Impaired lung function and lung cancer risk in 461 183 healthy individuals: a cohort study.

BACKGROUND: It has been known that smoking and various lung diseases including lung cancer can cause lung function impairment. However, the impact of different types of lung function impairments, such as preserved ratio impaired spirometry (PRISm) and airflow obstruction (AO), on the incidence and mortality of lung cancer in both general and never-smoker populations remains unclear. We wished to examine the effect of lung function impairments on lung cancer risks. METHODS: This was a retrospective cohort study (1 January 1994 to 31 December 2017) of individuals from a health surveillance programme in Taiwan who underwent baseline spirometry tests at the entry point. PRISm was defined as an FEV1/FVC (forced expiratory volume in 1 s/forced vital capacity) ratio >0.7 and FEV1 <0.8, while AO was defined as an FEV1/FVC ratio <0.7. Cox proportional hazards models and cubic spline curves were used to examine the associations between lung function impairments and lung cancer risks. RESULTS: The study included 461,183 individuals, of whom 14.3% had PRISm and 7.9% had AO. A total of 4038 cases of lung cancer and 3314 lung cancer-related deaths were identified during the 23 years of follow-up. Individuals with PRISm and AO exhibited a higher risk of lung cancer incidence and mortality compared with those with normal lung function. The adjusted HRs and 95% CIs were 1.14 (1.03 to 1.26) and 1.23 (1.10 to 1.37) in the overall cohort, and 1.08 (0.93 to 1.24), and 1.23 (1.05 to 1.45) in the never-smoker cohort. The risks of both developing and dying of lung cancer increased with the severity levels of lung function impairments and lower FEV1 values. CONCLUSION: Impaired lung function is associated with increased risks of developing lung cancer and subsequent mortality. The study highlights the importance of considering lung function in lung cancer screening for better candidate selection.

Systolic blood pressure as a critical mediator in the association between adult height and 25-year risk of stroke.

BACKGROUND: Adult height is associated with the risk of stroke. However, the underlying mechanism remains unclear. We explored the mediating role of metabolic factors in the association between adult height and stroke incidence. METHODS: We used data from 3306 community-dwelling participants with complete information on adult height, metabolic factors, and 25-year cardiovascular outcomes. Participants were classified into three adult height groups based on sex-specific height quartiles: short (Q1), average (Q2-Q3), and tall (Q4). The primary endpoint was the occurrence of cardiovascular disease, including coronary artery disease and stroke. RESULTS: Taller adult height was associated with a lower risk of stroke. Compared with the short group the risk of stroke reduced with taller height with a hazard ratio (HR) of 0.68 in the average group (95% confidence interval [CI]: 0.50-0.93), and 0.45 in the tall group (95% CI: 0.31-0.65). Low systolic blood pressure was considered as a protective mediator in the effect of adult height on the risk of stroke in the average (HR: 0.86; 95% CI: 0.82-0.93) and the tall group (HR: 0.85; 95% CI: 0.78-0.91). Systolic blood pressure significantly contributed to height-related stroke risk (proportion mediated: 0.41; 95% CI: 0.19-1.56). CONCLUSIONS: This study found an inverse association between adult height and stroke risk, which is partly driven by lower systolic blood pressure. These findings highlight the importance of systolic blood pressure management as a potential preventive strategy against stroke.

Mortality risk in patients with preserved ratio impaired spirometry: assessing the role of physical activity.

BACKGROUND: While all-cause mortality is reportedly increased in preserved ratio impaired spirometry (PRISm), no remedial efforts have been suggested. AIM: To study the ability of physical activity (PA) on reducing the morality increased in PRISm patients. DESIGN: We prospectively enrolled a cohort of Taiwanese adults from 1994 to 2018 in a health surveillance program. METHODS: Mortality risks of those who were inactive were compared against those meeting the current recommendation of 150 min/week of physical activity. Cox proportional hazards models were used for hazard ratios and life table method was for estimating loss of life expectancy. RESULTS: A total of 461,183 adults was enrolled. Among them, one seventh of the cohort (65,832 or 14.3%) had PRISm, and 53.1% were inactive. Those who were inactive with PRISm had 28% increased mortality from all-cause, 45% from cardiovascular diseases and 67% from respiratory disease, with a 3-year reduction in life expectancy (males, 3.72 and females, 2.93). In PRISm patients who met the exercise recommendation, excess mortality was reduced by 2/3, both all-cause (from 28% to 9%) and CVD (from 45% to 15%). CONCLUSION: PRISm involves a large portion of general population (14.3%) and shortens life expectancy by 3 years. More than half of the subjects were physically inactive, and adherence to 150 min/week of physical activity was associated with a two-third reduction of excess mortality from all cause and from CVD. Recommending physical activity among those with PRISm might be highly beneficial, although exercise alone may not eliminate all risks associated with PRISm.

Association Between Adequate Serum 25(OH)D Levels and Atherogenic Dyslipidemia in Young Adults.

AIM: This study aimed to investigate the association between vitamin D deficiency and novel biomarkers of atherogenic dyslipidemia among young adults. METHOD: A total of 976 young adults were recruited between 2011 and 2019. Their serum 25(OH)D levels were measured, and lipid profile markers, including low-density lipoprotein cholesterol (LDL-C), low-density lipoprotein triglyceride (LDL-TG), and small-dense low-density lipoprotein cholesterol (sdLDL-C), were assessed as novel biomarkers of atherogenic dyslipidemia. Multivariable linear regression was used to analyze the association between vitamin D levels and lipid profile markers. Odds ratios were calculated to assess the risk of atherogenic dyslipidemia in individuals with serum 25(OH)D levels below 30 ng/mL compared to those with levels above 30 ng/mL. Structural equation modeling (SEM) was employed to explore potential mediation pathways. RESULTS: The study found a significant association between vitamin D levels and lower levels of LDL-C, LDL-TG, sdLDL-C, non-high-density lipoprotein cholesterol (non-HDL-C), triglycerides, and total cholesterol. Individuals with serum 25(OH)D levels below 30 ng/mL exhibited significantly higher odds ratios for developing atherogenic dyslipidemia in a dose-response pattern compared to those with vitamin D levels above 30 ng/mL. Notably, structural equation modeling (SEM) analysis revealed that vitamin D did not affect atherogenic lipid markers through the mediation of insulin resistance markers or high-sensitivity C-reactive protein. CONCLUSION: This study provides evidence of an association between vitamin D deficiency and atherogenic dyslipidemia in young adults. It further highlights that individuals with serum 25(OH)D levels below 30 ng/mL are at a significantly higher risk of developing atherogenic dyslipidemia in a dose-response manner compared to those with higher vitamin D levels. These findings underscore the potential role of vitamin D in dyslipidemia management and emphasize the importance of maintaining sufficient vitamin D levels for cardiovascular health in young adults.

The Association among Urinary Lead and Cadmium, Serum Adiponectin, and Serum Apoptotic Microparticles in a Young Taiwanese Population.

Previous studies reported that lead (Pb) and cadmium (Cd) exposure are linked to changes in serum adiponectin; an adipokine that promotes glycolysis and inhibits gluconeogenesis to regulate glucose metabolism. However, no study has ever explored the relationship between exposure to these two heavy metals and adiponectin in adolescents and young adults. Additionally, the role of adiponectin in the relationship between Pb and Cd exposure and vascular endothelial cell apoptosis has never been investigated. In this study, 724 Taiwanese participants, aged 12 to 30 years, were enrolled to investigate the association among urinary lead and cadmium, serum adiponectin, and apoptotic microparticles (CD31+/CD42a-, CD31+/CD42a+, and CD14). The results of the current study revealed a statistically significant inverse association between urine Pb and Cd levels and adiponectin levels, as well as a positive association with apoptotic microparticles (CD31+/CD42a-, CD31+/CD42a+, and CD14). Adiponectin was also inversely correlated with CD31+/CD42a- and CD31+/CD42a+. Moreover, when subjects with both Pb and Cd levels above the 50th percentile were compared to those below it, the former group exhibited the lowest average adiponectin value. Additionally, a more pronounced positive association between heavy metals and apoptotic microparticles (CD31+/CD42a- and CD31+/CD42a+) was observed when adiponectin levels were lower. Furthermore, an interaction between adiponectin and heavy metals was identified in the relationship between these metals and CD31+/CD42a-. In conclusion, these findings suggest that Pb and Cd exposure may have an adverse effect on adiponectin, and it may play a role in the link between heavy metal exposure and the dysfunction of vascular endothelial cells. Future studies are needed to establish whether a causal relationship exists.

The Association between 4-Tertiary-Octylphenol, Apoptotic Microparticles, and Carotid Intima-Media Thickness in a Young Taiwanese Population.

As one of the most common alkylphenols, 4-tertiary-octylphenol (4-tOP) is commonly used in many consumer products. Our previous epidemiological study revealed a negative correlation between serum 4-tOP levels and carotid intima-media thickness (CIMT), which serves as a biomarker of arteriosclerosis. We aimed to explore the role of apoptotic microparticles, markers of vascular endothelial cell function, in the 4-tOP and CIMT connection. To investigate this, we enrolled 886 Taiwanese adolescents and young adults (aged 12-30 years) and examined the relationships among serum 4-tOP levels, apoptotic microparticles (CD31+/CD42a-, CD31+/CD42a+), and CIMT. Our results showed negative associations among serum 4-tOP levels, both apoptotic microparticles, and CIMT in multiple linear regression analysis. The odds ratios for CIMT (≥75th percentile) and the natural logarithm of 4-tOP were highest when both CD31+/CD42a- and CD31+/CD42a+ were greater than the 50th percentile. Conversely, the odds ratios were lowest when both CD31+/CD42a- and CD31+/CD42a+ were less than the 50th percentile. In the structural equation model, we demonstrated that serum 4-tOP levels were negatively correlated with CIMT and indirectly and negatively correlated with CIMT through both apoptotic microparticles. In conclusion, our study reported the inverse association between 4-tOP apoptotic microparticles and CIMT in a young Taiwanese population. Further experimental studies are needed to clarify these associations.

Urban climate and cardiovascular health: Focused on seasonal variation of urban temperature, relative humidity, and PM2.5 air pollution.

Seasonal effects on subclinical cardiovascular functions (CVFs) are an important emerging health issue for people living in urban environment. The objectives of this study were to demonstrate the effects of seasonal variations of temperature, relative humidity, and PM2.5 air pollution on CVFs. A total of 86 office workers in Taipei City were recruited, their arterial pressure waveform was recorded by cuff sphygmomanometer using an oscillometric blood pressure (BP) device for CVFs assessment. Results of paried t-test with Bonferroni correction showed significantly increased systolic and diastolic BP (SBP, DBP), central end-systolic and diastolic BP (cSBP, cDBP) and systemic vascular resistance, but decreased heart rate (HR), stroke volume (SV), cardio output (CO), and cardiac index in winter compared with other seasons. After controlling for related confounding factors, SBP, DBP, cSBP, cDBP, LV dp/dt max, and brachial-ankle pulse wave velocity (baPWV) were negatively associated with, and SV was positively associated with seasonal temperature changes. Seasonal changes of air pollution in terms of PM2.5 were significantly positively associated with DBP and cDBP, as well as negatively associated with HR and CO. Seasonal changes of relative humidity were significantly negatively associated with DBP, and cDBP, as well as positively associated with HR, CO, and baPWV. This study provides evidence of greater susceptibility to cardiovascular events in winter compared with other seasons, with ambient temperature, relative humidity, and PM2.5 as the major factors of seasonal variation of CVFs.

Benefits and Harms of COVID-19 Vaccines in Cardiovascular Disease: A Comprehensive Review.

Patients with a history of cardiovascular disease (CVD) who contract coronavirus disease 2019 (COVID-19) tend to have a worse prognosis and more severe cardiovascular side effects. COVID-19 vaccines, which are intended to prevent COVID-19, may also potentially reduce the severity and complications (including cardiovascular sequelae) of COVID-19, especially in patients with a history of CVD. However, there have also been reports of cardiovascular side effects from COVID-19 vaccines of various brands and types. The purpose of this study is to review the benefits and harms of COVID-19 vaccines in relation to CVD. In this thorough review of the most current evidence on the benefits and harms of COVID-19 vaccines, we present information about the characteristics of cardiovascular complications. Most of the evidence focuses on myocarditis or pericarditis, which are most strongly associated with mRNA vaccines and predominantly occur in young males within days of receiving the second dose. Meanwhile, post-vaccination myocardial infarction is more common in older males, and the first dose of adenoviral vector vaccines appears to play a greater role in this complication. This information may guide us in formulating alternative options and implementing targeted surveillance. Gaining more knowledge about the potential benefits and harms of COVID-19 vaccines will improve our ability to make informed decisions and judgments about the balance of these factors.

Novel Selective PPARα Modulator Pemafibrate for Dyslipidemia, Nonalcoholic Fatty Liver Disease (NAFLD), and Atherosclerosis.

Statins, the intestinal cholesterol transporter inhibitor (ezetimibe), and PCSK9 inhibitors can reduce serum LDL-C levels, leading to a significant reduction in cardiovascular events. However, these events cannot be fully prevented even when maintaining very low LDL-C levels. Hypertriglyceridemia and reduced HDL-C are known as residual risk factors for ASCVD. Hypertriglyceridemia and/or low HDL-C can be treated with fibrates, nicotinic acids, and n-3 polyunsaturated fatty acids. Fibrates were demonstrated to be PPARα agonists and can markedly lower serum TG levels, yet were reported to cause some adverse effects, including an increase in the liver enzyme and creatinine levels. Recent megatrials of fibrates have shown negative findings on the prevention of ASCVD, which were supposed to be due to their low selectivity and potency for binding to PPAR α. To overcome the off-target effects of fibrates, the concept of a selective PPARα modulator (SPPARMα) was proposed. Kowa Company, Ltd. (Tokyo, Japan), has developed pemafibrate (K-877). Compared with fenofibrate, pemafibrate showed more favorable effects on the reduction of TG and an increase in HDL-C. Fibrates worsened liver and kidney function test values, although pemafibrate showed a favorable effect on liver function test values and little effect on serum creatinine levels and eGFR. Minimal drug-drug interactions of pemafibrate with statins were observed. While most of the fibrates are mainly excreted from the kidney, pemafibrate is metabolized in the liver and excreted into the bile. It can be used safely even in patients with CKD, without a significant increase in blood concentration. In the megatrial of pemafibrate, PROMINENT, for dyslipidemic patients with type 2 diabetes, mild-to-moderate hypertriglyceridemia, and low HDL-C and LDL-C levels, the incidence of cardiovascular events did not decrease among those receiving pemafibrate compared to those receiving the placebo; however, the incidence of nonalcoholic fatty liver disease was lower. Pemafibrate may be superior to conventional fibrates and applicable to CKD patients. This current review summarizes the recent findings on pemafibrate.

The role of angiotensin I-converting enzyme gene polymorphism and global DNA methylation in the negative associations between urine di-(2-ethylhexyl) phthalate metabolites and serum adiponectin in a young Taiwanese population.

BACKGROUND: Adiponectin is a key protein produced in adipose tissue, with crucial involvement in multiple metabolic processes. Di-(2-ethylhexyl) phthalate (DEHP), one of the phthalate compounds used as a plasticizer, has been shown to decrease adiponectin levels in vitro and in vivo studies. However, the role of angiotensin I-converting enzyme (ACE) gene polymorphism and epigenetic changes in the relationship between DEHP exposure and adiponectin levels is not well understood. METHODS: This study examined the correlation between urine levels of DEHP metabolite, epigenetic marker 5mdC/dG, ACE gene phenotypes, and adiponectin levels in a sample of 699 individuals aged 12-30 from Taiwan. RESULTS: Results showed a positive relationship between mono-2-ethylhexyl phthalate (MEHP) and 5mdC/dG, and a negative association between both MEHP and 5mdC/dG with adiponectin. The study found that the inverse relationship between MEHP and adiponectin was stronger when levels of 5mdC/dG were above the median. This was supported by differential unstandardized regression coefficients (- 0.095 vs. - 0.049, P value for interaction = 0.038)). Subgroup analysis also showed a negative correlation between MEHP and adiponectin in individuals with the I/I ACE genotype, but not in those with other genotypes, although the P value for interaction was borderline significant (0.06). The structural equation model analysis indicated that MEHP has a direct inverse effect on adiponectin and an indirect effect via 5mdC/dG. CONCLUSIONS: In this young Taiwanese population, our findings suggest that urine MEHP levels are negatively correlated with serum adiponectin levels, and epigenetic modifications may play a role in this association. Further study is needed to validate these results and determine causality.

Corrigendum: Systolic blood pressure as the mediator of the effect of early menarche on the risk of coronary artery disease: A Mendelian randomization study.

[This corrects the article DOI: 10.3389/fcvm.2022.1023355.].

Cardiovascular physiological effects of balneotherapy: focused on seasonal differences.

Hot water bathing has been demonstrated to be an effective way to improve people's cardiovascular health in many studies. This study focused on seasonal physiological changes to provide suggestions on bathing methods based on season for hot spring bathing. Volunteers were recruited to the program of hot spring bathing at 38-40 °C in New Taipei City. Cardiovascular function, blood oxygen, and ear temperature were observed. There were five assessments for each participant during the study process: baseline, bathing for 20 min and 2 cycles *20 (2*20) min, resting for 20 min and 2*20 min after bathing, respectively. Lower blood pressure (p < 0.001), pulse pressure (p < 0.001), left ventricular dP/dt Max (p < 0.001), and cardiac output (p < 0.05) were identified after bathing then rested for 2*20 min in four seasons, compared to baseline by paired T test. However, in multivariate linear regression model, potential risk for bathing in summer was assumed by higher heart rate (+28.4%, p < 0.001), cardiac output (+54.9%, p < 0.001) and left ventricular dP/dt Max (+27.6%, p < 0.05) during bathing at 2*20 min in summer. Potential risk for bathing in winter was postulated by blood pressure lowering (cSBP -10.0%; cDBP -22.1%, p < 0.001) during bathing at 2*20 min in winter. Hot spring bathing is shown to potentially improve cardiovascular function via reducing cardiac workload and vasodilation effects. Prolonged hot spring bathing in summer is not suggested due to significantly increased cardiac stress. In winter, prominent drop of blood pressure should be concerned. We demonstrated the study enrollment, the hot-spring contents and location, and physiological changes of general trends or seasonal variations, which may indicate potential benefits and risks during and after bathing. (Abbreviations: BP, blood pressure; PP, pulse pressure; LV, left ventricular; CO, cardiac output; HR, heart rate; cSBP, central systolic blood pressure; cDBP, central diastolic blood pressure).

Glycative Stress, Glycated Hemoglobin, and Atherogenic Dyslipidemia in Patients with Hyperlipidemia.

(1) Background: Diabetes mellitus (DM) is a significant health problem and is associated with dyslipidemia; however, the association between glycative stress, in terms of glycated hemoglobin (HbA1c), and atherogenic dyslipidemia in hyperlipidemic patients with and without DM has rarely been reported. (2) Methods: We prospectively recruited 949 hyperlipidemic patients from the Lipid Clinic of the National Taiwan University Hospital. HbA1c and fasting serum lipids, including total cholesterol (TC), high- and low-density lipoprotein cholesterol (HDL-C and LDL-C), small dense LDL-C (sdLDL-C), very low-density lipoprotein cholesterol (VLDL-C), triglycerides, and advanced glycation end-products (AGEs), were measured. After fasting for 10-14 h, all subjects except those with DM underwent a standard oral glucose tolerance test (OGTT) with 75 g of glucose loading. All subjects were asked to discontinue the use of lipid-lowering agents for 8 weeks before recruitment. (3) Results: Patients with DM had a higher prevalence of hypertension and higher levels of triglyceride, TC/HDL-C ratio, AGEs, VLDL-C, and sdLDL-C. Among patients with higher HbA1c, the serum VLDL-C, AGEs, and TC/HDL-C ratio were significantly higher than those with lower HbA1c. After adjustment for covariates, multiple logistic regression analyses revealed different groups of dysglycemia with higher HbA1c had a higher odds ratio for TC/HDL-C ≥ 5, sdLDL-C ≥ 75th percentile, VLDL-C ≥ 75th percentile and AGEs ≥ 75th percentile. (4) Conclusions: A higher HbA1c was associated with a significant increase in the risk of atherogenic dyslipidemia and AGEs levels in patients with hyperlipidemia. The findings can be very promising in clinical application.

Association of Urinary Lead and Cadmium Levels, and Serum Lipids with Subclinical Arteriosclerosis: Evidence from Taiwan.

BACKGROUND: Exposure to lead and cadmium has been linked to changes in lipid metabolism and the development of arteriosclerosis, but the role of lipoprotein profiles in this relationship is not well understood, including the potential role of novel lipid biomarkers. METHODS: In this study, we enrolled 736 young Taiwanese subjects aged 12 to 30 years to assess the correlation between urine levels of lead and cadmium, lipoprotein profiles, and carotid intima-media thickness (CIMT). RESULTS: Higher levels of lead and cadmium were significantly associated with higher levels of low-density lipoprotein cholesterol (LDL-C), small dense LDL-C (sdLDL-C), LDL-triglyceride (LDL-TG), and CIMT. Participants with higher levels of lead and cadmium had the highest mean values of CIMT, LDL-C, sdLDL-C, and LDL-TG. In a structural equation model, lead had a direct and indirect association with CIMT through LDL-C and sdLDL-C, whereas cadmium had a direct association with CIMT and an indirect association through LDL-C. CONCLUSION: Our results suggest higher levels of lead and cadmium are associated with abnormal lipid profiles and increased CIMT. These heavy metals could have additive effects on lipids and CIMT, and the relationship between them may be mediated by lipoprotein levels. Further research is needed to determine the causal relationship.

Epidemiological Characteristics and Meteorological Factors of Sudden Death among General Population of Ethnic Chinese in Taiwan: An Eighteen-Year Follow-Up Report in a Community.

Background: The epidemiological characteristics of sudden death may vary according to ethnicity and country. This study aimed to analyze the distribution of sudden deaths in Taiwan, as well as their epidemiological characteristics and the associated meteorological factors. Methods: The Chin-Shan Community Cardiovascular Cohort is a longitudinal study conducted in a community in Taipei County since July 1990. A total of 3,602 individuals aged 35 years and older were included in the study. Sudden deaths were prospectively recorded and analyzed. Results: Eighty-two (68.3% men) sudden deaths (8.56% of all deaths) were reported from July 1990 to December 2008, of which 87.8% were caused by cardiovascular disease. However, only 36.6% were attributed to coronary artery disease. There was a higher incidence of sudden death in the winter [incidence rate ratio (IRR): 1.91, 95% confidence interval (CI): 1.42-2.56], compared to fall, and the highest peak of sudden death occurred between 16:00-20:00 (IRR: 3.00, 95% CI: 1.72-5.22) compared to 00:00-04:00 as the reference group. Additionally, a relatively higher mean temperature was associated with a lower risk of sudden death (IRR: 0.96, 95% CI: 0.93-0.98). On the other hand, higher humidity (IRR: 1.09, 95% CI: 1.02-1.16) and discomfort index (IRR: 1.03, 95% CI: 1.003-1.05) were associated with increased risks of sudden death. Conclusions: Meteorological factors and circadian patterns were associated with sudden death among our Taiwanese cohort. Our study findings may support potential protective behavior for sudden death via weather forecasting.

2023 Guidelines of the Taiwan Society of Cardiology on the Diagnosis and Management of Chronic Coronary Syndrome.

Coronary artery disease (CAD) covers a wide spectrum from persons who are asymptomatic to those presenting with acute coronary syndromes (ACS) and sudden cardiac death. Coronary atherosclerotic disease is a chronic, progressive process that leads to atherosclerotic plaque development and progression within the epicardial coronary arteries. Being a dynamic process, CAD generally presents with a prolonged stable phase, which may then suddenly become unstable and lead to an acute coronary event. Thus, the concept of "stable CAD" may be misleading, as the risk for acute events continues to exist, despite the use of pharmacological therapies and revascularization. Many advances in coronary care have been made, and guidelines from other international societies have been updated. The 2023 guidelines of the Taiwan Society of Cardiology for CAD introduce a new concept that categorizes the disease entity according to its clinical presentation into acute or chronic coronary syndromes (ACS and CCS, respectively). Previously defined as stable CAD, CCS include a heterogeneous population with or without chest pain, with or without prior ACS, and with or without previous coronary revascularization procedures. As cardiologists, we now face the complexity of CAD, which involves not only the epicardial but also the microcirculatory domains of the coronary circulation and the myocardium. New findings about the development and progression of coronary atherosclerosis have changed the clinical landscape. After a nearly 50-year ischemia-centric paradigm of coronary stenosis, growing evidence indicates that coronary atherosclerosis and its features are both diagnostic and therapeutic targets beyond obstructive CAD. Taken together, these factors have shifted the clinicians' focus from the functional evaluation of coronary ischemia to the anatomic burden of disease. Research over the past decades has strengthened the case for prevention and optimal medical therapy as central interventions in patients with CCS. Even though functional capacity has clear prognostic implications, it does not include the evaluation of non-obstructive lesions, plaque burden or additional risk-modifying factors beyond epicardial coronary stenosis-driven ischemia. The recommended first-line diagnostic tests for CCS now include coronary computed tomographic angiography, an increasingly used anatomic imaging modality capable of detecting not only obstructive but also non-obstructive coronary plaques that may be missed with stress testing. This non-invasive anatomical modality improves risk assessment and potentially allows for the appropriate allocation of preventive therapies. Initial invasive strategies cannot improve mortality or the risk of myocardial infarction. Emphasis should be placed on optimizing the control of risk factors through preventive measures, and invasive strategies should be reserved for highly selected patients with refractory symptoms, high ischemic burden, high-risk anatomies, and hemodynamically significant lesions. These guidelines provide current evidence-based diagnosis and treatment recommendations. However, the guidelines are not mandatory, and members of the Task Force fully realize that the treatment of CCS should be individualized to address each patient's circumstances. Ultimately, the decision of healthcare professionals is most important in clinical practice.

Association between Wakeup Frequency at Night and Atherogenic Dyslipidemia: Evidence for Sex Differences.

AIM: This study aimed to determine whether sleep disturbance, defined as the wakeup frequency at night, is associated with atherogenic dyslipidemia and to explore possible sex differences. METHODS: A total of 1,368 adults aged 19-70 years were included in the study of lifestyles and atherogenic dyslipidemia at the National Taiwan University Hospital in the period of 2008-2012. They completed a questionnaire regarding lifestyle information and sleep quality, including sleep hour duration, use of sleeping pills, and wakeup frequency during nighttime sleep. The measured lipid profiles included total cholesterol, triglycerides, low- and high-density lipoprotein cholesterol (LDL-C and HDL-C, respectively), non-HDL-C, and small dense LDL-C (sdLDL-C). Multivariate logistic regression was performed to determine habitual interrupted sleep and the odds ratio of atherogenic dyslipidemia following adjustment for conventional risk factors and for sex-based subgroup analysis. RESULTS: A wakeup frequency ≥ 3 times per night was independently associated with an increased risk [odds ratio (95% confidence interval)] of dyslipidemia was 1.96 (1.17-3.28), and non-HDL-C ≥ 160 mg/dL was 1.78 (1.09-2.89). A higher wakeup frequency was associated with increased atherogenic dyslipidemia in women than in men. The multivariate adjusted relative risks for non-HDL ≥ 160 mg/dL and cholesterol ≥ 200 mg/dL were 3.05 (1.27-7.34) and 4.01(1.29-12.45) for female individuals with insomnia and those with a wakeup frequency ≥ 2 times per night, respectively. CONCLUSION: A higher wakeup frequency was associated with atherogenic dyslipidemia in Taiwanese adults, particularly in women. This study also provided another evidence of increasing cardiovascular diseases in subjects with habitual interrupted sleep.

Recommendations for ventilation of remodeled negative-pressure isolation wards for COVID-19 patients: A comparison of international guidelines.

This mini-review provides the practice guideline recommendations for ventilation of remodeled negative-pressure isolation wards for COVID-19 Patients. Remodeled "quasi-negative-pressure" isolation wards had been proved a feasible, inexpensive, safe, and effective measure to contain nosocomial outbreaks. We should first determine the minimum required ventilation volume of an isolation ward based on the severity of COVID-19 patients. Mechanical ventilation remains the mainstay for achieving the requirement, while the assistance of recirculation is also helpful. Beyond adequate ventilation volume, the "clean to less-clean" directional airflow remains the golden rule for the solution of indoor ventilation. The virus-laden exhaust should be treated with HEPA/UV device or be kept away from living organisms, buildings, and air inlets.

Hospital Occupational Health Service Network and Reporting Systems in Taiwan From 2008 to 2021.

OBJECTIVE: To evaluate the provision of occupational health services at hospitals following the establishment of the Network of Occupational Disease and Injury Service in 2007. METHODS: A review of occupational health services during 2008 to 2021 was conducted. The medical practice-based reporting system was compared with the database of compensated occupational diseases (ODs) from Taiwan's Labor Insurance. RESULTS: First-time outpatient visits for occupational evaluation and total visits to Network of Occupational Disease and Injury Service health care institutions increased from 1777 and 9435 to 12,092 and 23,210, respectively. Reported ODs increased from 1626 to 2043 with a peak of 2791. Up to 1380 workers evaluated for work resumption in 2021. Similar to the increasing trend in reported ODs, the number of compensated ODs increased over years. CONCLUSION: The health service needs of Taiwanese workers from OD evaluation to vocational rehabilitation are increasing.

Familial Hypercholesterolemia and Lipoprotein(a): A Gordian Knot in Cardiovascular Prevention.

Familial hypercholesterolemia (FH) is the most frequent genetic disorder resulting in increased low-density lipoprotein cholesterol (LDL-C) levels from childhood, leading to premature atherosclerotic cardiovascular disease (ASCVD) if left untreated. FH diagnosis is based on clinical criteria and/or genetic testing and its prevalence is estimated as being up to 1:300,000−400,000 for the homozygous and ~1:200−300 for the heterozygous form. Apart from its late diagnosis, FH is also undertreated, despite the available lipid-lowering therapies. In addition, elevated lipoprotein(a) (Lp(a)) (>50 mg/dL; 120 nmol/L), mostly genetically determined, has been identified as an important cardiovascular risk factor with prevalence rate of ~20% in the general population. Novel Lp(a)-lowering therapies have been recently developed and their cardiovascular efficacy is currently investigated. Although a considerable proportion of FH patients is also diagnosed with high Lp(a) levels, there is a debate whether these two entities are associated. Nevertheless, Lp(a), particularly among patients with FH, has been established as a significant cardiovascular risk factor. In this narrative review, we present up-to-date evidence on the pathophysiology, diagnosis, and treatment of both FH and elevated Lp(a) with a special focus on their association and joint effect on ASCVD risk.