for the reduction of stroke and systemic embolism, with a non-statistically significant trend favoring NOACs (hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.37–1.46 for dabigatran; HR, 0.99; 95% CI, 0.50–1.92 for rivaroxaban; HR, 0.89; 95% CI, 0.45–1.74 for apixaban). Significantly fewer major bleeding and procedure-related complications were found in patients treated with apixaban compared with LAAO (HR, 0.45; 95% CI, 0.26–0.75). Cardiovascular death occurred more frequently in patients administered NOACs than in patients with LAAO (HR, 2.28; 95% CI, 1.03–5.10 for dabigatran; HR, 2.41; 95% CI, 1.09–5.42 for rivaroxaban; HR, 2.40; 95% CI, 1.10–5.36 for apixaban).
Conclusions
The rate of all-cause death was similar between NOACs and LAAO. Compared with LAAO, NOACs led to a nonsignificant numerical decrease in stroke and embolism in AF patients. Significantly fewer safety events occurred in patients treated with apixaban. LAAO significantly reduced cardiovascular death.
Association between Myocardial Infarction Location and In-Hospital Mortality in Iran: A Nationwide Study
Mohammad Shahbaz, Seyed Saeed Hashemi Nazari, Amineh Salehipour, Roya Karimi
Cardiovasc Prev Pharmacother. 2021;3(4):124-133.   Published online October 31, 2021
DOI: https://doi.org/10.36011/cpp.2021.3.e16
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Abstract PDF
Background
Myocardial infarction (MI) is one of the most important health problems in the world, including Iran. The rate of in-hospital mortality in MI patients ranges from 7.7% to 19.2% in different countries. Despite the promotion and utilization of new therapeutic approaches, MI-related morbidity and mortality have remained high . The recognition of risk factors for MI-related mortality plays an important role in reducing post-MI mortality.
Methods
In this study, we used national MI registry data. In total, 33,831 patients who had been hospitalized in the coronary care unit of Iranian hospitals from 2012 to 2014 were analyzed. Using multivariable logistic regression, we estimated the impact of various risk factors on in-hospital mortality after MI.
Results
The in-hospital mortality rate in patients with ST-elevation MI was higher than that of patients with non–ST-elevation MI. In-hospital mortality was most strongly associated with left-location MI (odds ratio [OR] relative to the non-ST-elevation MI group, 2.15), in comparison with middle-location MI (OR, 1.47) and right-location MI (OR, 1.43). Ventricular fibrillation (OR, 7.7) and ventricular tachycardia (OR, 2.78) were predictors of in-hospital mortality. Receiving treatment reduced the odds of death and age, sex, and diabetes were risk factors associated with in-hospital mortality after MI.
Conclusions
Age, sex, right bundle branch block arrhythmia, atrial fibrillation, ventricular tachycardia, left bundle branch block arrhythmia, ventricular fibrillation, dyspnea, diabetes, and ST-elevation MI were associated with increased ORs for mortality after MI. Thus, patients with these factors require special attention during hospitalization.
Modeling of Changes in Creatine Kinase after HMG-CoA Reductase Inhibitor Prescription
Hun-Sung Kim, Jiyoung Min, Jiwon Shinn, Oak-Kee Hong, Jang-Won Son, Seong-Su Lee, Sung-Rae Kim, Soon Jib Yoo
Cardiovasc Prev Pharmacother. 2021;3(4):115-123.   Published online October 31, 2021
DOI: https://doi.org/10.36011/cpp.2021.3.e15
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Abstract PDF
Background
Statin-associated muscle symptoms are one of the side effects that physicians should consider when prescribing statins. In this study, creatine kinase (CK) levels were measured following statin prescription, and various factors affecting the CK levels were determined using machine learning.
Methods
Changes in the CK were observed every 3 months for a 12-month period in patients who received statins for the first time at Seoul St. Mary's Hospital. For each visit, we developed four basic models based on changes in the CK levels. Extreme gradient boosting, a scalable end-to-end tree boosting algorithm, which employs a decision-tree-based ensemble machine learning algorithm, was used for the prediction of changes in the CK.
Results
A total of 23,860 patients were included. Among them, 19 patients (0.08%) had increased CK levels of 2,000 IU·L−1 or more 3 months after statin prescription, and 65 patients (0.27%) exhibited CK levels of over 2,000 IU·L−1 at least once during the 12-month study period. The area under the receiver operator characteristic of each model for each visit was 0.709–0.769, and the accuracy was 0.700–0.803. In each of the models, the variables that had the strongest influence on changes in the CK were sex and previous CK value.
Conclusions
Through machine learning, factors influencing changes in the CK were identified. These results will provide the basis for future research, through which the optimal parameters of the CK prediction model can be found and the model can be used in clinical applications.
Development of a Predictive Model for Glycated Hemoglobin Values and Analysis of the Factors Affecting It
HyeongKyu Park, Da Young Lee, So young Park, Jiyoung Min, Jiwon Shinn, Dae Ho Lee, Soon Hyo Kwon, Hun-Sung Kim, Nan Hee Kim
Cardiovasc Prev Pharmacother. 2021;3(4):106-114.   Published online October 31, 2021
DOI: https://doi.org/10.36011/cpp.2021.3.e14
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Abstract PDF
Background
Glycated hemoglobin (HbA1c), which reflects the patient's blood sugar level, can only be measured in a hospital setting. Therefore, we developed a model predicting HbA1c using personal information and self-monitoring of blood glucose (SMBG) data solely obtained by a patient.
Methods
Leave-one-out cross-validation (LOOCV) was performed at two university hospitals. After measuring the baseline HbA1c level before SMBG (Pre_HbA1c), the SMBG was recorded over a 3-month period. Based on these data, an HbA1c prediction model was developed, and the actual HbA1c value was measured after 3 months. The HbA1c values of the prediction model and actual HbA1c values were compared. Personal information was used in addition to SMBG data to develop the HbA1c predictive model.
Results
Thirty model training sessions and evaluations were conducted using LOOCV. The average mean absolute error of the 30 models was 0.659 (range, 0.005–2.654). Pre_HbA1c had the greatest influence on HbA1c prediction after 3 months, followed by post-breakfast blood glucose level, oral hypoglycemic agent use, fasting glucose level, height, and weight, while insulin use had a limited effect on HbA1c values.
Conclusions
The patient's SMBG data and personal information strongly influenced the HbA1c predictive model. In the future, it will be necessary to develop sophisticated predictive models using large samples for stable SMBG in patients.

CPP : Cardiovascular Prevention and Pharmacotherapy