Lower Cardiovascular Disease Mortality Research Articles

Trends in Regional Disparity in Cardiovascular Mortality in Korea, 1983-2019.

Despite remarkable reduction in cardiovascular disease (CVD) mortality, the burden has remained the leading cause of death. Since little research has focused on regional disparity in CVD mortality, this study aims to investigate its spatiotemporal trends in Korea from 1983 to 2019. Using the causes of death statistics in Korea, we analyzed the geographic variation in deaths from CVDs from 1983 to 2019. The sex and age-standardized mortality rate was calculated according to the 17 administrative regions. The analyses include all diseases of the circulatory system (International Classification of Diseases-10 codes, I00-I99), along with the following 6 subcategories which were not mutually exclusive: total heart disease (I00-I13 and I20-I51), hypertensive heart disease (I10-I13), ischemic heart disease (I20-I25), myocardial infarction (I21-I23), heart failure (I50), and cerebrovascular disease (I60-I69). Overall, heart failure death rate increased across all regions, and other CVD death rates showed a decreasing trend. Regional disparity in mortality was substantial in the early 1980s but converged over time. In all types of cardiovascular mortality, Busan, Ulsan and Gyeongnam remained the highest, although they showed a downward trend like other regions. Jeju continued to have a relatively low CVD mortality rate. The regional disparity substantially decreased compared to the 1980s. However, the relatively high burden of CVD mortality in the southeastern region has not been fully resolved.

Association of cardiovascular health with mortality among COPD patients: National Health and Nutrition Examination Survey III

BackgroundAll-cause and cardiovascular disease (CVD) mortality are higher among patients with chronic obstructive pulmonary disease (COPD). We examined the association between American Heart Association's Life's Simple 7 (LS7) metrics and all-cause as well as CVD mortality in patients with COPD. MethodsWe examined 1513 US adults with COPD aged ≥ 40, without prior CVD, from the National Health and Nutrition Examination Survey III. COPD was defined as FEV1/FVC<0.7 in absence of asthma. Adjusted Cox regression was used to assess the relation of LS7 metrics with all-cause and CVD mortality. ResultsOverall, only 74 participants (4.9%) had ideal 5-7 LS7 metrics. Over a mean follow-up of 14.2±7.9 years, 1162 individuals died, of which 315 were due to CVD. Age, sex, and ethnicity-adjusted HRs (95% CI) for all-cause mortality were 0.53 (0.41-0.68), 0.45 (0.34-0.59), 0.66 (0.49-0.87) and 0.75 (0.56-1.00) among those with ideal vs poor control of smoking, diet, physical activity and fasting blood glucose, respectively. However, the ideal and intermediate LS7 metrics were not significantly associated with lower risk of CVD mortality, except for a BMI between 25-29.9 kg/m2. Those with 5-7 vs 0-1 ideal metrics had adjusted HRs 0.50 (0.40-0.87) for all-cause and 0.53 (0.21-1.36) for CVD mortality. ConclusionIdeal levels of multiple behavioral and health factors are associated with substantially lower risks for all-cause mortality, with a trend for lower CVD mortality among US adults with COPD.

Survival and Death Causes in Thyroid Cancer in Taiwan: A Nationwide Case-Control Cohort Study.

Simple SummaryThis study aims to evaluate overall survival and the risk of cause-specific mortality of thyroid cancer patients. Thyroid cancer patients were obtained from the universal health insurance claims from Taiwan between 2001 and 2017. We compared these patients with control subjects matched for age, gender, and baseline conditions to assess the risk of mortality. Of the 30,778 patients with thyroid cancer, the overall mortality rate was 1.29% and the leading causes of death were thyroid cancer (31.2%), other cancers (29.9%), and cardiovascular disease (CVD) mortality (12.3%), respectively. We found patients with thyroid cancer had excellent overall survival and lower CVD mortality risk.The incidence of thyroid cancer has increased substantially worldwide. However, the overall mortality risk and actual causes of death in thyroid cancer patients have not been extensively evaluated. In this study, patients with thyroid cancer diagnosed between 2001 and 2017 were analyzed from Taiwan’s National Health Insurance Research Database. We compared these patients with control subjects matched for age, gender, history of cardiovascular disease (CVD), hyperlipidemia, diabetes mellitus, hypertension, and occupation to assess the risk of overall mortality and cause-specific mortality. Finally, our cohort comprised 30,778 patients with thyroid cancer. Three hundred and ninety-eight deaths (1.29%) occurred during a median follow-up of 60.0 months (range: 30.3 to 117.6 months). The primary cause of death was thyroid cancer mortality (31.2%), followed by other malignancy-related mortality (29.9%) and CVD mortality (12.3%). The overall mortality risk was similar between the thyroid cancer and control groups (unadjusted hazard ratio (HR): 0.98; 95% confidence interval (CI): 0.88–1.10); the adjusted HR was 1.07 (95% CI: 0.95–1.20) after multivariate adjustment for age, gender, history of CVD, hyperlipidemia, diabetes mellitus, hypertension, and occupation. The risk of other malignancy-related mortality was comparable between two groups. CVD mortality risk was lower in the thyroid cancer group, with an unadjusted HR of 0.51 (95% CI: 0.38–0.69) and adjusted HR of 0.56 (95% CI: 0.42–0.76). In conclusion, patients with thyroid cancer had excellent overall survival. Thyroid cancer-specific mortality was the leading cause of death, highlighting the importance of thyroid cancer management. Thyroid cancer patients had lower CVD mortality risk than the general population.

Women Have Lower Mortality Than Men After Attending a Long-Term Medically Supervised Exercise Program.

Medically supervised exercise programs (MSEPs) are equally recommended for men and women with cardiovascular disease (CVD). Aware of the lower CVD mortality in women, we hypothesized that among patients attending a MSEP, women would also have better survival. Data from men and women, who were enrolled in a MSEP between 1994 and 2018, were retrospectively analyzed. Sessions included aerobic, resistance, flexibility and balance exercises, and cardiopulmonary exercise test was performed. Date and underlying cause of death were obtained. Kaplan-Meier methods and Cox proportional hazards regression were used for survival analysis. A total of 2236 participants (66% men, age range 33-85 yr) attended a median of 52 (18, 172) exercise sessions, and 23% died during 11 (6, 16) yr of follow-up. In both sexes, CVD was the leading cause of death (39%). Overall, women had a more favorable clinical profile and a longer survival compared to men (HR = 0.71: 95% CI, 0.58-0.85; P < .01). When considering those with coronary artery disease and similar clinical profile, although women had a lower percentage of sex- and age-predicted maximal oxygen uptake at baseline than men (58 vs 78%; P < .01), after adjusting for age, women still had a better long-term survival (HR = 0.68: 95% CI, 0.49-0.93; P = .02). Survival after attendance to a long-term MSEP was better among women, despite lower baseline cardiorespiratory fitness. Future studies should address whether men and women would similarly benefit when participating in an MSEP.

Higher COVID-19 outbreak in countries with lower cardiovascular disease mortality, in Europe

The aim of this work was to evaluate, from an epidemiological perspective, whether there is any association between CVD burden and COVID-19 morbidity and mortality, in EU/EEA and UK. A strong, inverse relationship between COVID-19 and CVD death rates in EU/EEA and UK was observed and presented for the first time in the literature. This relationship was independent of various socio-demographic and lifestyle indicators that may acted as potential confounders.

Green space and cardiovascular health in people with type 2 diabetes.

Associations between green space type and 9-year risk of incident cardiovascular disease (CVD) hospitalisations and deaths were analysed in 4166 people with type 2 diabetes in the Sax Institute's 45 and Up Study. Incidence of all-cause mortality, cardiovascular mortality, fatal or non-fatal CVD events and acute myocardial infarctions (AMI) were 14.67%, 7.23%, 47.36%, and 4.51%, respectively. After full adjustment, more tree canopy was associated with lower CVD mortality, lower fatal or non-fatal CVD events, and lower AMI risk. More open grass was associated with lower all-cause mortality, lower CVD mortality and lower fatal or non-fatal CVD events, but higher AMI risk.

Insurance disparity in cardiovascular mortality among non-elderly cancer survivors

BackgroundInsurance status plays a vital role in cancer diagnosis, treatments and survival. Cancer patients have higher cardiovascular disease (CVD) mortality than the general population.MethodsThe Surveillance, Epidemiology and End Results (SEER) program 2007–2016 was used to estimate the CVD mortality among cancer patients aged 18 to 64 years at the time of diagnosis of an initial malignancy with the eight most prevalent cancers. Standardized mortality ratios (SMRs) were calculated for each insurance (Non-Medicaid vs Medicaid vs Uninsured) using coded cause of death from CVD with adjustment of age, race, and gender. The Fine-Grey Model was used to estimate adjusted Hazard Ratios (HR) of each insurance in CVD mortality.ResultsA total of 768,055 patients were included in the final analysis. CVD death in patients with Medicaid insurance remained higher than in those with Non-Medicaid insurance (HR = 1.71; 95%CI, 1.61–1.81; p < 0.001). Older age, male gender, and black race were all associated with increased CVD mortality in the multivariable model. Compared to the general population, patients with Medicaid had the highest SMRs of CVD mortality, regardless of year of cancer diagnosis, follow-up time, cancer site, and race. Non-Medicaid insured patients had similar CVD mortality to the general population after 2 years out from their cancer diagnosis.ConclusionCancer patients with Non-Medicaid insurance have significantly lower CVD mortality than those with no insurance or Medicaid. The insurance disparity remained significant regardless of type of CVD, cancer site, year of diagnosis and follow-up time.

Sex Differences in the Association of Body Composition and Cardiovascular Mortality.

BackgroundTo determine whether differences in body composition contribute to sex differences in cardiovascular disease (CVD) mortality, we investigated the relationship between components of body composition and CVD mortality in healthy men and women.Methods and ResultsDual energy x‐ray absorptiometry body composition data from the National Health and Nutrition Examination Survey 1999–2004 and CVD mortality data from the National Health and Nutrition Examination Survey 1999–2014 were evaluated in 11 463 individuals 20 years of age and older. Individuals were divided into 4 body composition groups (low muscle mass–low fat mass—the referent; low muscle–high fat; high muscle–low fat, and high muscle–high fat), and adjusted competing risks analyses were performed for CVD versus non‐CVD mortality. In women, high muscle/high fat mass was associated with a significantly lower adjusted CVD mortality rate (hazard ratio [HR], 0.58; 95% CI, 0.39–0.86; P=0.01), but high muscle/low fat mass was not. In men, both high muscle–high fat (HR, 0.74; 95% CI, 0.53–1.04; P=0.08) and high muscle–low fat mass (HR, 0.40; 95% CI, 0.21–0.77; P=0.01) were associated with lower CVD. Further, in adjusted competing risks analyses stratified by sex, the CVD rate in women tends to significantly decrease as normalized total fat increase (total fat fourth quartile: HR, 0.56; 95% CI, 0.34–0.94; P<0.03), whereas this is not noted in men.ConclusionsHigher muscle mass is associated with lower CVD and mortality in men and women. However, in women, high fat, regardless of muscle mass level, appears to be associated with lower CVD mortality risk. This finding highlights the importance of muscle mass in healthy men and women for CVD risk prevention, while suggesting sexual dimorphism with respect to the CVD risk associated with fat mass.

Relation of Absence of Coronary Artery Calcium to Cardiovascular Disease Mortality Risk Among Individuals Meeting Criteria for Statin Therapy According to the 2018/2019 ACC/AHA Guidelines

The 2013 American College of Cardiology and the American Heart Association (ACC/AHA) guidelines resulted in broad recommendations for preventive statin therapy allocation in patients without known cardiovascular disease (CVD). Subsequent studies demonstrated significant heterogeneity of atherosclerotic cardiovascular disease risk across the primary prevention population. In 2018/2019, the guidelines were revised to optimize risk assessment and cholesterol management. We sought to evaluate the heterogeneity of risk in statin-recommended patients, using coronary artery calcium (CAC) according to 2018/2019 ACC/AHA guidelines in a primary prevention cohort. We evaluated 5,800 statin-naive patients aged 40 to 75 years without known coronary heart disease from the Cedars-Sinai Medical Center study cohort. All participants underwent clinical CAC scoring for risk stratification and were followed for all-cause and CVD-specific mortality. A total of 181 deaths occurred including 54 CVD deaths over a follow-up of 9.5 years. Overall, 1,939 participants would have been recommended statin therapy, 32% of whom had no detectable CAC. CAC = 0 participants had the lowest all-cause and CVD mortality rates in both statin-recommended and nonrecommended groups (0.2 and 0.4 CVD deaths per 1,000 person-years, respectively). Absence of CAC in statin-naive patients portends an approximately 12-fold lower CVD mortality (0.2% vs 2.4%) in those recommended for statin therapy compared with any CAC present. In conclusion, in a cohort of patients meeting the 2018/2019 ACC/AHA guidelines for statin therapy for primary prevention, there was a marked heterogeneity of CAC scores, with about one-third of the statin recommended population having no detectable CAC (CAC = 0) with a significantly lower CVD mortality compared with CAC>0.

Whole-Food Low-Protein Plant-Based Nutrition to Prevent or Slow Progression of Chronic Kidney Disease

Whole-Food Low-Protein Plant-Based Nutrition to Prevent or Slow Progression of Chronic Kidney Disease

P1399SPARING EFFECT OF PERITONEAL DIALYSIS VS HEMODIALYSIS ON CHANGE OF BONE MINERAL DENSITY EVALUATED BY WHOLE-BODY DXA AFTER INITIATION OF DIALYSIS THERAPY AND ITS IMPACT ON CLINICAL OUTCOME

Abstract Background and Aims Bone loss is associated with progression of cardiac calcification and increased mortality in end stage renal disease (ESRD) patients but the relations and underlying causes are unclear. We investigated factors associated with changes of bone mineral density (BMD) during the first year after initiation of dialysis and the association between BMD changes and subsequent mortality in ESRD patients. Method In a prospective study of 242 ESRD patients (median age 55 years, 61% men) starting dialysis, total BMD and BMD at specific bone sites (including seven subregions: head, arms, legs, trunk, hip, pelvis and spine) was assessed by whole body dual-energy X-ray absorptiometry (DXA) at baseline and one year after dialysis start. Framingham cardiovascular disease (CVD) risk score, body composition, nutritional status, handgrip strength, various biochemical biomarkers (white blood cell, hemoglobin, albumin, creatinine, calcium, phosphate, intact parathyroid hormone, triglyceride, cholesterol, HDL cholesterol and high-sensitivity C-reactive protein) were recorded. We used multivariate linear regression analysis for BMD change analysis. We followed patients from 12 months after initiating of dialysis until renal transplantation, death or end of 60 months follow-up. During follow-up, 59 patients (24%) died due to CVD (n=33) or other causes (n=26) and 95 patients (39%) underwent renal transplantation. Fine and Gray competing risk analysis was used to ascertain associations of BMD changes with all-cause and CVD-related mortality. Results From baseline to one year after initiation of dialysis, there was a significant decrease of BMDtotal and BMDleg, trunk, rib, pelvis and spine in hemodialysis (HD) patients, whereas no difference was seen in peritoneal dialysis (PD) patients. In multivariate linear regression analysis adjusting for several confounders, HD therapy - compared to PD therapy - was significantly associated with negative changes in BMDtotal (β=-0.15), BMDhead (β=-0.14), BMDleg (β=-0.18) and BMDtrunk (β=-0.16). The direction and extent of changes in BMD, i.e. increase of BMD, associated with statistically significant lower all-cause mortality risk for BMDtotal (sHR, 0.91), BMDhead (sHR 0.91) and BMDleg (sHR 0.92), while for CVD-mortality a significant association with BMD changes was found only for changes in BMDhead (sHR 0.92). Conclusion In patients starting on dialysis, PD therapy appeared to have a beneficial effect on BMD changes as compared to HD during the first year of dialysis therapy. This difference may have implications for clinical outcomes as the degree of bone loss was associated with subsequent mortality. Changes towards increased BMDtotal, BMDhead and BMDleg associated with lower all-cause mortality. For head region – which is known as a cortical bone rich site – positive BMD change associated also with lower CVD mortality suggesting that increase or maintenance of BMD of cortical bone rich sites may have stronger association with clinical outcome in ESRD than BMD of trabecular bone.

Coronary Artery Calcium and the Age-Specific Competing Risk of Cardiovascular Versus Cancer Mortality: The Coronary Artery Calcium Consortium

BackgroundCoronary artery calcium (CAC) is a guideline recommended cardiovascular disease (CVD) risk stratification tool that increases with age and is associated with non-cardiovascular disease outcomes including cancer. We sought to define the age-specific change in the association between CAC and cause-specific mortality. MethodsThe Coronary Artery Calcium Consortium includes 59,502 asymptomatic patients age 40-75 without known CVD. Age-stratified mortality rates and parametric survival regression modeling was performed to estimate the age-specific CAC score at which CVD and cancer mortality risk were equal. ResultsThe mean age was 54±8 years (67% men) and there were 2,423 deaths over a mean 12±3 years follow-up. Among individuals with CAC = 0, cancer was the leading cause of death, with low CVD mortality rates for both younger (40-54 years) 0.2/1,000 person-years and older participants (65-75 years) 1.3/1,000 person-years. When CAC ≥400, CVD was consistently the leading cause of death among younger (71% of deaths) and older participants (56% of deaths). The CAC score at which CVD overtook cancer as the leading cause of death increased exponentially with age and was approximately 115 at age 50 and 380 at age 65. ConclusionsRegardless of age, when CAC = 0 cancer was the leading cause of death and the cardiovascular disease mortality rate was low. Our age-specific estimate for the CAC score at which CVD overtakes cancer mortality allows for a more precise approach to synergistic prediction and prevention strategies for CVD and cancer.

Reflection on modern methods: cause of death decomposition of cohort survival comparisons.

Life expectancy is most commonly measured for a period (corresponding to mortality within a given year) or for a specific birth cohort. Although widely used, period and cohort life expectancy have limitations as their time-trends often show disparities and can mask the historical mortality experience of all cohorts present at a given time. The truncated cross-sectional average length of life, or TCAL, is a period measure including all available cohort mortality information, irrespective of whether all cohort members have died. It is particularly useful for comparing cohort mortality between populations. This study extends TCAL by disentangling causes of death contributions. The strength of the approach is that it allows identification of mortality differences in cohorts with members still alive, as well as identification of which ages and causes of death contribute to mortality differentials between populations. Application of the method to Japan shows that over the period 1950-2014 a major contributor to TCAL differences with other high-longevity countries was its lower cardiovascular disease mortality.

Dietary intake of total polyphenols and the risk of all-cause and specific-cause mortality in Japanese adults: the Takayama study

PurposeSeveral epidemiological studies have demonstrated the health benefits of polyphenols, but the associations between polyphenol intake and mortality including total and major causes of death remain unclear. We investigated the associations between subjects’ total polyphenol intake and their mortality from all causes, cardiovascular disease (CVD), cancer, and other causes of death in a population-based cohort study in Japan.MethodsA total of 29,079 residents of Takayama City, Japan were analyzed. Their dietary intake was assessed using a validated semi-quantitative food-frequency questionnaire (FFQ) in 1992. Mortality was ascertained over the subsequent 16 years. The dietary polyphenol intake was calculated by matching the subjects’ food consumption data with our original polyphenol content database.ResultsA total of 5339 deaths occurred during the follow-up. After multivariable adjustment, the highest quartile of total polyphenol intake compared with the lowest quartile was significantly associated with a lower risk of all-cause mortality (HR: 0.93, 95% CI: 0.82–0.99, p trend = 0.003). The subjects in the highest quartile showed significantly lower CVD mortality compared to those in the lowest quartile, and among the types of CVD mortality, a strong inverse association was observed for stroke mortality. Inverse associations were also observed for mortality from other causes, specifically digestive disease. The total polyphenol intake was not significantly associated with the risk of cancer mortality.ConclusionsThe results of this prospective study indicate that dietary total polyphenol intake in Japanese is inversely associated with all-cause mortality and mortality from cardiovascular and digestive diseases.

Cardiorespiratory Fitness, Different Measures of Adiposity, and Cardiovascular Disease Mortality Risk in Women.

Background: Associations among cardiorespiratory fitness (CRF), different adiposity exposures, and cardiovascular disease (CVD) mortality in women are not well defined. Materials and Methods: A total of 19,838 women completed a baseline examination between 1971 and 2013. Measures included body mass index (BMI), waist circumference (WC), waist-to-height (W:HT) ratio, skinfold-derived percent body fat (% Fat), and CRF estimated from a maximal treadmill test. CRF categories were low (quintile 1), moderate (quintiles 2-3), and high (quintiles 4-5); standard cut points were used for adiposity exposures. Hazard ratios (HRs) were estimated using Cox regression. Results: During a mean follow-up period of 19.2 ± 10.3 years, 391 cardiovascular deaths occurred. HRs (95% confidence interval) for CVD in moderate and low CRF groups, using high CRF as the referent, were 1.87 (1.46-2.38) and 2.54 (1.93-3.35), respectively (p trend <0.001). HRs of obese women within each adiposity exposure were higher when compared with normal-weight women (p ≤ 0.03). Joint associations of CRF × adiposity showed a positive trend in CVD mortality across decreasing categories of CRF within each category of W:HT and % Fat, as well as within the normal and overweight BMI categories and the normal WC category (p ≤ 0.03 for each). Conclusion: Higher levels of CRF are associated with lower CVD mortality risk in women, and predict lower risk of CVD mortality in normal-weight women and in obese women. Using different measures of adiposity to predict CVD mortality risk in women may be misleading unless CRF is taken into account. These results support the American Heart Association (AHA) recommendation for including CRF as a clinical vital sign.

Total cholesterol and mortality from ischemic heart disease and overall cardiovascular disease in Korean adults.

It is not completely clear whether "the lower, the better" cholesterol hypothesis for cardiovascular disease (CVD) and ischemic heart disease (IHD) can be applied to general populations with a low risk of heart disease mortality.We prospectively followed up 503,340 Koreans who participated in routine health checkups during 2002-2003 until 2013 via linkage to national mortality records.Nonlinear associations with total cholesterol (TC) were found: U-curves for overall CVD (I00-I99; nadir at 180-200 mg/dL) and a reverse-L-curve for IHD (I20-I25). Assuming a linear association in the lower range (<200 mg/dL), TC was inversely associated with CVD mortality (HR per 39 mg/dL [1 mmol/L] increase = 0.90). In the upper range (200-349 mg/dL), TC was positively associated with CVD mortality, largely due to IHD (HR = 1.19), especially acute myocardial infarction (HR = 1.23). The associations were generally similar in men versus women and in middle-aged (40-64 years) versus elderly (≥65 years) adults.TC levels of 180-200 mg/dL were associated with the lowest CVD mortality. Below 200 mg/dL, TC had no graded positive associations with IHD mortality. It remains unclear whether the lowest cholesterol levels are associated with the least mortality from CVD and IHD in Korean adults with a low risk of heart disease.

Dietary fats and mortality among patients with type 2 diabetes: analysis in two population based cohort studies

ObjectiveTo assess the association of dietary fatty acids with cardiovascular disease mortality and total mortality among patients with type 2 diabetes.DesignProspective, longitudinal cohort study.SettingHealth professionals in the United States.Participants11 264...

2018 Guidelines for the management of dyslipidemia.

Cardiovascular disease (CVD) is becoming more prevalent worldwide and is one of the leading causes of death [1]. To lower CVD mortality, aggressive and comprehensive management of its risk factors, including dyslipidemia, hypertension, diabetes mellitus, and smoking, are crucial [2]. The incidence of coronary artery disease (CAD) is rising in South Korea and although cerebral hemorrhage has declined since 2002, cerebral infarction is on the rise [3]. This is speculated to be due to the elevated prevalence of dyslipidemia and diabetes mellitus with the growing obesity population, while hypertension is well-managed and smoking rate has reached a plateau [4]. Thus, aggressive diagnosis and treatment of dyslipidemia, the most important risk factor for atherosclerosis, are critical for lowering the incidence and mortality of CAD and cerebral infarction. To promote appropriate treatment of dyslipidemia, the Korean Society of Lipid and Atherosclerosis (KSo-LA) published the first guidelines for the management of hyperlipidemia in 1996, the second guideline in 2003, the second revision in 2009, and the third guidelines for treatment of dyslipidemia with added contents in 2015, in collaboration with 18 other relevant academic societies and organizations [5]. However, new guidelines were published in Europe in 2016 and in the United States in 2017 based on new study findings, and new drugs, such as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been launched [6-8]. Therefore, the KSoLA Treatment Guideline Committee developed the fourth guidelines for treatment and management of dyslipidemia specific to Koreans based on evidence and expert opinions on the dynamically changing treatment modalities for dyslipidemia. The fourth guideline consists of information about the epidemiology of dyslipidemia, diagnosis and treatment criteria, lifestyle interventions, drug therapy, and dyslipidemia in specific patient groups. Finally, we present currently available data and the need to develop and validate scales to assess the risk of CVD specific to Koreans and CVD biomarkers appropriate for the Korean population. The level of evidence and strength of recommendations used in the fourth guideline are shown in Table 1. The fourth guideline is available in full text and an abstract form including tables and figures in Korean. This paper is an English summary of the full text. We hope the fourth guidelines for the treatment of dyslipidemia will be useful for health professionals treating dyslipidemia. Table 1. Levels of evidence: classes of recommendation

Cardiorespiratory Fitness &amp; Healthy Vascular Aging

Healthy Vascular Aging (HVA), defined as carotid femoral pulse wave velocity (cfPWV; arterial stiffness) <7.6 m/s and absence of hypertension in adults ≥50 years of age, is associated with lower incidence of cardiovascular disease (CVD). Higher cardiorespiratory fitness (CRF) is associated with lower CVD mortality; however, the relation between HVA and CRF has not been examined. PURPOSE: To determine the relation between HVA and CRF in an apparently healthy adult population. METHODS: One hundred and one individuals (54M/47F) with a mean age of 63.5 ± 0.8 years and body mass index (BMI) of 28.3 ± 0.5 kg/m2 underwent measures of vascular hemodynamics (cfPWV; resting blood pressure, BP), CRF (VO2max), and traditional CVD risk factors. Participants were divided into either the HVA or no-HVA groups based on the resting cfPWV and BP values and medication status. Data were analyzed with unpaired t-tests and Pearson correlations. RESULTS: HVA was present in 25% (n=25) of the subjects, while 75% (n=76) had no-HVA. Compared to no-HVA, HVA were younger (59.7 ± 1.8 vs. 64.7 ± 0.9 years, p<0.05), had lower cfPWV (6.7 ± 0.1 vs. 8.5 ± 0.1 m/s, p<0.05) and systolic BP (111.2 ± 2.5 vs. 117.6 ± 1.5 mmHg, p<0.05). CRF was not different between groups (27.2 ± 1.4 vs. 25.2 ± 0.8 ml/kg/min, p>0.05), but age and sex adjusted CRF percentiles according to the Fitness Registry and Importance of Exercise National Database (FRIEND) demonstrated greater CRF in HVA vs. no-HVA (62% ± 5.7 vs. 47% ± 3.0, p<0.05). HVA compared with no-HVA had lower (p<0.05) BMI (26.3 ± 1.1 vs. 29.0 ± 0.6 kg/m2, p<0.05), waist circumference (88.9 ± 2.8 vs. 98.5 ± 1.6 cm, p<0.05), and blood glucose (91.8 ± 2.1 vs. 103.4 ± 2.6 mg/dL, p<0.05). cfPWV (r=-0.3406) and bSBP (r=-0.3202) were both inversely correlated with the FRIEND percentiles (p<0.05, both). CONCLUSIONS: Our findings indicate HVA is associated with greater CRF. These data support the notion for lower CVD-related mortality with higher levels of CRF may be attributable, in part, to HVA.

Plasma ADMA, urinary ADMA excretion, and late mortality in renal transplant recipients

Cardiovascular disease (CVD) is the leading cause of death in renal transplant recipients (RTR). Elevated plasma asymmetric dimethylarginine (pADMA), an endogenous nitric oxide synthase inhibitor produced from the turnover of methylated arginine moieties in proteins, is a risk factor for CVD and mortality. It is unknown how urinary ADMA excretion (uADMA), one of the main ADMA elimination routes, is associated with long-term survival. Furthermore, the association of pADMA and uADMA with markers for turnover of arginine-methylated proteins is unknown. We analyzed ADMA using a validated GC–MS/MS method in plasma and 24-h urine samples of 685 RTR, included ≥ 1 year after transplantation. We also analyzed urine symmetric dimethylarginine (uSDMA) using the same method. Urinary creatinine and urea excretions were used as markers for turnover of muscle protein and amino acids, respectively. We applied Cox regression analyses to study associations of pADMA, uADMA, and uSDMA with all-cause and CVD mortality. Mean pADMA was 0.61 ± 0.12 µM, uADMA was 31 ± 13 µmol/24 h, and uSDMA was 52 ± 19 µmol/24 h. Over median follow-up of 5.4 [4.9–6.1] years, 147 RTR died, of which 58 (39%) from CVD. High pADMA was associated with high all-cause mortality (HR per SD [95% CI]: 1.45 [1.26–1.67], P < 0.001), while high uADMA was associated with low all-cause and CVD mortality (HR per SD [95% CI]: 0.57 [0.47–0.69], P < 0.001, and 0.55 [0.40–0.74], P < 0.001, respectively). The associations were independent of adjustment for potential confounders. Creatinine excretion was associated with both pADMA (st. β:− 0.21, P = 0.003) and uADMA (st. β: 0.49, P < 0.001), and urea excretion was associated with uADMA (st. β: 0.56, P < 0.001). Associations of uSDMA with outcomes and with creatinine excretion and urea excretion were comparable to those of uADMA. The associations of pADMA, uADMA and uSDMA with mortality were strongly affected by adjustment for creatinine excretion and urea excretion. We found for the first time that high uADMA and high uSDMA are associated with less risk of all-cause and CVD mortality. The links of uADMA and uSDMA with markers of muscle protein and amino acid turnover may serve to further understand ADMA and SDMA homeostasis and their clinical implications.