Cardiovascular Prevention and Pharmacotherapy

Original Article

Correlation between metformin intake and prostate cancer: Raeun Kim, Minsun Song, Jiwon Shinn, Hun-Sung Kim; Cardiovasc Prev Pharmacother. 2023;5(3):91-97. Published online July 31, 2023; DOI: https://doi.org/10.36011/cpp.2023.5.e12

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Abstract PDF: Background
The relationship between metformin intake and prostate cancer incidence remains unclear. Therefore, we examined the correlation between prostate cancer and metformin use.
Methods
The subjects were diabetes patients aged ≥50 years who had been diagnosed with prostate cancer and had undergone surgery at Seoul St. Mary's Hospital. Groups taking metformin (MET(+) group) and not taking metformin (MET(–) group) were divided and compared.
Results
The mean preoperative prostate-specific antigen (PSA) levels in the MET(–) and MET(+) groups were 10.7±11.9 and 8.0±5.6 ng/mL, respectively, with no statistically significant difference between the two groups (P=0.387). The average prostate volume of the MET(–) group was 82.4±98.0 mL, and the average prostate volume of the MET(+) group was 55.4±20.1 mL, but there was no statistically significant difference between the two groups (P=0.226). The mean PSA velocity also did not show a significant difference between the two groups (0.025±0.102 ng/mL vs. 0.005±0.012 ng/mL, P=0.221).
Conclusions
We did not identify a significant positive correlation between metformin and prostate cancer. However, preoperational PSA and PSA velocity tended to be lower in the MET(+) group. A sophisticated prospective study with a large sample size should be planned.

Review Article

Diabetes mellitus and cancer: Jae Won Hong; Cardiovasc Prev Pharmacother. 2023;5(3):69-73. Published online July 27, 2023; DOI: https://doi.org/10.36011/cpp.2023.5.e9

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Abstract PDF: Diabetes mellitus and cancer are the most common life-threatening illnesses worldwide. Previous epidemiological studies have suggested a strong association between diabetes mellitus and an increased risk of cancer. Potential biological mechanisms underlying this relationship include obesity, hyperglycemia, hyperinsulinemia, chronic inflammation, and oxidative stress. The most common diabetes-related cancers are pancreatic, hepatocellular, breast, endometrial, and colorectal cancer. Special attention should be paid to patients with diabetes through careful cancer screening and preventive anticancer strategies.

Original Articles

Obesity and 30-day case fatality after hyperglycemic crisis hospitalizations in Korea: a national cohort study: Hojun Yoon, Hyun Ho Choi, Giwoong Choi, Sun Ok Song, Kyoung Hwa Ha, Dae Jung Kim; Cardiovasc Prev Pharmacother. 2023;5(3):74-80. Published online July 27, 2023; DOI: https://doi.org/10.36011/cpp.2023.5.e10

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Abstract PDF Supplementary Material: Background
We determined the case fatality rate associated with hospitalization due to hyperglycemic crises and investigated the relationship between obesity status and case fatality for hyperglycemic crises.
Methods
From the Korean National Health Insurance Service-National Sample Cohort, 729 adults who visited the emergency room or were hospitalized due to hyperglycemic crises between January 1, 2010, and December 31, 2019, were included. Preobesity or obesity was defined as a body mass index ≥23.0 kg/m2. Case fatality rates are presented as the proportion of adults who died within 30 days of hospitalization. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for 30-day fatalities according to preobesity or obesity status.
Results
The 30-day case fatality rate for hyperglycemic crises was 11.2%. In those aged ≥65 years, the fatality rate was twice as high as that in those aged 20 to 64 years (13.8% vs. 6.8%). Adults with preobesity or obesity had a lower fatality rate than those with normal weight (9.5% vs. 14.0%). After adjustment for confounding variables, preobesity or obesity was found to be significantly associated with a decreased risk for 30-day case fatality compared to normal weight (HR, 0.63; 95% CI, 0.40–0.98).
Conclusions
In Korea, hyperglycemic crises had a high fatality rate. Management needs to be improved to prevent hyperglycemic crises and reduce mortality.

Correlation analysis of cancer incidence after pravastatin treatment: Jin Yu, Raeun Kim, Jiwon Shinn, Man Young Park, Hun-Sung Kim; Cardiovasc Prev Pharmacother. 2023;5(2):61-68. Published online April 28, 2023; DOI: https://doi.org/10.36011/cpp.2023.5.e6

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Abstract PDF: Background
Few studies have investigated the cancer-preventive effects of statins, which are known to protect against cardio-cerebrovascular diseases. In this study, we analyzed the degree to which pravastatin, a low-potency statin, could prevent cancer.
Methods
This retrospective cohort study used data from the Korean National Health Insurance Service database. Patients diagnosed with diabetes after the age of 50 years were divided into a pravastatin group and a control group that did not receive any statin prescriptions.
Results
This study included 557 patients in the pravastatin group and 2,221 patients in the control (no statin) group. During the 5-year follow-up, the incidence of cancer was 16.7% (93 of 557 patients) in the pravastatin group and 19.9% (442 of 2,221 patients) in the control group. The incidence of cancer was 22% higher in the control group than in the pravastatin group (hazard ratio, 1.22; 95% confidence interval, 0.97–1.52; P=0.09). Death from various causes occurred at a 45% higher frequency in the control group than in the pravastatin group (hazard ratio, 1.45; 95% confidence interval, 0.99–2.12; P=0.06). However, neither of those relationships reached statistical significance.
Conclusions
Although pravastatin use did not show a significant causal relationship with cancer incidence, fewer cases of cancer occurred in pravastatin users than in controls. However, further large-scale studies are required to confirm these findings.

Review Article

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.

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 Article

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 Articles

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.

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 PDF Supplementary 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.

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.

Review Article

Diabetes in People with Disabilities: a Call for Action: Inha Jung, Eun-Jung Rhee, Won-Young Lee; Cardiovasc Prev Pharmacother. 2021;3(4):82-85. Published online October 31, 2021; DOI: https://doi.org/10.36011/cpp.2021.3.e13

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Abstract PDF: Previous researchers have suggested that people with disabilities have a higher prevalence and risk of type 2 diabetes mellitus than the general population. As diabetes is a well-known risk factor for cardiovascular disease (CVD), developing strategies to prevent and delay its occurrence in people with disabilities is important to reduce the burden of CVD. However, people with disabilities are often excluded from studies and have received little attention from public health authorities and researchers. These unmet needs for health care and being left out of research may affect the progression of diabetes in people with disabilities. Herein, we would like to briefly discuss the increased risk of diabetes and related conditions in people with disabilities and suggest that more attention should be given to this population.

Special Articles

Inflammation in Metabolic Diseases and Insulin Resistance: Won-Young Lee; Cardiovasc Prev Pharmacother. 2021;3(2):31-37. Published online April 30, 2021; DOI: https://doi.org/10.36011/cpp.2021.3.e5

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1 Citations

Abstract PDF

Increased inflammation and insulin resistance are commonly observed in obesity and diabetes. Inflammatory mediators secreted by the adipose tissue contribute to the pathogenesis of diabetes and cardiovascular diseases. Free fatty acids and pro-inflammatory cytokines from adipose tissue inhibit the intracellular insulin signaling pathway, further contributing to the progression of diabetes. Meta-analysis studies show that high sensitivity C-reactive protein can be used as a predictor of future all-cause mortality, including cardiovascular and cancer mortality. In addition to the discovery of novel therapeutic methods targeting inflammatory mediators, basic lifestyle interventions, such as regular exercise, healthy eating, and proper weight control, are absolutely crucial for reducing inflammation and preventing mortality.

Citations

Citations to this article as recorded by

Links between oral microbiome and insulin resistance: Involvement of MAP kinase signaling pathway
Yi-Ru Chang, Wen-Chi Cheng, Ya-Chun Hsiao, Guan-Wei Su, Shan-Jen Lin, Yu-Shan Wei, Hsiu-Chuan Chou, Hsiu-Ping Lin, Guan-Yu Lin, Hong-Lin Chan
Biochimie.2023; 214: 134. CrossRef

Diabetes and Heart Failure: Eun-Jung Rhee; Cardiovasc Prev Pharmacother. 2021;3(2):21-30. Published online April 30, 2021; DOI: https://doi.org/10.36011/cpp.2021.3.e4

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Abstract PDF: Heart failure (HF) in patients with diabetes mellitus has long been considered a consequence of coronary artery disease (CAD). However, recent epidemiological evidence on patients with diabetes showed a significantly increased prevalence of HF in patients with no significant stenosis in the coronary artery. As such, these are thought to be separate entities of diabetic complications. Therefore, HF in patients with diabetes is now considered an independent disease entity of the ‘diabetic heart.’ The mechanism of ‘diabetic heart’ could be due to CAD and diabetic cardiomyopathy caused by altered energy metabolism in the myocardium and advanced glycation end-product accumulation, altered calcium handling, and oxidative stress in the myocardium. Recent cardiovascular outcome trials of anti-diabetic medications have shown the protective effects of certain drugs against HF in patients with and without diabetes. In this review, the relationship between diabetes and the treatment and prevention of HF is summarized.

Review Articles

Prevention of Type 2 Diabetes: Jong Dai Kim, Won-Young Lee; Cardiovasc Prev Pharmacother. 2020;2(3):63-76. Published online July 31, 2020; DOI: https://doi.org/10.36011/cpp.2020.2.e10

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Abstract PDF: The number of patients with type 2 diabetes (T2D) is increasing worldwide and that in Korea, particularly, has shown an exponential increase with a rise in the older population. The diabetic population is predicted to soar up to 6 million by 2050. The prevalence of diabetes among Korean adults is approximately 15%, while that of prediabetes is 25%, with a total prevalence of 40%. As 40% of the prediabetes cases subsequently progress to T2D, prevention through proactive interventions at the prediabetes stage is essential to reduce the socioeconomic burden due to T2D and the complications of diabetes. With regard to the prevention of T2D, new findings have been published related to the implementation of lifestyle interventions such as exercise and diet as well as drug treatments and surgeries, which have deepened our understanding of the prevention of T2D. Based on published evidence, this review aimed to examine the methods used in the prevention of diabetes.

Paradigm Shift for the Treatment of Type 2 Diabetes Mellitus in Patients with Cardiovascular Disease: Cardiologist's Perspective: Doo Soo Jeon; Cardiovasc Prev Pharmacother. 2020;2(1):11-17. Published online January 31, 2020; DOI: https://doi.org/10.36011/cpp.2020.2.e4

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Abstract PDF: Type 2 diabetes mellitus (T2DM) is a complex disorder and is associated with an increased risk for developing atherosclerotic cardiovascular disease. Control of major risk factors of T2DM can reduce major adverse cardiovascular events (MACEs) in patients. Glycemic control has long been the gold standard for treatment of T2DM. However, strict blood glucose control strategies have repeatedly failed in the prevention of cardiovascular events in key clinical trials. The 2019 American and European practice guidelines for the prevention of cardiovascular disease in patients with T2DM have recommended the use of novel hypoglycemic agents, such as sodium glucose transporter 2 inhibitors and glucagonlike peptide-1 receptor antagonist, which have shown significant reductions in the risk of MACE in spite of their modest glycemic control capacity. A paradigm shift from the glucosecentered approach in treating diabetic patients with cardiovascular disease is imperative. Based on positive outcomes from previous evidence, the reduction of the risk of MACE should be a primary objective for treatment.

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