Metabolic syndrome awareness in the general Korean population: results from a nationwide survey.

BACKGROUND/AIMS: Metabolic syndrome (MetS) raises the risk of cardiovascular disease and type 2 diabetes. An awareness of MetS is vital for early detection and proactive management, which can mitigate the risks associated with MetS. Therefore, our study aimed to investigate the level of awareness of MetS among the Korean population. METHODS: We conducted a nationwide survey between January and February 2023 among a representative sample of the Korean population using an online survey. Information regarding the awareness of MetS and its risk, the importance of lifestyle modification, and health behavior were collected. The question about the awareness of MetS was "How much do you think you know about MetS?" and there were five answers: 1) I know very well, 2) I know well, 3) I know a little, 4) I do not know, and 5) I have no idea. The high-awareness group was defined as those who answered that they knew very well or well. RESULTS: Among 1,000 participants (mean age, 45.7 ± 13.2 yr), 29% were unaware of MetS, and only 20.8% had high awareness. The high-awareness group was significantly more knowledgeable about lifestyle modifications and demonstrated better health behaviors. After adjustment for possible confounding factors, younger age, low household income, and absence of comorbidity were independently associated with a lack of awareness regarding MetS. CONCLUSION: The high-awareness group showed greater knowledge of the importance of lifestyle modifications and better health behaviors regarding MetS. The findings highlight the need for improved public education and awareness programs regarding MetS.

Adiponectin and cardiometabolic trait and mortality: where do we go?

Adiponectin is an adipocyte-derived cytokine known for its cardioprotective effects in preclinical studies. Early epidemiologic studies replicated these findings and drew great interest. Subsequent large-scale prospective cohorts, however, showed that adiponectin levels seemed not to relate to incident coronary artery disease (CAD). Even more surprisingly, a paradoxical increase of all-cause and cardiovascular (CV) mortality with increased adiponectin levels was reported. The adiponectin-mortality paradox has been explained by some groups asserting that adiponectin secretion is promoted by elevated natriuretic peptides (NP). Other groups have proposed that adiponectin is elevated due to adiponectin resistance in subjects with metabolic syndrome or heart failure (HF). However, there is no unifying theory that can clearly explain this paradox. In patients with HF with reduced ejection fraction (HFrEF), stretched cardiomyocytes secrete NPs, which further promote release of adiponectin from adipose tissue, leading to adiponectin resistance. On the other hand, adiponectin biology may differ in patients with heart failure with preserved ejection fraction (HFpEF), which constitutes 50% of all of HF. Most HFpEF patients are obese, which exerts inflammation and myocardial stiffness, i.e. likely to prevent myocardial stretch and subsequent NP release. This segment of the patient population may display different adiponectin biology from its HFrEF counterpart. Dissecting the adiponectin-mortality relationship in terms of different HF subtypes may help to comprehensively understand this paradox. Mendelian randomization (MR) analyses claimed that adiponectin levels are not causally related to CAD or metabolic syndrome. Results from MR studies, however, should be interpreted with great caution because the underlying history of CAD or CHF was not taken into account in these analyses, an issue that may substantially confound the results. Here, we discuss many aspects of adiponectin; cardiometabolic traits, therapeutic interventions, and the ongoing debate about the adiponectin paradox, which were recently described in basic, epidemiologic, and clinical studies.

Cardiovascular effects of omega-3 fatty acids: Hope or hype?

Omega-3 fatty acids have emerged as a new option for controlling the residual risk for cardiovascular disease (CVD) in the statin era after a clinical trial (REDUCE-IT) reported positive results with icosapent ethyl (IPE) in patients receiving maximally tolerated statin therapy. However, another trial which used high dose eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) combination (STRENGTH) has failed. Together, these results raise clinically important questions. Are effects of omega-3 fatty acids neutral or beneficial in patients on statin therapy, or perhaps even harmful? The current contradictory results could be attributed to different types of omega-3 fatty acids (only EPA or combination of EPA + DHA), doses (higher vs. lower dose) of omega-3 fatty acids or different comparators (corn oil or mineral oil), as well as the underlying severity of the CVD risk or use of statins. Together with these issues, we will discuss different biological and clinical effects of various types of omega-3 fatty acids and then interpret different results of past and current clinical studies and propose practical suggestions, which could be applied in patient management.

Association of pericardial adipose tissue with left ventricular structure and function: a region-specific effect?

BACKGROUND: The independent role of pericardial adipose tissue (PAT) as an ectopic fat associated with cardiovascular disease (CVD) remains controversial. This study aimed to determine whether PAT is associated with left ventricular (LV) structure and function independent of other markers of general obesity. METHODS: We studied 2471 participants (50.9 % women) without known CVD from the Korean Genome Epidemiology Study, who underwent 2D-echocardiography with tissue Doppler imaging (TDI) and computed tomography measurement for PAT. RESULTS: Study participants with more PAT were more likely to be men and had higher cardiometabolic indices, including blood pressure, glucose, and cholesterol levels (all P < 0.001). Greater pericardial fat levels across quartiles of PAT were associated with increased LV mass index and left atrial volume index (all P < 0.001) and decreased systolic (P = 0.015) and early diastolic (P < 0.001) TDI velocities, except for LV ejection fraction. These associations remained after a multivariable-adjusted model for traditional CV risk factors and persisted even after additional adjustment for general adiposity measures, such as waist circumference and body mass index. PAT was also the only obesity index independently associated with systolic TDI velocity (P < 0.001). CONCLUSIONS: PAT was associated with subclinical LV structural and functional deterioration, and these associations were independent of and stronger than with general and abdominal obesity measures.

New Trends in Dyslipidemia Treatment.

Dyslipidemia is one of the most important risk factors for cardiovascular (CV) disease. Statin therapy has dramatically improved CV outcomes and is the backbone of current lipid-lowering therapy, but despite well-controlled low-density lipoprotein cholesterol (LDL-C) levels through statin administration, up to 40% patients still experience CV disease. New therapeutic agents to tackle such residual cholesterol risk by lowering not only LDL-C but triglycerides (TG), TG-rich lipoproteins (TRL), or lipoprotein(a) (Lp(a)) are being introduced. Ezetimibe, proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies, PCSK9 small interference RNA (siRNA), and bempedoic acid added to statin therapy have shown additional improvement to CV outcomes. Recent trials administering eicosapentaenoic acid to patients with high TG despite statin therapy have also demonstrated significant CV benefit. Antisense oligonucleotide (ASO) therapies with hepatocyte-specific targeting modifications are now being newly introduced with promising lipid-lowering effects. ASOs targeting TG/TRL, such as angiopoietin-like 3 or 4 (ANGPTL3 or ANGPTL4), apolipoprotein C-III (APOC3), or Lp(a) have effectively lowered the corresponding lipid profiles without requiring high or frequent doses. Clinical outcomes from these novel therapeutics are yet to be proven. Here, we review current and emerging therapeutics targeting LDL-C, TG, TRL, and Lp(a) to reduce the residual CV risk.

Lipoprotein(a) and Cardiovascular Diseases　- Revisited.

Two decades ago, it was recognized that lipoprotein(a) (Lp(a)) concentrations were elevated in patients with cardiovascular disease (CVD). However, the importance of Lp(a) was not strongly established due to a lack of both Lp(a)-lowering therapy and evidence that reducing Lp(a) levels improves CVD risk. Recent advances in clinical and genetic research have revealed the crucial role of Lp(a) in the pathogenesis of CVD. Mendelian randomization studies have shown that Lp(a) concentrations are causal for different CVDs, including coronary artery disease, calcified aortic valve disease, stroke, and heart failure, despite optimal low-density lipoprotein cholesterol (LDL-C) management. Lp(a) consists of apolipoprotein (apo) B100 covalently bound to apoA. Thus, Lp(a) has atherothrombotic traits of both apoB (from LDL) and apoA (thrombo-inflammatory aspects). Although conventional pharmacological therapies, such as statin, niacin, and cholesteryl ester transfer protein, have failed to significantly reduce Lp(a) levels, emerging new therapeutic strategies using proprotein convertase subtilisin-kexin type 9 inhibitors or antisesnse oligonucleotide technology have shown promising results in effectively lowering Lp(a). In this review we discuss the revisited important role of L(a) and strategies to overcome residual risk in the statin era.

Strategies to Overcome Residual Risk During Statins Era.

At present, atherosclerosis is one of the most important field in clinical and research medicine. Because it is closely related to cardiovascular (CV) and endocrine disorders such as coronary artery disease, cardiometabolic disorders, much research on how to manage atherosclerosis has been performed. The low-density lipoprotein cholesterol (LDL-C) concentration has been established as an independent risk factor for developing atherosclerosis, and considerable effort has been committed to educating both physicians and the general public on the importance of lowering LDL-C with statins. Although statins have already significantly improved CV outcomes, patients with LDL-C target levels achieved by intense statin therapy still have significant remaining CV risk. Statins already play a central role in managing hyperlipidemia; however, residual risk with statins is an important field of managing remaining CV risk. Recent studies have suggested residual cholesterol and inflammation risks in causing CV events. In the current review, we will discuss residual risk and suggest strategies to overcome it in the statins era.

Impact of Longitudinal Changes in Metabolic Syndrome Status over 2 Years on 10-Year Incident Diabetes Mellitus.

BACKGROUND: Metabolic syndrome (MetS) is a known predictor of diabetes mellitus (DM), but whether longitudinal changes in MetS status modify the risk for DM remains unclear. We investigated whether changes in MetS status over 2 years modify the 10-year risk of incident DM. METHODS: We analyzed data from 7,317 participants aged 40 to 70 years without DM at baseline, who took part in 2001 to 2011 Korean Genome Epidemiology Study. Subjects were categorized into four groups based on repeated longitudinal assessment of MetS status over 2 years: non-MetS, resolved MetS, incident MetS, and persistent MetS. The hazard ratio (HR) of new-onset DM during 10 years was calculated in each group using Cox models. RESULTS: During the 10-year follow-up, 1,099 participants (15.0%) developed DM. Compared to the non-MetS group, the fully adjusted HRs for new-onset DM were 1.28 (95% confidence interval [CI], 0.92 to 1.79) in the resolved MetS group, 1.75 (95% CI, 1.30 to 2.37) in the incident MetS group, and 1.98 (95% CI, 1.50 to 2.61) in the persistent MetS group (P for trend <0.001). The risk of DM in subjects with resolved MetS was significantly attenuated compared to those with persistent MetS over 2 years. In addition, the adjusted HR for 10-year developing DM gradually increased as the number of MetS components increased 2 years later. CONCLUSION: We found that discrete longitudinal changes pattern in MetS status over 2 years associated with 10-year risk of DM. These findings suggest that monitoring change of MetS status and controlling it in individuals may be important for risk prediction of DM.

Controversies in the 2017 ACC/AHA Hypertension Guidelines: Who Can Be Eligible for Treatments Under the New Guidelines?　- An Asian Perspective.

Until the 2017 ACC/AHA Hypertension Guidelines were released, the target blood pressure (BP) for adults with hypertension (HTN) was 140/90 mmHg in most of the guidelines. The new 2018 ESC/ESH, Canadian, Korean, Japan, and Latin American hypertension guidelines have maintained the <140/90 mmHg for the primary target in the general population and encourage reduction to <130/80 if higher risk. This is more in keeping with the 2018 American Diabetes Association guidelines. However, the 2017 ACC/AHA guidelines classify HTN as BP ≥130/80 mmHg and generally recommend target BP levels below 130/80 mmHg for hypertensive patients independently of comorbid disease or age. Although the new guidelines mean that more people (nearly 50% of adults) will be diagnosed with HTN, the cornerstone of therapy is still lifestyle management unless BP cannot be lowered to this level; thus, more people will require BP-lowering medications. To date, there have been many controversies about the definition of HTN and the target BP. Targeting an intensive systolic BP goal can increase the adverse effects of multiple medications and the cardiovascular disease risk by excessively lowering diastolic BP, especially in patients with high risk, including those with diabetes, chronic kidney disease, heart failure, and coronary artery disease, and the elderly. In this review, we discuss these issues, particularly regarding the optimal target BP.

Inflammatory and metabolic mechanisms underlying the calcific aortic valve disease.

Although calcific aortic stenosis is a very common disease with major adverse cardiovascular events and healthcare costs, there are no effective medical interventions to delay or halt its progression. Cardiometabolic risk factors, including smoking and male sex, are linked to aortic stenosis. Emerging studies have identified important regulatory roles for immunological and inflammatory responses, including oxidized lipids, various cytokines, and biomineralization. Recent clinical and experimental studies in atherosclerosis and osteoporosis have demonstrated that oxidative stress and oxidized lipids decrease bone formation in the skeletal system while they increase bone formation in the cardiovascular system. Multidisciplinary factors contribute to vascular calcification, including inflammation and metabolic regulation of osteogenesis in the cardiovascular system via similar signaling pathways as bone formation. Calcific aortic valve disease (CAVD) is no longer considered a simple passive process of calcium deposition that occurs with advanced age. Biomineralization in CAVD is a complex, regulated process that involves valvular, circulating, bone marrow-derived cells, macrophage heterogeneity and genetic factors along with biochemical and mechanical factors. The current review will discuss the recently discovered important role of inflammation, metabolic risk factors, and molecular and cellular mechanisms that promote CAVD, as well as the link between osteogenic signals in the skeletal and cardiovascular systems. This may inform future therapeutic strategies for CAVD progression.

Metabolic syndrome epidemic among Korean adults: Korean survey of Cardiometabolic Syndrome (2018).

BACKGROUND AND AIMS: Little information exists on the prevalence of metabolic syndrome (MetS) in Korea since 2007. We aimed to provide up-to-date estimates of the prevalence of MetS and its trend in the general adult population in Korea. METHODS: We compared the prevalence and pattern of MetS among participants in the Korean National Health and Nutrition Examination Surveys (KNHANES) IV (2007-2009), V (2010-2012), and VI (2013-2015), aged ≥19 years. Data from the 2005 census of the Korean population were presented according to age standardization. RESULTS: The overall age-standardized prevalence of MetS in 2013-2015 was 20.3% (95% confidence interval [CI], 19.6%-21%). Since 2007, the overall prevalence of MetS has remained stable, whereas the prevalences among men and women, respectively, have increased and decreased slightly. By contrast, the prevalence of MetS among men aged 19-49 years has shown an increasing tendency since 2007. Moreover, nearly 40% of women aged ≥60 years had MetS in 2013-2015. Among the five components of MetS, only elevated fasting glucose level has shown an increasing trend since 2007 in both men and women. As the family income and educational level decreased, the prevalence of MetS increased. CONCLUSIONS: The overall prevalence of MetS has remained stable since 2007. However, the prevalence of MetS was higher in middle-aged men and women aged ≥60 years. Considering the close association between MetS and socioeconomic status, age- and sex-specific strategies should be developed at the national level for the treatment and prevention of MetS in Korea.