Cardiovascular Prevention and Pharmacotherapy

Review Articles

The prognostic role of lipoprotein(a) in cardiovascular disease: Eun-Jung Rhee; Received January 7, 2025 Accepted January 14, 2025 Published online January 22, 2025; DOI: https://doi.org/10.36011/cpp.2025.7.e3 [Epub ahead of print]

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Abstract PDF: Lipoprotein(a) (Lp(a)), is not a new entity; however, it has become an increasingly discussed and studied risk factor for atherosclerotic cardiovascular disease (CVD) and aortic valve stenosis. Recent guidelines recommend measuring Lp(a) levels throughout the lifetime in patients at high risk for CVD, as Lp(a) can serve as a signature marker for identifying individuals at elevated risk for CVD. Numerous genetic and epidemiological studies have underscored the significant causal role of Lp(a) in the incidence of CVD. Individuals with high Lp(a) levels face an increased risk for CVD, even with optimal low-density lipoprotein cholesterol lowering. Furthermore, Lp(a) levels are primarily determined by genetics and are not significantly reduced by lifestyle changes or certain medications. This review will discuss the characteristics, genetic factors, and epidemiological properties of Lp(a) in relation to CVD.

Nonalcoholic fatty liver disease and heart failure with preserved ejection fraction: a focus on risk factors and management: Joonpyo Lee, Mi-Seung Shin; Received January 1, 2025 Accepted January 13, 2025 Published online January 21, 2025; DOI: https://doi.org/10.36011/cpp.2025.7.e2 [Epub ahead of print]

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Abstract PDF: Nonalcoholic fatty liver disease (NAFLD) and heart failure with preserved ejection fraction (HFpEF) are two increasingly prevalent conditions that share common risk factors, including obesity, diabetes, and aging. NAFLD, marked by hepatic steatosis, is a leading cause of liver disease globally, with cardiovascular disease accounting for most deaths among those affected. HFpEF, characterized by diastolic dysfunction and systemic inflammation, accounts for a growing share of heart failure cases, especially among older adults. The bidirectional relationship between NAFLD and HFpEF involves shared mechanisms such as systemic inflammation, insulin resistance, and metabolic dysfunction. These overlapping processes create a vicious cycle that exacerbates each condition. This review emphasizes the shared pathophysiology, risk factors, and management strategies for these interconnected diseases. Promising interventions, including exercise, weight loss, and emerging pharmacological treatments like sodium-glucose cotransporter 2 inhibitors, are effective in addressing both NAFLD and HFpEF. By targeting these common pathways, there is a unique opportunity to develop integrated treatment approaches that could improve outcomes for affected patients.

Pharmacological management of diabetes in older adults: Junghyun Noh; Received January 9, 2025 Accepted January 15, 2025 Published online January 20, 2025; DOI: https://doi.org/10.36011/cpp.2025.7.e1 [Epub ahead of print]

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Abstract PDF: As the global population continues to age, the rising prevalence of diabetes among older adults has become a significant public health concern. Consequently, effective and safe management of diabetes mellitus in this population is an increasingly critical focus in clinical practice. Older patients present considerable variability in functional status, with many experiencing physical disabilities, visual impairments, cognitive decline, or psychological conditions such as depression. Therefore, individualized treatment strategies that consider the presence and progression of geriatric syndromes, comorbidities, and the risk of hypoglycemia are essential for optimizing the pharmacological management of diabetes in older adults.

Relationship between autonomic and peripheral neuropathies and cardiovascular outcomes in diabetes: Jae-Seung Yun; Cardiovasc Prev Pharmacother. 2024;6(4):123-127. Published online October 31, 2024; DOI: https://doi.org/10.36011/cpp.2024.6.e17

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Abstract PDF: This review explores the complex relationship between diabetic neuropathy and cardiovascular disease (CVD). Neuropathy, a common complication of type 1 and type 2 diabetes, is divided into autonomic and peripheral types, each impacting cardiovascular health. Cardiovascular autonomic neuropathy, a form of autonomic neuropathy, is associated with various CVD complications, including arrhythmias, impaired nocturnal blood pressure regulation, and increased mortality. The prevalence of cardiovascular autonomic neuropathy varies depending on the type and duration of diabetes and is influenced by factors like glycemic control and metabolic stress. Peripheral polyneuropathy, which is often linked to diabetic foot disease, is also correlated with elevated CVD risk; research suggests shared pathophysiological mechanisms between peripheral neuropathy and cardiovascular conditions. Screening for neuropathies using tools like the Michigan Neuropathy Screening Instrument and heart rate variability analyses can facilitate early detection of CVD risk. Additionally, emerging technologies, like deep learning models, have demonstrated promise in detecting early cardiovascular patterns associated with autonomic neuropathy through electrocardiogram analysis. These findings underscore the value of integrating novel diagnostic approaches for early intervention. As CVD represents a leading cause of death among patients with diabetes, this article emphasizes the need for thorough assessment and proactive management of neuropathy to mitigate cardiovascular risk. The review recommends a multidisciplinary approach to diabetes care, including early screening, accurate risk stratification, and targeted therapeutic strategies to prevent or slow the progression of CVD in patients with autonomic and peripheral neuropathies. Further research is warranted to clarify the optimal intervention strategies for reducing CVD risk in these populations.

Sodium-glucose cotransporter 2 inhibitors in cardiocerebrovascular disease: Jin Joo Park; Cardiovasc Prev Pharmacother. 2024;6(4):103-108. Published online October 31, 2024; DOI: https://doi.org/10.36011/cpp.2024.6.e16

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Abstract PDF: Cardiovascular disease is a leading cause of global mortality, necessitating effective strategies for prevention and treatment. The cardiovascular disease continuum concept highlights the progression from risk factors such as hypertension and diabetes mellitus to advanced stages, including heart failure (HF) and death. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, initially developed to manage diabetes, have emerged as effective therapies across all stages of the cardiovascular disease continuum. Numerous cardiovascular outcome trials demonstrate that SGLT2 inhibitors significantly reduce major adverse cardiovascular events and hospitalizations for HF in patients with and without established atherosclerotic cardiovascular disease. Notably, SGLT2 inhibitors have shown remarkable benefits in reducing HF risk, even in patients without diabetes, including those with HF and preserved ejection fraction. Furthermore, recent studies in post–myocardial infarction patients suggest potential benefits in reducing hospitalizations for HF. Despite their widespread use, the precise mechanisms by which SGLT2 inhibitors confer cardiovascular protection remain unclear, suggesting the need for further investigation. In conclusion, SGLT2 inhibitors have revolutionized cardiovascular disease management, offering significant therapeutic potential across a broad spectrum of patients, and are expected to play an increasingly prominent role in both the prevention and treatment of cardiovascular disease.

Paradigm shift from glucocentric to organ protection for the management of hyperglycemia in patients with type 2 diabetes: Jie-Eun Lee, Jong Chul Won; Cardiovasc Prev Pharmacother. 2024;6(4):116-122. Published online October 31, 2024; DOI: https://doi.org/10.36011/cpp.2024.6.e15

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Abstract PDF: The UK Prospective Diabetes Study was the first study to investigate the effectiveness of glycemic control in patients with type 2 diabetes. Since then, many studies have evaluated the impact of intensive glycemic control on diabetes-related morbidities and mortality. The results of these studies were intended to change the paradigm for controlling glycated hemoglobin and preventing diabetes-related complications, but the beneficial outcomes were limited to microvascular diseases rather than diabetes-related cardiorenal diseases and deaths. This has emphasized the need for comprehensive management of other risk factors (hypertension, dyslipidemia, renal failure, etc.) in addition to hyperglycemia to prevent atherosclerotic cardiovascular diseases and end-stage renal disease in type 2 diabetes. Since 2008, clinical trials to demonstrate cardiovascular safety have shown a beneficial effect of sodium-glucose transporter 2 inhibitors or glucagon-like peptide-1 receptor agonists on macrovascular or renal complications in patients with type 2 diabetes. Recently, major societies around the world including the Korean Diabetes Association, have shifted the goals of diabetes management from the typical glucocentric view to cardiorenal outcome-oriented (organ protection) care, which has been widely accepted and is gradually applied to primary care.

Moyamoya disease: insights into the clinical implications of the RNF213 gene: Taedong Ok; Cardiovasc Prev Pharmacother. 2024;6(4):109-115. Published online October 31, 2024; DOI: https://doi.org/10.36011/cpp.2024.6.e14

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Abstract PDF: Moyamoya disease (MMD) is a rare cerebrovascular disorder characterized by progressive stenosis of the terminal internal carotid arteries and the formation of compensatory collateral vessels, which appear as a “puff of smoke” on cerebral angiography. It is a significant cause of stroke in East Asia, with an incidence of 0.5 to 1.5 cases per 100,000 people annually. The etiology of MMD remains unclear; however, the identification of the RNF213 gene, particularly the R4810K variant, as a major susceptibility factor among the East Asian population, has provided crucial insights into the disease's pathophysiology and clinical manifestations. MMD typically presents with transient ischemic attacks, ischemic and hemorrhagic strokes, seizures, headaches, and cognitive deficits. Diagnostic criteria have evolved to emphasize advanced imaging techniques. Pathological features include fibrocellular intimal thickening, irregular undulation of the elastic lamina, and the formation of moyamoya vessels. The mutation in the RNF213 gene impairs the degradation of proteins involved in vessel development, leading to abnormal angiogenesis. Genotype-phenotype studies indicate that the RNF213 variant is associated with an earlier onset, transient ischemic attacks, infarctions, and involvement of the posterior cerebral artery, although its effects vary between regions. Additionally, the homozygous RNF213 variant consistently correlates with an earlier age of onset and a higher risk of cerebral infarction. However, further research is necessary to fully understand its long-term impacts and its relationship with revascularization outcomes. Ongoing research is crucial to fully comprehend the pathophysiology and genetics of MMD, improve prognostic predictions, and develop novel therapies.

Use of dual-energy x-ray absorptiometry for body composition in chronic disease management: Tae Nyun Kim; Cardiovasc Prev Pharmacother. 2024;6(4):128-134. Published online October 31, 2024; DOI: https://doi.org/10.36011/cpp.2024.6.e13

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Abstract PDF: As individuals age or contend with chronic diseases, shifts in body composition often emerge, characterized by a loss of muscle mass and an increase in fat mass, even among those with stable body weight. Both obesity and sarcopenia are key drivers of frailty, disability, and heightened morbidity and mortality. The simultaneous decline in skeletal muscle and accumulation of visceral fat can work synergistically, magnifying their detrimental effects on physical function and metabolic health. Today, dual-energy x-ray absorptiometry (DEXA) is widely recognized as one of the most versatile imaging techniques for assessing not only osteoporosis but also sarcopenia and obesity. Whole-body DEXA facilitates comprehensive analysis, offering detailed insights into fat mass, non-bone lean mass, and bone mineral content at both total and regional levels. DEXA is highly valued for its accuracy, reproducibility, speed, affordability, and low radiation exposure. Furthermore, advancements in DEXA technology and software now allow for precise estimation of visceral adipose tissue. This review underscores the clinical applications of whole-body DEXA, focusing on the use of muscle and fat mass indices in diagnosing low muscle mass, sarcopenia, and sarcopenic obesity, aligned with the latest research and guidelines.

Original Article

Health behaviors, knowledge, and attitudes toward cardiovascular disease risk factors in young Iraqi adults: a sample from Erbil, Iraq: Halmat Ahmed Sulaiman, Isil Isik Andsoy; Cardiovasc Prev Pharmacother. 2024;6(3):92-101. Published online July 30, 2024; DOI: https://doi.org/10.36011/cpp.2024.6.e12

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Abstract PDF: Background
Cardiovascular disease continues to be a leading cause of death among young people globally. This cross-sectional study was designed to assess the health behaviors, knowledge, and attitudes regarding cardiovascular disease risk factors among young adults in Erbil, Iraq.
Methods
Data were collected using the WHO STEPS Instrument for Chronic Disease Risk Factor Surveillance and the Heart Disease Fact Questions.
Results
Ninety percent of participants demonstrated moderate to high knowledge and exhibited a positive attitude. Multiple linear regression analysis revealed that while a history of smoking, a lack of knowledge, and the absence of formal education negatively impacted knowledge levels, being aged 38 to 45 years, recognizing the importance of consuming less salt, walking for at least 10 minutes on 5 or more days per week, and regularly checking blood sugar levels positively contributed to knowledge. Unwillingness to change lifestyle had the most significant negative influence on knowledge.
Conclusions
Establishing effective educational interventions may increase knowledge and promote more positive attitudes.

Review Article

Re-evaluating the PCSK9 guidelines for low-density lipoprotein cholesterol targets: weighing the benefits against the risks: Terry Gbaa, John Bolodeoku; Cardiovasc Prev Pharmacother. 2024;6(3):85-91. Published online July 30, 2024; DOI: https://doi.org/10.36011/cpp.2024.6.e11

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Abstract PDF: Cardiovascular disease management has made significant progress with lipid-lowering interventions, primarily statin therapy. However, statins' side effects, combined with their variable efficacy, have sparked interest in alternative treatments, particularly proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies. These biologics, approved by the US Food and Drug Administration and the European Medicines Agency, have shown a significant impact on lipid levels, particularly low-density lipoprotein cholesterol (LDL-C), resulting in a 50% to 60% reduction. Despite the benefits of PCSK9 inhibitors, the guidelines for their use differ, with specific thresholds determining eligibility. The National Institute for Health and Care Excellence recommends starting PCSK9 therapy for patients with LDL-C levels above 3.5 mmol/L and lipid levels above 5.0 mmol/L who do not have cardiovascular disease. This rigid framework, while cost-effective, may exclude a subset of patients who do not meet these criteria despite having a high cardiovascular risk. The limited scope of these guidelines presents a challenge for specialists managing patients excluded as a result of LDL-C levels that fall just below the threshold but still show signs of significant cardiovascular risk. Recent audits revealed that a significant proportion of patients fall into this grey area, emphasizing the importance of re-evaluating LDL targets for PCSK9 inhibitor initiation. Biological variations, pharmacogenomics, and other factors all contribute to this challenge, highlighting the importance of personalized medicine.

Original Article

Cardiovascular risk assessment of newborns in Nigeria using the atherogenic index of plasma and its associations with gestational age and birth weight: a cross-sectional hospital-based study: Obinna Victory Obaji, Uche Charles Adizua, Ndubuisi Kennedy Chukwudi, Daberechi Kenneth Adiele, Justus Uchenna Onu; Cardiovasc Prev Pharmacother. 2024;6(2):65-73. Published online April 26, 2024; DOI: https://doi.org/10.36011/cpp.2024.6.e9

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Abstract PDF: Background
The prevalence of atherosclerotic cardiovascular disease is rising, and its onset from childhood is widely studied. Prematurity and low birth weight were associated with higher atherogenic risk when assessed using some lipid ratios. However, the atherogenic index of plasma (AIP), a sensitive marker for atherosclerosis is understudied in newborns. Utilizing AIP, this study aimed to determine atherogenic risk prevalence among newborns and its association with gestational age and birth weight.
Methods
Newborns were consecutively recruited, and their lipid profiles were determined. The AIP was calculated as the logarithm to base 10 (log10) of the ratio of molar concentrations of triglyceride to high-density lipoprotein cholesterol. The atherogenic risk was operationalized using AIP: high, >0.24; medium, 0.1–0.24; and low/no risk, <0.1. The relationship between AIP values, gestational age, and birth weight was analyzed using Pearson correlation.
Results
The mean AIP of the 167 newborns studied was –0.35±0.34, which is within the global reference range. Three (1.8%), 10 (6.0%), and 154 (92.2%) newborns were in the high, medium, and low/no atherogenic risk categories, respectively. Hence, 13 newborns (7.8%) had medium to high atherogenic risk. AIP had a moderate significantly positive relationship only with gestational age (r=0.35, P<0.001).
Conclusions
The study found an atherogenic risk prevalence of 7.8% using AIP in newborns which, contrary to previous studies that used other ratios, has no significant association with birth weight, correlating positively with gestational age, though is lowest in late preterms. Follow-up studies will elucidate these findings.

Review Articles

Expectations and concerns regarding medical advertisements via large commercial medical platform advertising companies: a legal perspective: Raeun Kim, Hakyoung Park, Jiwon Shinn, Hun-Sung Kim; Cardiovasc Prev Pharmacother. 2024;6(2):48-56. Published online April 26, 2024; DOI: https://doi.org/10.36011/cpp.2024.6.e8

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Abstract PDF: Advertising in the medical and legal fields, which are among Korea's leading professions, has increasingly utilized major advertising platforms such as LawTalk and UNNI—two of the most prominent and contentious platforms in their respective fields. While it is generally unproblematic for professionals like lawyers and doctors to promote public interest through advertising on these commercial platforms, the creation of a profit-driven structure has the potential to undermine their professional ecosystems. This article explores the issues associated with advertising in the medical field through large commercial platforms, drawing on notable examples from the legal and medical fields in Korea. Specifically, we analyze two of the most popular yet controversial platforms in these sectors, LawTalk and UNNI. In Korea, the format and method of advertising are legal as long as they do not involve referring or soliciting clients, thereby making platform advertising lawful when used solely for that purpose. Nevertheless, it is crucial to prevent medical advertising platforms from establishing market monopolies by skirting various profit regulations and laws. In response to these concerns, the Korean Bar Association has prohibited all advertisements by platform companies. The medical community should closely examine the rationale and process behind this decision. Given the significant social influence of large corporate platforms and the unique social responsibilities of the medical and legal professions, future platform advertising should be subject to distinct legal and institutional regulations that differ from those applied to general services.

The emergence and clinical significance of artificial intelligence–enhanced electrocardiography: Yong-Soo Baek; Cardiovasc Prev Pharmacother. 2024;6(2):41-47. Published online April 26, 2024; DOI: https://doi.org/10.36011/cpp.2024.6.e7

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1 Citations

Abstract PDF

The integration of artificial intelligence (AI) with electrocardiography (ECG), a technology known as AI-ECG, represents a transformative leap in the field of cardiovascular medicine. This innovative approach has significantly advanced the capabilities of ECG, traditionally used for diagnosing heart diseases. AI-ECG excels in detecting subtle changes and interconnected patterns in cardiac waveforms, offering a level of precision and sensitivity that was previously unattainable with conventional methods. The scope of AI-ECG extends beyond the realm of heart diseases. It has shown remarkable potential in predicting and identifying the impacts of noncardiac conditions on heart health, thereby broadening the diagnostic capabilities of ECG. This is especially valuable given the complex nature of cardiovascular diseases and their interactions with other health conditions. Despite its groundbreaking potential, AI-ECG faces several challenges. One of the primary concerns is the "black box" nature of AI algorithms, which can make the decision-making process opaque and difficult to interpret. This poses a challenge in medical settings where understanding the rationale behind a diagnosis is crucial. Additionally, the effectiveness of AI-ECG is dependent on the quality and diversity of the datasets used to train the algorithms. Limited or biased datasets can lead to inaccuracies and diminish the reliability of the technology. However, the benefits of AI-ECG are significant. It enables faster, more accurate diagnoses and has the potential to greatly enhance the efficiency of cardiovascular care. As research and technology continue to evolve, AI-ECG is poised to become an indispensable tool in the diagnosis and management of heart diseases.

Citations

Citations to this article as recorded by

AI-Enhanced ECG Applications in Cardiology: Comprehensive Insights from the Current Literature with a Focus on COVID-19 and Multiple Cardiovascular Conditions
Luiza Camelia Nechita, Aurel Nechita, Andreea Elena Voipan, Daniel Voipan, Mihaela Debita, Ana Fulga, Iuliu Fulga, Carmina Liana Musat
Diagnostics.2024; 14(17): 1839. CrossRef

Original Articles

Cardiac rehabilitation using intensive lifestyle habituation combined with outdoor exercise in an urban forest environment for primary and secondary prevention of coronary artery disease: a feasibility test: Jong-Young Lee, Kee-Chan Joo, Kyung-Su Choi, Dae-Sik Yoon; Cardiovasc Prev Pharmacother. 2024;6(2):74-83. Published online April 25, 2024; DOI: https://doi.org/10.36011/cpp.2024.6.e10

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Abstract PDF: Background
We aimed to examine the feasibility of intensive lifestyle habituation with a subsequent home program, including forest-based exercise, as an alternative approach to conventional cardiac rehabilitation for both primary and secondary prevention of coronary artery disease (CAD).
Methods
A total of 28 participants were included in a 1-week intensive education program aimed at fostering desirable lifestyle habits in the study: 17 patients who underwent percutaneous coronary intervention and 11 participants at high risk of CAD. Subsequently, they engaged in a self-directed, home-based program that included unstructured exercise in an urban forest. The terrain of the urban forest was analyzed to estimate metabolic equivalent levels and to assess safety and accessibility for patient exercise.
Results
Throughout the program, no adverse cardiac events were reported. Additionally, risk factors for CAD—including body composition, blood sugar levels, hemodynamic variables, total cholesterol levels, and cardiorespiratory endurance—showed significant improvement in both groups.
Conclusions
Intensive lifestyle habituation and unstructured, self-directed exercise in the forest were as effective and safe as conventional cardiac rehabilitation for patients with CAD. The study demonstrated that an urban forest could serve as a safe exercise environment in both primary and secondary prevention strategies for CAD.

Changes in cardiovascular-related health behaviors after the end of social distancing: the 2023 Cardiovascular Disease Prevention Awareness Survey: Jaeyong Lee, Eunji Kim, Won-Young Lee, Eun-Jung Rhee, Hyeon Chang Kim; Cardiovasc Prev Pharmacother. 2024;6(2):57-64. Published online April 5, 2024; DOI: https://doi.org/10.36011/cpp.2024.6.e6

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Abstract PDF Supplementary Material: Background
The COVID-19 pandemic and the implementation of social distancing have been reported to negatively impact cardiovascular-related health behaviors. However, the effects of lifting social distancing restrictions on these health behaviors remain unclear. This study investigated public awareness and behavioral changes related to cardiovascular disease prevention after the end of social distancing.
Methods
Between June 5 and June 12, 2023, 2,000 adults participated in the 2023 Cardiovascular Disease Prevention Awareness Survey in Korea. The survey comprehensively addressed sociodemographic factors, cardiometabolic disease history, cardiovascular disease concern, prevention awareness, and behavioral changes after the end of social distancing. Logistic regression analyses were performed to assess the associations between behavioral changes and sociodemographic factors.
Results
Cardiovascular disease ranked as the second most feared disease (most feared, 18.0%; second most feared, 26.3%) after cancer (most feared, 42.3%; second most feared, 21.7%). Among nine cardiovascular disease prevention recommendations, stress management, being physically active, and maintaining a healthy diet were perceived as the most challenging recommendations. After the end of social distancing, there were more positive changes than negative changes in smoking, alcohol consumption, dietary habits, physical activity, and healthcare service use, whereas stress management more frequently changed negatively (40.0%) than it changed positively (19.5%).
Conclusions
Positive changes in cardiovascular-related health behaviors, except for stress management, were observed after the end of social distancing. Further research is necessary to fully comprehend the impact of discontinuing social distancing practices.

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