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BACKGROUND: Dual antiplatelet therapy with a potent P2Y12 inhibitor coupled with aspirin for 1 year is the recommended treatment for patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). As an alternative, monotherapy with a P2Y12 inhibitor after a short period of dual antiplatelet therapy has emerged as a bleeding reduction strategy. METHODS: We pooled individual patient data from randomized trials that included patients with ACS undergoing PCI treated with an initial 3-month course of dual antiplatelet therapy followed by ticagrelor monotherapy versus continued ticagrelor plus aspirin. Patients sustaining a major ischemic or bleeding event in the first 3 months after PCI were excluded from analysis. The primary outcome was Bleeding Academic Research Consortium type 3 or 5 bleeding occurring between 3 and 12 months after index PCI. The key secondary end point was the composite of death, myocardial infarction, or stroke. Hazard ratios and 95% CIs were generated using Cox regression with a one-stage approach in the intention-to-treat population. RESULTS: The pooled cohort (n=7529) had a mean age of 62.8 years, 23.2% were female, and 55% presented with biomarker-positive ACS. Between 3 and 12 months, ticagrelor monotherapy significantly reduced Bleeding Academic Research Consortium 3 or 5 bleeding compared with ticagrelor plus aspirin (0.8% versus 2.1%; hazard ratio, 0.37 [95% CI, 0.24–0.56]; P <0.001). Rates of all-cause death, myocardial infarction, or stroke were not significantly different between groups (2.4% versus 2.7%; hazard ratio, 0.91 [95% CI, 0.68–1.21]; P =0.515). Findings were unchanged among patients presenting with biomarker-positive ACS. CONCLUSIONS: Among patients with ACS undergoing PCI who have completed a 3-month course of dual antiplatelet therapy, discontinuation of aspirin followed by ticagrelor monotherapy significantly reduced major bleeding without incremental ischemic risk compared with ticagrelor plus aspirin. REGISTRATION: URL: https://www.crd.york.ac.uk/prospero; Unique identifier: CRD42023449646. [ABSTRACT FROM AUTHOR]

Background and aims To evaluate the performance of the American College of Cardiology/American Heart Association (ACC/AHA) 2013 Pooled Cohort Equations in the Korean Heart Study (KHS) population and to develop a Korean Risk Prediction Model (KRPM) for atherosclerotic cardiovascular disease (ASCVD) events. Methods The KHS cohort included 200,010 Korean adults aged 40–79 years who were free from ASCVD at baseline. Discrimination, calibration, and recalibration of the ACC/AHA Equations in predicting 10-year ASCVD risk in the KHS cohort were evaluated. The KRPM was derived using Cox model coefficients, mean risk factor values, and mean incidences from the KHS cohort. Results In the discriminatory analysis, the ACC/AHA Equations' White and African–American (AA) models moderately distinguished cases from non-cases, and were similar to the KRPM: For men, the area under the receiver operating characteristic curve (AUROCs) were 0.727 (White model), 0.725 (AA model), and 0.741 (KRPM); for women, the corresponding AUROCs were 0.738, 0.739, and 0.745. Absolute 10-year ASCVD risk for men in the KHS cohort was overestimated by 56.5% (White model) and 74.1% (AA model), while the risk for women was underestimated by 27.9% (White model) and overestimated by 29.1% (AA model). Recalibration of the ACC/AHA Equations did not affect discriminatory ability but improved calibration substantially, especially in men in the White model. Of the three ASCVD risk prediction models, the KRPM showed best calibration. Conclusions The ACC/AHA Equations should not be directly applied for ASCVD risk prediction in a Korean population. The KRPM showed best predictive ability for ASCVD risk. [ABSTRACT FROM AUTHOR]

Summary 1. The inflammatory state, which is associated with the current pandemic of obesity, has been established as an important contributing pathogenic factor to the increased prevalence of the so-called metabolic syndrome. Many studies have focused on the contribution of various adipokines to this phenomenon, and in the present study, we provide an update on the emerging evidence that the pro-inflammatory factor, lipocalin-2, might influence various aspects of metabolic syndrome. 2. Previous reports indicate a positive correlation of serum lipocalin-2 with fasting glucose, the homeostasis model assessment of insulin resistance index, and the inflammatory marker high-sensitivity C-reactive protein, even after adjustment for body mass index, suggesting that it is an independent risk factor for insulin resistance, diabetes, and inflammation. Direct analysis of lipocalin-2 action now also shows effects on peripheral metabolism and on cardiovascular function. 3. A better understanding of how lipocalin-2 is regulated locally and systemically is crucial for adding to our understanding of the pathogenesis of metabolic syndrome, and to uncover potential new avenues for therapeutic approaches. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Limited information is available on the association of HDL subtypes and the risk of metabolic syndrome (MetSyn). The objective of the present study was to investigate the association of HDL subspecies with the prevalence of MetSyn in new outpatients. Methods: Five hundred forty-one new outpatients (366 males and 175 females) were enrolled in two hospitals participating in the KMSRI-Seoul Study. The new criteria for the Korean MetSyn based on the 2005 KHANES were used. Medical questionnaires, anthropometric measurements, 3-day recall dietary assessments, and blood biomarker analyses were performed. Unconditional logistic regression models were used to estimate crude and odds ratios (ORs) and 95% confidence intervals (CIs) with multivariate adjustments. The proportions of HDL subtypes were measured after subtypes were identified by 4–30% gradient gel electrophoresis. Results: Of the subjects, 50.8% were classified as MetSyn; blood pressure (BP) and fasting blood sugar (FBS) among the five criteria did not differ by gender. Increasing the HDL2b subtype significantly reduced the risk of MetSyn in males and females. The association of small size HDL3b with the risk of MetSyn was stronger in females than in males: adjusted ORs (95% CIs) for the 3rd tertile of HDL3b compared to the 1st tertile were 3.79 (CI, 2.00–7.18) in males and 11.2 (CI, 2.1–59.6) in females. However, a decreased waist circumference (WC), BP, and triglycerides (TG) were observed with increased large HDL particles in males. Conclusions: Small-sized HDL was associated with increased MetSyn risk factors and closely related to WC, BP, TG, and HOMA-IR, particularly in males. [Copyright &y& Elsevier]

Abstract: Objective: We aimed to determine the influence of apolipoprotein A5 gene (APOA5)-1131T>C single nucleotide polymorphism on the effects of dietary intervention and regular exercise (DIRE) targeting ApoA5 and triglyceride (TG) concentrations. Methods: Hypertriglyceridemia patients (TG, 150–500mg/dL, n =283) undertook a 12-week DIRE (replacing 1/3 of refined rice in their diets with legumes, increasing vegetable intake, and regular walking). Results: Pre-treatment, no genotype-related differences were detected in ApoA5, TG, or HDL cholesterol levels; however, post-treatment, subjects homozygous (T/T) for the T allele had lower serum TG (P =0.009) and higher HDL cholesterol (P =0.036) than other subjects. In T/T subjects, after adjustments for age, sex and weight changes (r1) or initial TG levels (r2), changes in ApoA5 levels negatively correlated with TG changes (r1=−0.29, P =0.05, r2=−0.28, P <0.1) and positively correlated with changes in HDL cholesterol (r1=0.30, P <0.05, r2=0.32, P <0.05) and free fatty acid (r1=0.38, P <0.01, r2=0.40, P <0.01). In those with moderate hypertriglyceridemia (TG, 200–500mg/dL, n =130), APOA5-1131T/T carriers achieved significantly lower TG (P =0.007) and higher HDL cholesterol (P <0.001) than −1131C allele carriers. Additionally, statistically significant interactions between the −1131T>C and the compliance of DIRE were found for the change in TG (P =0.002) and HDL cholesterol (P =0.039). In good compliance group, T/T subjects showed greater reduction of TG and higher increase of HDL cholesterol than other subjects. On the other hand, non-good compliance group had no significant improvement in these variables. Conclusions: APOA5-1131T/T carriers may benefit more from the DIRE than C allele carriers. These effects were remarkable in patients with moderate hypertriglyceridemia and the individuals with good compliance. [ABSTRACT FROM AUTHOR]

Abstract: The purpose of this study was to find out the effect of the ApoE genotype on the relationship between metabolic syndrome (MS) and its diagnostic components and cognitive impairment in the elderly. A total of 2944 subjects aged over 60 years were analyzed from the data of Gwangju Dementia and Mild Cognitive Impairment Study. We examined demographic characteristics, current and past illness history, drug history, Korean version-mini-mental state examination (K-MMSE). We also examined ApoE genotype and analyzed associated factors with MS. The MS was present in 53.8% of the subjects (36.8% of men and 61.1% of women). On multiple logistic regression analysis, MS was not associated with the cognitive impairment (K-MMSE score <18) adjusted for age, sex, and educational level. The interactive effect between systolic and diastolic blood pressure (SBP, and DBP, respectively) and ApoE on cognition was not significant (all p >0.3), but the interactive effect between triglyceride (TG), high-density-lipoprotein-cholesterol (HDLc) and ApoE on cognition was significant after adjustment for age, sex, and education (B =−0.285, Wald=4.194, p =0.041; B =0.372, Wald=4.134, p =0.042). These results suggest that blood TG and HDLc may affect cognitive function in the elderly in the presence of ApoE ɛ4 allele. [Copyright &y& Elsevier]

Abstract: Objective: Whereas the relation between apolipoprotein A5 (APOA5) gene polymorphisms and triglycerides (TG) levels is well established, the associations between apoA5 concentrations, TG and coronary artery disease (CAD) remain controversial. Therefore, we investigated these relations in the setting of a case–control study involving Korean males. Methods: ApoA5, TG, insulin, free fatty acid (FFA) and lipoprotein profiles were determined using a cross-sectional design in 777 healthy controls and 367 CAD patients. Results: Plasma apoA5 concentration was lower in CAD patients than controls (192.7±5.2 vs. 237.2±3.7ng/ml, P <0.001). Values in the second and top tertiles of apoA5 were associated with a decreased odds ratio (OR) for CAD when compared with values in the bottom tertile; OR for apoA5 top tertile was 0.33 (95% CI, 0.23–0.47) in the age- and BMI-adjusted model and 0.35 (95% CI, 0.23–0.56) following additional adjustments for smoking, drinking status, blood pressure, TG and HDL-cholesterol. After adjustment for age and BMI, plasma apoA5 concentration was negatively correlated with serum TG (r =−0.188, P <0.001) and insulin (r =−0.185, P <0.001) in normotriglyceridemic controls (TG<150mg/dL, n =509) whereas apoA5 was positively correlated with serum TG in hypertriglyceridemic controls (TG ≥ 150mg/dL, n =268) (r =0.246, P <0.001) and total CAD patients (r =0.177, P <0.01). Regardless of TG levels and CAD status, apoA5 concentration was positively correlated with HDL-cholesterol and FFA levels. Conclusions: Our data supports an inverse association between plasma apoA5 concentrations and CAD risk, probably due to the observed negative correlations of apoA5 with TGs and insulin, although these correlations were affected by TG levels. [Copyright &y& Elsevier]

Abstract: Background: The association between -1131T>C single nucleotide polymorphism (SNP) of the apolipoprotein A5 gene (APOA5) and hypertriglyceridemia raised the possibility that this SNP could be related to coronary artery disease (CAD) risk. Therefore, we investigated the association of this APOA5 -1131T>C SNP with circulating concentrations of APOA5, triglyceride and CAD in Koreans. Methods: CAD patients (n =741) and age-, sex-matched healthy controls (n =741) were genotyped for the APOA5 -1131T>C SNP. The main outcome measures were the odds ratio (OR) on CAD risk and lipid variables, APOA5 concentration and LDL particle size. Results: The presence of the minor allele at the -1131T>C SNP was associated with an increased risk of CAD [OR 1.34 (95% CI, 1.09–1.65), P =0.007] after adjusting for BMI, alcohol consumption, systolic blood pressure and diastolic blood pressure. There was an association between the APOA5 concentration and the -1131T>C genotype in controls (T/T: 245±7 ng/ml, T/C: 220±6, C/C: 195±12; P =0.001) and CAD patients (T/T: 218±8 ng/ml, T/C: 185±7, C/C: 169±12; P <0.001). Subjects with T/C or C/C in control and CAD patient groups showed higher triglyceride than those with T/T genotype. Also, the -1131T>C polymorphism was associated with LDL particle size (P =0.003), with the T/C or C/C controls having smaller size than the T/T controls. Conclusions: The APOA5 -1131C allele is associated with reduced APOA5 concentration and with increased CAD risk. This is consistent with the observed association between the -1131C SNP, increased triglycerides as well as small LDL particle size. [Copyright &y& Elsevier]

Objective Increased levels of inflammatory markers, such as interleukin-6 ( IL-6), are associated with type 2 diabetes (T2DM). We investigated the association of IL-6 gene polymorphisms with T2DM and circulating levels of IL-6 in Koreans. Subjects A total of 1477 subjects with normal glucose tolerance and 476 T2DM patients were included. Measurements We examined IL-6 –174G→C, –572C→G, –597G→A and –1363G→T promoter region polymorphisms. The main outcome measures were the odds ratio (OR) on T2DM risk and serum concentrations of IL-6 and high-sensitivity C-reactive protein (hs-CRP). Results Homozygosity for the rare G allele IL-6 –572C→G was associated with a higher risk of T2DM [OR 1·69 (95%CI 1·11–2·58), P = 0·015]. Serum IL-6 concentrations were associated with the IL-6 –572C→G genotype in control subjects (G/G: 2·33 ± 0·41: C/G: 1·53 ± 0·09: C/C: 1·72 ± 0·08 ng/l, P = 0·023). Also in the control group, subjects homozygous for the rare G allele showed significantly higher concentrations of hs-CRP than C/C and C/G carriers (G/G: 13·6 ± 2·9: C/G: 9·2 ± 0·6: C/C: 7·8 ± 0·4 mg/l, P = 0·003). The C-allele at the IL-6 –174 SNP was very rare (< 0·01) and –597G→A and –1363G→T were monomorphic in this population. Conclusions Our data demonstrate that the IL-6 –572G/G genotype is associated with higher serum IL-6 and hs-CRP concentrations and with increased risk for T2DM. [ABSTRACT FROM AUTHOR]

Abstract: Background: Concentrations of adiponectin, the protein product of the adipoctye C1q and collagen-domain-containing (ADIPOQ) gene are associated with type 2 diabetes and coronary artery disease. We investigate the association of single-nucleotide polymorphisms (SNPs) in the ADIPOQ gene with adiponectin concentrations, and to parameters of metabolic syndrome. Methods: 867 unrelated, non-diabetic Korean women, 20 to 69 y, were genotyped for 8 SNPs in the ADIPOQ gene (-11391G>A, -11377C>G, H241P, Y111H, G90S, R221S, 45T>G, 276G>T). Adiponectin, a homeostasis model assessment of insulin resistance (HOMA-IR), and metabolic parameters were measured. Results: Carriers of genotype T/T at position 276 had significantly higher adiponectin concentrations than G/G carriers (P=0.005). Homozygous carriers of the TG haplotype (i.e., individuals who were T/T at 45 and G/G at 276) and heterozygous carriers of the TG haplotype (TG/X) had lower adiponectin concentrations than non-TG carriers (P<0.001). Significant associations between SNP at 276 and serum concentrations of triglyceride (P=0.013), insulin (P=0.013) and HOMA-IR (P=0.012) were found. The 45-276 haplotypes had associations identical to the 276G>T SNP. In subgroup analysis, subjects carrying the TG haplotype had significantly lower adiponectin concentrations than non-TG carriers in both normal weight (P<0.001) and overweight-obese (P=0.009) subgroups. The association of the TG haplotype with increasing insulin concentrations was significant among overweight-obese subjects (P=0.004), but was not significant among normal weight subjects. A similar association was found between the 45-276 haplotype and HOMA-IR. Conclusion: There is a strong association of the adiponectin SNP276 genotypes and the adiponectin 45-276 haplotypes with circulating adiponectin concentrations in non-diabetic Korean women. In addition, this haplotype is associated with increased insulin concentrations and insulin resistance index only in overweight-obese individuals. [Copyright &y& Elsevier]

Abstract: Background: Associations between variations in the lymphotoxin-α (LTA) gene and coronary artery disease (CAD) and type 2 diabetes have previously been reported. We investigated the influence of the LTA 252A>G and 804C>A polymorphisms on circulating parameters related to metabolic syndrome in Korean patients with CAD. Methods: The study subjects comprised 446 Korean male patients with CAD (age 53.9 y, BMI 25.2 kg/m2). Results: The LTA 252A>G and 804C>A polymorphisms were almost in complete linkage disequilibrium (R 2 =99.4%). The LTA 252A>G polymorphism was associated with LDL particle size (P =0.046), HOMA-IR (P =0.022) and circulating levels of triglyceride (P =0.006), HDL-cholesterol (P =0.008), apo A1 (P =0.031), insulin (P =0.046), and adiponectin (P =0.018), after adjustment for BMI. CAD patients with LTA 252G/G (n =96) had a lower concentration of HDL-cholesterol, a smaller LDL particle size, and a higher triglyceride level, compared to those with 252A/A (n =121) or 252A/G (n =229). In addition, CAD patients with LTA 252G/G had lower concentrations of adiponectin and higher levels of insulin, and HOMA-IR than those with 252A/A. Conclusion: Homozygosity for rare alleles of the LTA 252A>G polymorphisms was associated with features of metabolic syndrome such as hyperinsulinemia, dyslipidemia, small LDL particle and low adiponectin level in CAD patients, suggesting that CAD patients with LTA 252GG are at high risk and needed an intensive intervention against further progression. [Copyright &y& Elsevier]

Abstract: We investigated whether smoking would interact with the interleukin-6 (IL-6) polymorphisms (−174G>C and −572C>G, −597G>A and −1363G>T) in determining circulating levels of inflammatory markers and its consequence to oxidative stress. The G/G genotype (n =26) of the −572C>G in nonsmokers (n =376) was associated with higher IL-6 (P =0.028), fibrinogen (P =0.007) and ox-LDL (P =0.006) than those with C/C (n =209) or C/G (n =141). Results were similar for nonsmokers and smokers (n =268), but in smokers, the −572G/G genotype was associated with a greater difference in levels of IL-6 (P =0.031), fibrinogen (P =0.001), ox-LDL (P =0.037) and PGF2α (P =0.050). IL-6 had positive relations with CRP, fibrinogen, ox-LDL and PGF2α. There was no evidence of an effect of −572C>G genotype on CRP levels in nonsmokers, however, this polymorphism was associated with a highly significant effect on CRP in smokers (P <0.001) (genotype-smoking interaction P =0.04, adjusted for age, BMI and IL-6). The C allele frequency at the −174 promoter region of IL-6 was very rare (<0.01) and −597G>A and −1363G>T were monomorphic in this study. Our results suggest that IL-6 −572C>G has a greater response over time to the inflammatory effects of smoking and this may result in smokers having higher oxidative stress in subjects with G/G compared to C/C or C/G. [Copyright &y& Elsevier]

Abstract: Background: The systemic inflammatory response is heightened in smokers. We examined whether the established cardiovascular risk factor, smoking status, might interact with the lymphotoxin-α (LTA) gene 252A>G polymorphism in determining concentrations of TNF-α and eventually IL-6, adiponectin and CRP downstream in the inflammatory cascade. Methods: We measured anthropometric parameters, serum lipid profile, glucose, TNF-α, IL-6, CRP, adiponectin and urinary excretion of 8-epi PGF2α as well as a genotyping for 252A>G polymorphism of LTA in 480 healthy Korean men. Results: After adjustment for age, 208 smokers with an average consumption of 18±1 cigarettes/d had higher concentrations of TNF-α, IL-6, CRP and urinary excretion of 8-epi PGF2α than nonsmokers (n =272). Nonsmokers with G/G had higher TNF-α and 8-epi PGF2α concentrations than those with A/A or A/G. TNF-α concentrations were higher in smokers than nonsmokers of the same genotype. Smokers with G/G showed higher TNF-α concentration than those with A/A and had higher IL-6 and urinary 8-epi PGF2α concentrations than those with A/G or A/A. Furthermore, smokers carrying the G allele showed lower adiponectin concentrations than those with A/A. There are main effects of genotype and smoking, as well as the smoking–genotype interaction to TNF-α concentration. Conclusion: Our results suggest that the LTA 252A>G polymorphism may modulate the inflammatory effects and oxidative stress of smoking. The detrimental effect of smoking is most clearly seen in men with G/G, suggesting a genotype-specific interaction with smoking. [Copyright &y& Elsevier]

Following the rapid economic development with good food supply, Koreans have changed their lifestyle and food habits. Intake trends illustrate the fall in whole grain intake with the significant rise in animal sources, edible oils and added sugar. Fat-derived energy intake increased rapidly, from about 6% in 1969 to 19% in 1998; however, average calorie intake, approximately 2000 kcal, has changed little over the same period. The 1998 survey showed that the obesity rate among adults was 1.7% for men and 3.0% for women. Although mean values of BMI has only slightly increased from 22.5 kg/m2 in 1988 to 23.3 kg/m2 in 1998, the prevalence of the high waist to hip ratio has markedly increased. Similarly, a rapid increase (140%) in mortality rates as a result of CAD was observed. This indicates that obesity is not considered to be of major clinical importance in Korea. Rather, the ability of an individual to cope with an increase in central fat distribution and dietary transition may be important in the development of CAD. Many Koreans appear to be susceptible to the development of excessive abdominal fatness even at low levels of BMI. In addition, the health consequences of visceral fat accumulation including postprandial lipemia, lipid peroxidation and negative antioxidant system appear to occur at much lower levels of BMI and are more intense than in those of European origin. The exact reasons for these ethnic variations in the development of CAD remain unclear. It is likely that genetic differences contribute to this variation in CAD risk, but different dietary and physical activity patterns may also play a role. Therefore, the major goal to prevent CAD should be the reduction of visceral fat through physical exercise and heart-healthy nutrition guidelines, including minimally refined grains and frequent consumption of vegetables and legumes, even for those subjects who are considered at low risk of CAD based on the BMI values. [Copyright &y& Elsevier]

Elevated plasma total homocysteine (hcy), a risk factor for Coronary Artery Disease (CAD), is due to defects in genes encoding for enzymes involved in hcy metabolism or from inadequate status of vitamins involved in hcy disposal. The present study was designed to examine the relationship between the genetic factors, folate and vitamin B12 status. Relationship between plasma total homocysteine, folate, vitamin B12 and genetic variation at the methylenetetrahydrofolate reductase (MTHFR) (677C→T) and methionine synthase (MS) (2756A→G) loci were measured in 149 CAD men and 230 healthy men aged 34–74 yr in Korea. There was an association of elevated plasma hcy and CAD. However, MTHFR or MS mutation were not strong determinants on the development of CAD. Our results also indicate an interaction between the MTHFR, but not MS, homozygous mutant genotype and folate and vitamin B12 status in the elevation of plasma hcy, especially in CAD men. [Copyright &y& Elsevier]

Dual antiplatelet therapy (DAPT) for 12 months is the standard of care after coronary stenting in patients with acute coronary syndrome (ACS). The aim of this individual patient-level meta-analysis was to summarise the evidence comparing DAPT de-escalation to ticagrelor monotherapy versus continuing DAPT for 12 months after coronary drug-eluting stent implantation. A systematic review and individual patient data (IPD)-level meta-analysis of randomised trials with centrally adjudicated endpoints was performed to evaluate the comparative efficacy and safety of ticagrelor monotherapy (90 mg twice a day) after short-term DAPT (from 2 weeks to 3 months) versus 12-month DAPT in patients undergoing percutaneous coronary intervention with a coronary drug-eluting stent. Randomised trials comparing P2Y 12 inhibitor monotherapy with DAPT after coronary revascularisation were searched in Ovid MEDLINE, Embase, and two websites (www.tctmd.com and www.escardio.org) from database inception up to May 20, 2024. Trials that included patients with an indication for long-term oral anticoagulants were excluded. The risk of bias was assessed using the revised Cochrane risk-of-bias tool. The principal investigators of the eligible trials provided IPD by means of an anonymised electronic dataset. The three ranked coprimary endpoints were major adverse cardiovascular or cerebrovascular events (MACCE; a composite of all-cause death, myocardial infarction, or stroke) tested for non-inferiority in the per-protocol population; and Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding and all-cause death tested for superiority in the intention-to-treat population. All outcomes are reported as Kaplan–Meier estimates. The non-inferiority was tested using a one-sided α of 0·025 with the prespecified non-inferiority margin of 1·15 (hazard ratio [HR] scale), followed by the ranked superiority testing at a two-sided α of 0·05. This study is registered with PROSPERO (CRD42024506083). A total of 8361 unique citations were screened, of which 610 records were considered potentially eligible during the screening of titles and abstracts. Of these, six trials that randomly assigned patients to ticagrelor monotherapy or DAPT were identified. De-escalation took place a median of 78 days (IQR 31–92) after intervention, with a median duration of treatment of 334 days (329−365). Among 23 256 patients in the per-protocol population, MACCE occurred in 297 (Kaplan–Meier estimate 2·8%) with ticagrelor monotherapy and 332 (Kaplan–Meier estimate 3·2%) with DAPT (HR 0·91 [95% CI 0·78–1·07]; p=0·0039 for non-inferiority; τ2<0·0001). Among 24 407 patients in the intention-to-treat population, the risks of BARC 3 or 5 bleeding (Kaplan–Meier estimate 0·9% vs 2·1%; HR 0·43 [95% CI 0·34–0·54]; p<0·0001 for superiority; τ2=0·079) and all-cause death (Kaplan–Meier estimate 0·9% vs 1·2%; 0·76 [0·59–0·98]; p=0·034 for superiority; τ2<0·0001) were lower with ticagrelor monotherapy. Trial sequential analysis showed strong evidence of non-inferiority for MACCE and superiority for bleeding among the overall and ACS populations (the z-curve crossed the monitoring boundaries or the required information size without crossing the futility boundaries or approaching the null). The treatment effects were heterogeneous by sex for MACCE (p interaction=0·041) and all-cause death (p interaction=0·050), indicating a possible benefit in women with ticagrelor monotherapy, and by clinical presentation for bleeding (p interaction=0·022), indicating a benefit in ACS with ticagrelor monotherapy. Our study found robust evidence that, compared with 12 months of DAPT, de-escalation to ticagrelor monotherapy does not increase ischaemic risk and reduces the risk of major bleeding, especially in patients with ACS. Ticagrelor monotherapy might also be associated with a mortality benefit, particularly among women, which warrants further investigation. Cardiocentro Ticino Institute, Ente Ospedaliero Cantonale. [ABSTRACT FROM AUTHOR]

Background: The impact of rosuvastatin versus atorvastatin on new-onset diabetes mellitus (NODM) among patients treated with high-intensity statin therapy for coronary artery disease (CAD) remains to be clarified. This study aimed to evaluate the risk of NODM in patients with CAD treated with rosuvastatin compared to atorvastatin in the randomized LODESTAR trial. Methods: In the LODESTAR trial, patients with CAD were randomly assigned to receive either rosuvastatin or atorvastatin using a 2-by-2 factorial randomization. In this post-hoc analysis, the 3-year incidence of NODM was compared between rosuvastatin and atorvastatin treatment in the as-treated population with high-intensity statin therapy as the principal population of interest. Results: Among 2932 patients without diabetes mellitus at baseline, 2377 were included in the as-treated population analysis. In the as-treated population with high-intensity statin therapy, the incidence of NODM was not significantly different between the rosuvastatin and atorvastatin groups (11.4% [106/948] versus 8.8% [73/856], hazard ratio [HR] = 1.32, 95% confidence interval [CI] = 0.98 to 1.77, P = 0.071). When the risk of NODM with rosuvastatin versus atorvastatin was assessed according to the achieved low-density lipoprotein cholesterol (LDL-C) level, the risk of NODM began to increase at a LDL-C level below 70 mg/dL. The incidence of NODM was significantly greater in the rosuvastatin group than it was in the atorvastatin group when the achieved LDL-C level was < 70 mg/dL (13.9% versus 8.0%; HR = 1.79, 95% CI 1.18 to 2.73, P = 0.007). Conclusions: Among CAD patients receiving high-intensity statin therapy, the incidence of NODM was not significantly different between rosuvastatin and atorvastatin. However, a drug effect of the statin type on NODM was observed when the achieved LDL-C level was < 70 mg/dL. Trial registration: ClinicalTrials.gov, Identifier: NCT02579499. [ABSTRACT FROM AUTHOR]

Background The optimal statin treatment strategy that is balanced for both efficacy and safety has not been clearly determined in older adults with coronary artery disease (CAD). Methods In the post hoc analysis of the LODESTAR (low-density lipoprotein cholesterol-targeting statin therapy versus intensity-based statin therapy in patients with coronary artery disease) trial, the impact between a treat-to-target strategy versus a high-intensity statin therapy strategy was compared in older adults (aged 75 years or older). The goal of treat-to-target low-density lipoprotein cholesterol (LDL-C) level was 50–70 mg/dl. The primary endpoint comprised the three-year composite of all-cause death, myocardial infarction, stroke or coronary revascularisation. Results Among 4,400 patients with CAD enrolled in the LODESTAR trial, 822 (18.7%) were aged 75 years or older. Poor clinical outcomes and risk factors for atherosclerosis were more frequently observed in older adults than in younger population (<75 years old). Among these older adults with CAD, the prescription rate of high-intensity statin was significantly lower in the treat-to-target strategy group throughout the study period (P  < 0.001). The mean LDL-C level for three years was 65 ± 16 mg/dl in the treat-to-target strategy group and 64 ± 18 mg/dl in the high-intensity statin group (P  = 0.34). The incidence of primary endpoint occurrence was 10.9% in the treat-to-target strategy group and 12.0% in the high-intensity statin group (hazard ratio 0.92, 95% confidence interval 0.61–1.38, P  = 0.69). Conclusions High-intensity statin therapy is theoretically more necessary in older adults because of worse clinical outcomes and greater number of risk factors for atherosclerosis. However, the primary endpoint occurrence with a treat-to-target strategy with an LDL-C goal of 50–70 mg/dl was comparable to that of high-intensity statin therapy and reduced utilisation of a high-intensity statin. Taking efficacy as well as safety into account, adopting a tailored approach may be considered for this high-risk population. Trial Registration ClinicalTrials.gov , NCT02579499. [ABSTRACT FROM AUTHOR]

The benefits of intravascular ultrasonography (IVUS)-guided percutaneous coronary intervention (PCI) in the clinical context of cardiogenic shock (CS) complicating acute myocardial infarction are lacking. We aimed to investigate the impact of IVUS-guided PCI in patients with AMI and CS. From the pooled data based on a series of Korean AMI registries during 2011–2020, we identified 1418 consecutive patients who underwent PCI with second generation drug-eluting stent (DES) for AMI and CS. The primary endpoint was the 1-year rate of target lesion failure (TLF), defined as the composite of cardiac death, target vessel myocardial infarction, and ischemic-driven target lesion revascularization. In total, 294 (20.7%) and 1124 (79.3%) underwent IVUS-guided and angiography-guided PCI with second generation DES implantation, respectively. The 1-year TLF was not significantly different between groups after IPTW analysis (hazard ratio 0.93, 95% confidence interval 0.65–1.34, p = 0.70). Additionally, the adjusted landmark analysis for TLF at 30 days and between 30 days and 1 year after PCI demonstrated no significant difference between the groups. In conclusion, in patients with AMI and CS who underwent PCI with second-generation DES, IVUS-guided PCI did not improve the 1-year TLF compared with angiography-guided PCI. Registration: URL: http://cris.nih.go.kr. KCT0000863 and KCT0008355. [ABSTRACT FROM AUTHOR]

Aim: This study evaluated the safety and efficacy of a moderate‐intensity statin with ezetimibe combination therapy versus high‐intensity statin monotherapy in patients with metabolic syndrome (MetS) and atherosclerotic cardiovascular disease. Materials and Methods: In this post‐hoc subgroup analysis of the RACING trial, patients were analysed based on the presence of MetS. MetS was defined as meeting at least three of the five following criteria: (a) elevated waist circumference; (b) elevated triglycerides; (c) reduced high‐density lipoprotein cholesterol; (d) elevated blood pressure; and (e) elevated fasting glucose. The primary outcome was a 3‐year composite of cardiovascular death, major cardiovascular events, or non‐fatal stroke. Results: Of the 3780 patients enrolled in the RACING trial, 1703 (45.1%) had MetS at baseline. The primary outcome rate was 10.1% and 10.3% in patients with MetS receiving ezetimibe combination therapy versus high‐intensity statin monotherapy (hazard ratio = 0.97; 95% confidence interval = 0.72‐1.32; p =.868). Lower rates of intolerance‐related drug discontinuation or dose reduction (3.9% vs. 8.0%; p <.001) and lower low‐density lipoprotein cholesterol levels (57 vs. 65 mg/dl; p <.001) were observed with ezetimibe combination therapy versus high‐intensity statin monotherapy. Furthermore, the rate of new‐onset diabetes was 18.5% and 19.1% in each group (p =.822). There were no significant interactions between MetS and therapy regarding study outcomes in the total population. Conclusions: In patients with MetS and atherosclerotic cardiovascular disease, a moderate‐intensity statin with ezetimibe combination therapy had comparable cardiovascular benefits with those of high‐intensity statin monotherapy. Meanwhile, ezetimibe combination therapy was associated with lower drug intolerance and low‐density lipoprotein cholesterol levels, but there was no apparent between‐group difference in new‐onset diabetes. [ABSTRACT FROM AUTHOR]

BACKGROUND: Stopping aspirin within 1 month after implantation of a drug-eluting stent for ticagrelor monotherapy has not been exclusively evaluated for patients with acute coronary syndrome. The aim of this study was to investigate whether ticagrelor monotherapy after <1 month of dual antiplatelet therapy (DAPT) is noninferior to 12 months of ticagrelor-based DAPT for adverse cardiovascular and bleeding events in patients with acute coronary syndrome. METHODS: In this randomized, open-label, noninferiority trial, 2850 patients with acute coronary syndrome who underwent drug-eluting stent implantation at 24 centers in South Korea were randomly assigned (1:1) to receive either ticagrelor monotherapy (90 mg twice daily) after <1 month of DAPT (n=1426) or 12 months of ticagrelor-based DAPT (n=1424) between April 24, 2019, and May 31, 2022. The primary end point was the net clinical benefit as a composite of all-cause death, myocardial infarction, definite or probable stent thrombosis, stroke, and major bleeding at 1 year after the index procedure in the intention-to-treat population. Key secondary end points were the individual components of the primary end point. RESULTS: Among 2850 patients who were randomized (mean age, 61 years; 40% ST-segment–elevation myocardial infarction), 2823 (99.0%) completed the trial. Aspirin was discontinued at a median of 16 days (interquartile range, 12–25 days) in the group receiving ticagrelor monotherapy after <1 month of DAPT. The primary end point occurred in 40 patients (2.8%) in the group receiving ticagrelor monotherapy after <1-month DAPT, and in 73 patients (5.2%) in the ticagrelor-based 12-month DAPT group (hazard ratio, 0.54 [95% CI, 0.37–0.80]; P <0.001 for noninferiority; P =0.002 for superiority). This finding was consistent in the per-protocol population as a sensitivity analysis. The occurrence of major bleeding was significantly lower in the ticagrelor monotherapy after <1-month DAPT group compared with the 12-month DAPT group (1.2% versus 3.4%; hazard ratio, 0.35 [95% CI, 0.20–0.61]; P <0.001). CONCLUSIONS: This study provides evidence that stopping aspirin within 1 month for ticagrelor monotherapy is both noninferior and superior to 12-month DAPT for the 1-year composite outcome of death, myocardial infarction, stent thrombosis, stroke, and major bleeding, primarily because of a significant reduction in major bleeding, among patients with acute coronary syndrome receiving drug-eluting stent implantation. Low event rates, which may suggest enrollment of relatively non–high-risk patients, should be considered in interpreting the trial. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03797651. [ABSTRACT FROM AUTHOR]

Introduction: A sufficient oxygen supply to ischemic limb tissue is the most important requirement for wound healing and limb salvage. We investigated whether partial venous occlusion in the common iliac vein (CIV) causes a further increase of venous oxygenation in a porcine model of acute hindlimb ischemia. Materials and methods: In 7 pigs, the model of acute hindlimb ischemia was created with intra-vascular embolization of the common iliac artery (CIA). The arterial and venous oxygen saturation was evaluated at different moments. Oxygen saturation was evaluated at baseline (T0), just after the arterial embolization (T1), at 10 minutes (T2), at 20 minutes (T3), and at 40 minutes (T4). Next, an intentional partial venous occlusion was achieved by inflating the vascular balloon at the level of the right CIV. Then, blood sampling was repeated at 5 minutes (T5), at 15 minutes (T6), and at 25 minutes (T7). Results: The arterial oxygen saturation in the right SFA was similar during all phases. In contrast, after arterial embolization, an immediate reduction of venous oxygen saturation was observed (from 85.57 ± 1.72 at T0 to 71.86 ± 7.58 at T4). After the partial venous occlusion, interestingly, the venous oxygen saturations (T5-T7) were significantly increased, again. The venous oxygen saturations evaluated in the hindlimb ischemia with partial venous occlusion and in the control limb (without partial venous occlusion) were significantly over time. Venous oxygen saturations in the experimental limbs were higher than those in the control limbs (79.28 ± 4.82 vs 59.00 ± 2.82, p-value <0.001, 79.71 ± 4.78 vs 60.00 ± 4.24 at T7, p-value <0.001). Conclusions: Partial venous occlusion results in an increase of venous oxygen saturation in the ischemic limb, while significant changes in venous oxygen saturation are not observed in the control limb. An explanation for this may be that the oxygen consumption in the limb tissue is increased because it gets congested with the partial venous occlusion in the right CIV. [ABSTRACT FROM AUTHOR]

We aimed to evaluate sex differences in the effects of moderate-intensity statin with ezetimibe combination therapy (rosuvastatin 10 mg plus ezetimibe) versus high-intensity statin (rosuvastatin 20 mg) monotherapy in patients with atherosclerotic cardiovascular disease (ASCVD). This was a sex-specific subgroup analysis of the RACING trial that evaluated the interaction between sex and treatment strategies for the primary outcome (composite of cardiovascular death, major cardiovascular events, or nonfatal stroke at 3 years). Of 3780 patients in the RACING trial, 954 (25.2%) were women. Regardless of sex, the effect of moderate-intensity statin with ezetimibe combination therapy on primary outcome compared with high-intensity statin monotherapy was similar (hazard ratio [HR] 0.98 [0.63–1.52] in women; HR 0.90 [0.71–1.14] in men). The rate of discontinuation or dose reduction of study drugs due to intolerance was lower in the ezetimibe combination group than in the high-intensity statin monotherapy group in both women (4.5% vs. 8.6%, P = 0.014) and men (4.8% vs. 8.0%, P < 0.001). LDL cholesterol levels of < 70 mg/dL at 1, 2, and 3 years were more frequently achieved in the ezetimibe combination group than in the high-intensity statin monotherapy group (all P < 0.001) in both sexes. There were no significant interactions between sex and treatment groups regarding the primary outcome, discontinuation, or dose reduction of study drugs, or the proportion of achievement of LDL cholesterol levels < 70 mg/dL. The effect of ezetimibe combination therapy for the 3-year composite outcomes was not different in both men and women. The benefits of ezetimibe combination therapy on LDL cholesterol lowering and drug tolerance were similarly observed regardless of sex. Trial registration: https://clinicaltrials.gov; Unique identifier: NCT03044665. [ABSTRACT FROM AUTHOR]

The routine use of high-intensity statins should be considered carefully in elderly patients because of their higher risk of intolerance or adverse events. We evaluated the impact of moderate-intensity statin with ezetimibe combination therapy compared with high-intensity statin monotherapy in elderly patients with atherosclerotic cardiovascular disease (ASCVD). In this post hoc analysis of the RACING (RAndomized Comparison of Efficacy and Safety of Lipid-lowerING With Statin Monotherapy Versus Statin/Ezetimibe Combination for High-risk Cardiovascular Diseases) trial, patients were stratified by age (≥75 years and <75 years). The primary endpoint was a 3-year composite of cardiovascular death, major cardiovascular events, or nonfatal stroke. Among the 3,780 enrolled patients, 574 (15.2%) were aged ≥75 years. The rates of the primary endpoint were not different between the moderate-intensity statin with ezetimibe combination therapy group and the high-intensity statin monotherapy group among patients aged ≥75 years (10.6% vs 12.3%; HR: 0.87; 95% CI: 0.54-1.42; P = 0.581) and those <75 years (8.8% vs 9.4%; HR: 0.94; 95% CI: 0.74-1.18; P = 0.570) (P for interaction = 0.797). Moderate-intensity statin with ezetimibe combination therapy was associated with lower rates of intolerance-related drug discontinuation or dose reduction among patients aged ≥75 years (2.3% vs 7.2%; P = 0.010) and those <75 years (5.2% vs 8.4%; P < 0.001) (P for interaction = 0.159). Moderate-intensity statin with ezetimibe combination therapy showed similar cardiovascular benefits to those of high-intensity statin monotherapy with lower intolerance-related drug discontinuation or dose reduction in elderly patients with ASCVD having a higher risk of intolerance, nonadherence, and discontinuation with high-intensity statin therapy. (RAndomized Comparison of Efficacy and Safety of Lipid-lowerING With Statin Monotherapy Versus Statin/Ezetimibe Combination for High-risk Cardiovascular Diseases [RACING Trial]; NCT03044665) [Display omitted] [ABSTRACT FROM AUTHOR]

Key Points: Question: Is treatment to a goal low-density lipoprotein cholesterol (LDL-C) level between 50 and 70 mg/dL noninferior to a strategy using high-intensity statin therapy among patients with coronary artery disease? Findings: In this randomized noninferiority trial that included 4400 patients with coronary artery disease, the rate of the 3-year composite of all-cause death, myocardial infarction, stroke, or any coronary revascularization was 8.1% in the treat-to-target strategy group compared with 8.7% in the high-intensity statin therapy group, a difference that met the prespecified noninferiority margin of 3.0 percentage points. Meaning: Among patients with coronary artery disease, the treat-to-target LDL-C strategy was noninferior to the high-intensity statin strategy for major clinical outcomes. Importance: In patients with coronary artery disease, some guidelines recommend initial statin treatment with high-intensity statins to achieve at least a 50% reduction in low-density lipoprotein cholesterol (LDL-C). An alternative approach is to begin with moderate-intensity statins and titrate to a specific LDL-C goal. These alternatives have not been compared head-to-head in a clinical trial involving patients with known coronary artery disease. Objective: To assess whether a treat-to-target strategy is noninferior to a strategy of high-intensity statins for long-term clinical outcomes in patients with coronary artery disease. Design, Setting, and Participants: A randomized, multicenter, noninferiority trial in patients with a coronary disease diagnosis treated at 12 centers in South Korea (enrollment: September 9, 2016, through November 27, 2019; final follow-up: October 26, 2022). Interventions: Patients were randomly assigned to receive either the LDL-C target strategy, with an LDL-C level between 50 and 70 mg/dL as the target, or high-intensity statin treatment, which consisted of rosuvastatin, 20 mg, or atorvastatin, 40 mg. Main Outcomes and Measures: Primary end point was a 3-year composite of death, myocardial infarction, stroke, or coronary revascularization with a noninferiority margin of 3.0 percentage points. Results: Among 4400 patients, 4341 patients (98.7%) completed the trial (mean [SD] age, 65.1 [9.9] years; 1228 females [27.9%]). In the treat-to-target group (n = 2200), which had 6449 person-years of follow-up, moderate-intensity and high-intensity dosing were used in 43% and 54%, respectively. The mean (SD) LDL-C level for 3 years was 69.1 (17.8) mg/dL in the treat-to-target group and 68.4 (20.1) mg/dL in the high-intensity statin group (n = 2200) (P =.21, compared with the treat-to-target group). The primary end point occurred in 177 patients (8.1%) in the treat-to-target group and 190 patients (8.7%) in the high-intensity statin group (absolute difference, –0.6 percentage points [upper boundary of the 1-sided 97.5% CI, 1.1 percentage points]; P <.001 for noninferiority). Conclusions and Relevance: Among patients with coronary artery disease, a treat-to-target LDL-C strategy of 50 to 70 mg/dL as the goal was noninferior to a high-intensity statin therapy for the 3-year composite of death, myocardial infarction, stroke, or coronary revascularization. These findings provide additional evidence supporting the suitability of a treat-to-target strategy that may allow a tailored approach with consideration for individual variability in drug response to statin therapy. Trial Registration: ClinicalTrials.gov Identifier: NCT02579499 This randomized clinical trial compares the efficacy of a treat-to-target low-density lipoprotein cholesterol (LDL-C) strategy of 50 to 70 mg/dL as the goal vs high-intensity statin therapy for the 3-year composite of death, myocardial infarction, stroke, or coronary revascularization in patients with coronary artery disease. [ABSTRACT FROM AUTHOR]

Regarding stent expansion indices, previous optical coherence tomography (OCT) studies have shown minimal stent area (MSA) to be most predictive of adverse events. We sought to evaluate the impact of various stent expansion and apposition indices by post-stent OCT on clinical outcomes and find OCT-defined optimal stent implantation criteria. A total of 1071 patients with 1123 native coronary artery lesions treated with new-generation drug-eluting stents with OCT guidance and final post-stent OCT analysis were included. Several stent expansion indices (MSA, MSA/average reference lumen area, MSA/distal reference lumen area, mean stent expansion, and stent expansion by linear model [stent volume/adaptive reference lumen volume]) were evaluated for their association with device-oriented clinical endpoints (DoCE) including cardiac death, target vessel-related myocardial infarction (MI) or stent thrombosis, and target lesion revascularization. MSA was negatively correlated with the risk of DoCE (hazard ratio [HR] 0.80 [0.68‒0.94]). However, stent expansion by linear model representing the overall volumetric stent expansion was associated with greater risk of DoCE (HR 1.02 [1.00‒1.04]). As categorical criteria, MSA < 5.0 mm2 (HR 3.90 [1.99‒7.65]), MSA/distal reference lumen area < 90% (HR 2.16 [1.12‒4.19]), and stent expansion by linear model ≥ 65.0% (HR 1.95 [1.03‒3.89]) were independently associated with DoCE. This OCT study highlights the importance of sufficient stent expansion to achieve adequate, absolute, and relative MSA criteria for improving clinical outcome. It also emphasises that overall volumetric excessive stent expansion may have detrimental effects. [ABSTRACT FROM AUTHOR]

The effects of hypertension on long-term outcomes according to glycemic status in patients with acute myocardial infarction (AMI) after successful implantation of newer-generation drug-eluting stents (DES) have not been fully investigated. In this retrospective cohort study, a total of 11,911 patients were classified into 6 groups according to their glycemic status and presence or absence of hypertension. The major outcome was major adverse cardiac events (MACE), defined as all-cause death, recurrent myocardial infarction (Re-MI), or any revascularization. In patients without hypertension, the major outcomes were similar between the normoglycemia and prediabetes groups. However, MACE, all-cause death, cardiac death (CD), Re-MI rates were higher in patients with type 2 diabetes mellitus (T2DM) than in normoglycemic patients. Additionally, Re-MI was higher in patients with T2DM than in prediabetic patients. In patients with hypertension, although the major outcomes were similar between the prediabetes and T2DM groups, in both the prediabetes and T2DM groups, MACE, all-cause death, and CD rates were higher than those in the normoglycemia group. During a 2-year follow-up, the comparable harmful effects of hypertension in patients with AMI and prediabetes or T2DM were observed. Effective blood pressure and glucose control should be strengthened to reduce mortality in these patients. [ABSTRACT FROM AUTHOR]

It remains unclear whether P2Y 12 inhibitor monotherapy preserves ischemic protection while limiting bleeding risk compared with dual antiplatelet therapy (DAPT) after complex percutaneous coronary intervention (PCI). We sought to assess the effects of P2Y 12 inhibitor monotherapy after 1-month to 3-month DAPT vs standard DAPT in relation to PCI complexity. We pooled patient-level data from randomized controlled trials comparing P2Y 12 inhibitor monotherapy and standard DAPT on centrally adjudicated outcomes after coronary revascularization. Complex PCI was defined as any of 6 criteria: 3 vessels treated, ≥3 stents implanted, ≥3 lesions treated, bifurcation with 2 stents implanted, total stent length >60 mm, or chronic total occlusion. The primary efficacy endpoint was all-cause mortality, myocardial infarction, and stroke. The key safety endpoint was Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding. Of 22,941 patients undergoing PCI from 5 trials, 4,685 (20.4%) with complex PCI had higher rates of ischemic events. The primary efficacy endpoint was similar between P2Y 12 inhibitor monotherapy and DAPT among patients with complex PCI (HR: 0.87; 95% CI: 0.64-1.19) and noncomplex PCI (HR: 0.91; 95% CI: 0.76-1.09; P interaction = 0.770). The treatment effect was consistent across all the components of the complex PCI definition. Compared with DAPT, P2Y 12 inhibitor monotherapy consistently reduced BARC 3 or 5 bleeding in complex PCI (HR: 0.51; 95% CI: 0.31-0.84) and noncomplex PCI patients (HR: 0.49; 95% CI: 0.37-0.64; P interaction = 0.920). P2Y 12 inhibitor monotherapy after 1-month to 3-month DAPT was associated with similar rates of fatal and ischemic events and lower risk of major bleeding compared with standard DAPT, irrespective of PCI complexity. (PROSPERO [P2Y12 Inhibitor Monotherapy Versus Standard Dual Antiplatelet Therapy After Coronary Revascularization: Individual Patient Data Meta-Analysis of Randomized Trials]; CRD42020176853) [Display omitted] [ABSTRACT FROM AUTHOR]

Previous studies have not compared outcomes between different percutaneous coronary intervention (PCI) strategies and lesion locations in non-left main (LM) bifurcation lesions. We enrolled 2044 patients from a multicenter registry with an LAD bifurcation lesion (n = 1551) or non-LAD bifurcation lesion (n = 493). The primary outcome was target lesion failure (TLF), a composite of cardiac death, myocardial infarction, and target lesion revascularization (TLR). During a median follow-up period of 38 months, non-LAD bifurcation lesions treated with the two-stent strategy, compared with the one-stent strategy, were associated with more frequent TLF (20.7% vs. 6.3%, p < 0.01), TLR (16.7% vs. 4.7%, p < 0.01), and target vessel revascularization (TVR; 18.2% vs. 6.3%, p < 0.01). There was no significant difference in outcome among LAD bifurcation lesions treated with different PCI strategies. The two-stent strategy was associated with a higher risk of TLF (adjusted HR 4.34, CI 1.93–9.76, p < 0.01), TLR (adjusted HR 4.30, CI 1.64–11.27, p < 0.01), and TVR (adjusted HR 5.07, CI 1.69–9.74, p < 0.01) in the non-LAD bifurcation lesions. The planned one-stent strategy is preferable to the two-stent strategy for the treatment of non-LAD bifurcation lesions. [ABSTRACT FROM AUTHOR]

Functional assessment using fractional flow reserve (FFR) and anatomical assessment using optical coherence tomography (OCT) are used in clinical practice for patients with intermediate coronary stenosis. Moreover, coronary computed tomography angiography (CTA) is a common noninvasive imaging technique for evaluating suspected coronary artery disease before being referred for angiography. This study aimed to investigate the association between FFR and plaque characteristics assessed using coronary CTA and OCT for intermediate coronary stenosis. Based on a prospective multicenter registry, 159 patients having 339 coronary lesions with intermediate stenosis were included. All patients underwent coronary CTA before being referred for coronary angiography, and both FFR measurements and OCT examinations were performed during angiography. A stenotic lesion identified with FFR ≤0.80 was deemed diagnostic of an ischemia-causing lesion. The predictive value of plaque characteristics assessed using coronary CTA and OCT for identifying lesions causing ischemia was analyzed. Stenosis severity and plaque characteristics on coronary CTA and OCT differed between lesions that caused ischemia and those that did not. In multivariate analysis, low attenuation plaque on coronary CTA (odds ratio [OR]=2.78; P =0.038), thrombus (OR=5.13; P =0.042), plaque rupture (OR=3.25; P =0.017), and intimal vasculature on OCT (OR=2.57; P =0.012) were independent predictors of ischemic lesions. Increasing the number of these plaque characteristics offered incremental improvement in predicting the lesions causing ischemia. Comprehensive anatomical evaluation of coronary stenosis may provide additional supportive information for predicting the lesions causing ischemia. Prediction of lesions causing ischemia by plaque characteristics on coronary computed tomography angiography and optical coherence tomography. Based on a prospective multicenter registry, this study evaluated the association between the FFR and plaque characteristics assessed using coronary CTA and OCT in patients with intermediate coronary stenosis. In addition to stenosis severity on coronary CTA and OCT, plaque characteristics, including low attenuation plaque on coronary CTA and thrombus, plaque rupture, and intimal vasculature on OCT, were independent predictors for the lesions causing ischemia (FFR ≤0.80). CI, confidence interval; CTA, coronary computed tomography; FFR, fractional flow reserve; OCT, optical coherence tomography; OR, odds ratio. [Display omitted] • Plaque characteristics on coronary CTA and OCT were closely related with FFR-based functional assessment of coronary stenosis. • Low attenuation plaque on coronary CTA was independent predictor of ischemic lesions. • Thrombus, plaque rupture, and intimal vasculature on OCT were also independent predictors of ischemic lesions. • Comprehensive anatomical evaluation of coronary stenosis aids in predicting lesions causing ischemia. [ABSTRACT FROM AUTHOR]

Background: Drug combinations rather than increasing doses of one drug can achieve greater efficacy and lower risks. Thus, as an alternative to high-intensity statin monotherapy, moderate-intensity statin with ezetimibe combination therapy can lower LDL cholesterol concentrations effectively while reducing adverse effects. However, evidence from randomised trials to compare long-term clinical outcomes is needed.Methods: In this randomised, open-label, non-inferiority trial, patients with atherosclerotic cardiovascular disease (ASCVD) at 26 clinical centres in South Korea were randomly assigned (1:1) to receive either moderate-intensity statin with ezetimibe combination therapy (rosuvastatin 10 mg with ezetimibe 10 mg) or high-intensity statin monotherapy (rosuvastatin 20 mg). The primary endpoint was the 3-year composite of cardiovascular death, major cardiovascular events, or non-fatal stroke, in the intention-to-treat population with a non-inferiority margin of 2·0%. This trial is registered with ClinicalTrials.gov, NCT03044665 and is complete.Findings: Between Feb 14, 2017, and Dec 18, 2018, 3780 patients were enrolled: 1894 patients to the combination therapy group and 1886 to the high-intensity statin monotherapy group. The primary endpoint occurred in 172 patients (9·1%) in the combination therapy group and 186 patients (9·9%) in the high-intensity statin monotherapy group (absolute difference -0·78%; 90% CI -2·39 to 0·83). LDL cholesterol concentrations of less than 70 mg/dL at 1, 2, and 3 years were observed in 73%, 75%, and 72% of patients in the combination therapy group, and 55%, 60%, and 58% of patients in the high-intensity statin monotherapy group (all p<0·0001). Discontinuation or dose reduction of the study drug by intolerance was observed in 88 patients (4·8%) and 150 patients (8·2%), respectively (p<0·0001).Interpretation: Among patients with ASCVD, moderate-intensity statin with ezetimibe combination therapy was non-inferior to high-intensity statin monotherapy for the 3-year composite outcomes with a higher proportion of patients with LDL cholesterol concentrations of less than 70 mg/dL and lower intolerance-related drug discontinuation or dose reduction.Funding: Hanmi Pharmaceutical. [ABSTRACT FROM AUTHOR]

The optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) with drug-eluting stent in patients with chronic kidney disease (CKD) is not clearly established. This study purposed to compare clinical outcomes of patients with 6–12 (standard) versus 12–24 months (prolonged) DAPT according to CKD. Using a nationwide, claim-based database, we retrospectively evaluated association between DAPT duration and clinical outcomes including death, composite ischemic event, and composite bleeding event between 1 and 3 years after PCI. CKD was defined as estimated glomerular filtration rate <60 mL/min/1.73 m2. Of 73,941 eligible patients, 13,425 (18.2%) had CKD and 49,019 (66%) were prescribed prolonged DAPT. Prolonged DAPT had no significant impact on the risk of clinical outcomes in patients with normal renal function. In patients with CKD, prolonged DAPT was associated with a lower risk of all-cause death (HR 0.85, 95% CI 0.76–0.95) and composite ischemic events (HR 0.87, 95% CI 0.78–0.96) and a higher risk of composite bleeding events (HR 1.18, 95% CI 1.02–1.37). Benefit of prolonged DAPT on reducing composite ischemic event increased significantly in patients with worsened renal dysfunction (p interaction = 0.02) while there was no significant interaction between its bleeding risk and renal dysfunction (p interaction = 0.22). While standard DAPT would be recommended in patients with normal renal function, tailored decision for DAPT duration would be considered in those with CKD to balance between ischemic and bleeding risks. [Display omitted] • Chronic kidney disease (CKD) has been known to increase both bleeding and ischemic risks after percutaneous coronary intervention (PCI). • Of 73,941 patients, prolonged dual antiplatelet therapy (DAPT) led to less all-cause death and composite ischemic events but more composite bleeding events in patients with CKD. • Our findings support the need for careful considerations of DAPT duration based on ischemic-bleeding risk balance in patients with CKD after PCI. [ABSTRACT FROM AUTHOR]

Arterial calcification (AC), which is an important process in the pathogenesis of atherosclerosis, is accelerated by angiotensin II (Ang II), a critical effector of the renin-angiotensin system (RAS). Receptor for advanced glycation end-product (RAGE) is an important pattern recognition receptor downstream of Ang II. Although recent studies have suggested an association between RAGE-mediated signaling and RAS in AC, the detailed mechanism, particularly in relation to Ang II, remains unclear. Therefore, we investigated the role of RAGE-mediated signaling pathways and the therapeutic efficacy of soluble RAGE (sRAGE) in Ang II-induced AC, using both a human aortic smooth muscle cell (HAoSMC) model, and an in vivo apolipoprotein E knockout (ApoE KO) mouse model. According to our data, Ang II significantly increased the calcification of HAoSMCs, and the associated activation of RAGE was mediated by subsequent HMGB1 release through Angiotensin II type 1 receptor activation. Both HMGB1 neutralizing antibody and sRAGE inhibited Ang II-induced calcium deposition. Furthermore, sRAGE attenuated HMGB1 secretion and the activation of RAGE-mediated signaling. The in vivo study indicated that Ang II significantly induced calcium deposition in the aorta, and this was significantly attenuated by sRAGE. Our findings strongly suggest that blockade of RAGE, using sRAGE, effectively attenuates Ang II-induced arterial calcification. [Display omitted] • AT1R- and RAGE-mediated signaling pathways are involved in Ang II-induced VSMC calcification. • These signaling pathways mediate Ang II-induced VSMC osteogenic phenotype switching and vascular calcification. • Soluble RAGE (sRAGE) showed the therapeutic efficacy in an Ang II-induced vascular calcification model. • RAGE is important for mediating Ang II induced vascular calcification. • RAGE may potentially be a therapeutic target for treating vascular calcification. [ABSTRACT FROM AUTHOR]

Because of paucity of published data, we evaluated the 2-year major clinical outcomes between early invasive (EI) and delayed invasive (DI) strategies according to the stage of chronic kidney disease (CKD) in patients with non-ST-segment elevation myocardial infarction (NSTEMI), who underwent a successful newer-generation drug-eluting stent (DES) implantation. A total of 8241 NSTEMI patients were recruited from the Korea Acute Myocardial Infarction Registry (KAMIR). Based on baseline estimated glomerular filtration rate (eGFR; ≥90, 60–89, 30–59, and <30 mL/min/1.73 m2), the patients were classified into groups A (n = 3498), B (n = 3109), C (n = 1178), and D (n = 1178). Thereafter, these 4 groups were sub-classified into the EI and DI groups. Major adverse cardiac events (MACE), defined as all-cause death, recurrent MI (re-MI), and any repeat revascularization, were evaluated. After multivariable-adjusted and propensity score-adjusted analyses, the cumulative incidence of MACE (group A, p = 0.139 and p = 0.103, respectively; group B, p = 0.968 and p = 0.608, respectively; group C, p = 0.111 and p = 0.196, respectively; group D, p = 0.882 and p = 0.571, respectively), all-cause death, re-MI, and any repeat revascularization was similar between the EI and DI groups in the 4 different renal function groups. In the era of newer-generation DES, EI and DI strategies showed comparable major clinical outcomes in patients with NSTEMI and CKD during a 2-year follow-up period. However, to confirm these results, further randomized, large-scale, long-term follow-up studies are needed. [Display omitted] • Current guideline's preference for early invasive (EI) strategy is not based on contemporary drug-eluting stent (DES). • 2-year outcomes were evaluated in patients with non-ST-segment elevation myocardial infarction (NSTEMI) and chronic kidney disease (CKD). • EI and delayed invasive (DI) strategy showed similar results after newer-generation DES implantation. [ABSTRACT FROM AUTHOR]

The 2-year clinical outcomes according to pre-percutaneous coronary intervention (PCI) thrombolysis in myocardial infarction (TIMI) flow grade and reperfusion timing were investigated in patients with non-ST-segment elevation myocardial infarction (NSTEMI) who received newer-generation drug-eluting stents. A total of 7506 NSTEMI patients were divided into 2 groups: early (PCI ≤ 24 hours: n = 6398; pre-PCI TIMI 0/1 [n = 2729], pre-PCI TIMI 2/3 [n = 3669]) and delayed (PCI > 24 hours: n = 1108; pre-PCI TIMI 0/1 [n = 428], pre-PCI TIMI 2/3 [n = 680]) invasive groups. Major adverse cardiac events were defined as all-cause death, recurrent myocardial infarction, or any repeat revascularization. All-cause death (P = 0.005 and 0.009, respectively) and cardiac death (P =.003 and 0.046, respectively) were significantly higher in pre-PCI TIMI 0/1 patients than in pre-PCI TIMI 2/3 patients both in the early and delayed invasive groups. In pre-PCI TIMI 0/1 patients, all-cause death rate was significantly higher in the delayed group (P =.023). In pre-PCI TIMI 2/3 patients, the clinical end point was similar between the 2 groups. An early invasive strategy is preferred to a delayed invasive strategy in reducing all-cause death in patients with pre-PCI TIMI 0/1. However, in patients with pre-PCI TIMI 2/3, both treatment strategies are acceptable. [ABSTRACT FROM AUTHOR]

Abstract: Background: A single nucleotide polymorphism (SNP), V279F, in the lipoprotein-associated phospholipase A2 (Lp-PLA 2 ) gene is known to influence enzyme activity. It is unclear whether Lp-PLA2 exerts pro- or antiatherogenic effects in humans. We investigated the interplay between V279F, Lp-PLA2 activity, oxidative stress and inflammation. Methods: We genotyped 2914 healthy Koreans (43–79years) for the Lp-PLA 2 V279F and measured anthropometric parameters, lipid profile, fatty acid composition, lipid peroxides, inflammatory markers and Lp-PLA2 levels. Results: Lp-PLA2 activity was 24% lower in V/F subjects (n =641) than in those with the V/V genotype (n =2227). Enzyme activity was undetectable in F/F subjects. Lp-PLA2 activity was positively correlated with LDL-cholesterol (r =0.134, P <0.001), ox-LDL (r =0.064, P <0.01), 8-epi-PGF2α (r =0.198, P <0.001), free fatty acid (r =0.082, P <0.001), and fibrinogen (r =0.112, P <0.01) levels. Additionally, ox-LDL, 8-epi-PGF2α, free fatty acid, and fibrinogen levels were positively correlated with hs-CRP. V279F was associated with LDL-cholesterol and arachidonic acid (AA) in serum phospholipid. F/F subjects had lower LDL-cholesterol than V/V subjects (V/V: 120.9±0.69, V/F: 119.4±1.26, F/F: 109.2±4.84mg/dl, P =0.025). A significant association between the F/F genotype and increasing AA in serum phospholipids was found in subjects with high LDL-cholesterol (≥130mg/dl) (P =0.003) but not in those with low LDL-cholesterol (<130mg/dl). F/F subjects in the high LDL-cholesterol group had CRP concentrations about three times higher than those with V/V or V/F genotypes (V/V: 1.25±0.09, V/F: 0.97±0.12, F/F: 3.20±0.88mg/dl, P <0.001). Conclusions: The recessive effects of Lp-PLA 2 V279F on LDL-cholesterol and significant correlations between Lp-PLA2 activity and LDL-cholesterol, 8-epi-PGF2α and fibrinogen support a pro-oxidative or pro-atherogenic role for this enzyme. Paradoxically, the combination of the complete deficiency of Lp-PLA2 activity and high LDL-cholesterol enhanced lipid peroxidation and inflammation. [Copyright &y& Elsevier]

Abstract: Obesity is closely associated with low-grade inflammation. The Gly82Ser (G82S) polymorphism in the receptor for the advanced glycation end products (RAGE) gene related to RAGE expression is also involved in inflammatory response. We examined the association between RAGEG82S and obesity on soluble RAGE (sRAGE) and inflammatory markers in Korean men. The following were measured: anthropometric and biochemical parameters, RAGEG82S polymorphism, sRAGE, advanced glycation end products (AGEs), and inflammatory markers in men (n = 1252; range, 30-70 years; body mass index [BMI], ≥18.5 kg/m2). Allele frequencies satisfied Hardy-Weinberg Equilibrium (G/G: 72.2%, G/S: 25.5%, S/S: 2.3%). RAGEG82S (β-coefficient = −0.384, P < .001) and BMI (β-coefficient = −0.168, P = .001) were major factors affecting sRAGE concentrations. In all subjects, those with ‘S/S’ homozygotes showed the lowest levels of sRAGE (G/G: 1036.3 ± 40.3, G/S: 807.0 ± 49.6, S/S: 443.0 ± 47.8 pg/mL) before (P < .001) and after adjusted for age, BMI, cigarette smoking, and alcohol drinking (P < .001). When subdivided according to BMI of 25 kg/m2 (Asian Pacific guideline), obese subjects (BMI ≥25 kg/m2) had significantly lower levels of sRAGE (831.7 ± 36.7 vs 1022.7 ± 47.8 pg/mL, P = .009) and higher levels of high sensitivity C-reactive protein (hs-CRP) (1.10 ± 0.07 vs 0.72 ± 0.05 mg/dL, P < .001) compared with nonobese subjects (BMI <25 kg/m2). Particularly in obese subjects, S/S carriers showed significantly higher concentrations of AGEs (P = .012) and hs-CRP (P = .006) than G allele carriers, whereas nonobese people had no significant RAGEG82S-related differences in AGEs (P = .743) and hs-CRP (P = .436). In conclusion, G allele at RAGEG82S may be more associated with inflammatory markers under obese status than nonobese conditions. In this case, it may help to suggest proper dietary modification for controlling obesity to people with genetic variants. [Copyright &y& Elsevier]

Purpose: Koreans are recently at higher risk for coronary heart disease than are the Japanese. We aimed to evaluate levels of carotid intima-media thickness (IMT) and coronary risk factors in Korean and Japanese men in the post–World War II birth cohort. Methods: We conducted a population-based study of 352 randomly selected healthy men 40 to 49 years of age: 102 Koreans in Ansan City, Gyeonggi-do, Korea and 250 Japanese in Kusatsu City, Shiga, Japan. Imaging carotid IMT by ultrasonography and other procedures were standardized. Analyzing blood samples and reading carotid IMT were performed at the University of Pittsburgh. Results: Despite more favorable or similar features in coronary risk factors as compared to Japanese men, the Korean men had a higher crude IMT level than the Japanese men (mean ± standard error, 0.655 ± 0.008 mm vs 0.616 ± 0.005 mm, respectively, p < 0.0001). The difference in the levels of carotid IMT significantly remained after adjusting for metabolic and conventional risk factors (0.654 ± 0.008 mm vs. 0.616 ± 0.005 mm, respectively; p < 0.0001). Conclusions: Among men 40 to 49 years of age, Koreans had significantly higher levels of carotid IMT than the Japanese. Factors that underlie the different susceptibility to subclinical atherosclerosis need to be explored. [Copyright &y& Elsevier]

Abstract: Background: Circulating adiponectins have multiple protective roles as anti-diabetic, anti-atherosclerotic, and anti-inflammatory factors. We examined the relationship between plasma adiponectin concentration and other cardiovascular risk in nondiabetic coronary artery disease (CAD) men and the relationship can be maintained even after adjusted for major environmental factors that contribute to adiponectin concentrations. Methods: Nondiabetic CAD men (n =613) were 31–70y and had body mass index (BMI) of 18.5–29.9kg/m2. Results: Circulating adiponectins positively correlated with age and negatively with BMI, waist circumference and % body fat (p-values of all <0.001). Plasma adiponectin concentrations were higher in never-smokers (5.07±0.30μg/ml) than current (4.15±0.12μg/ml) and ex-smokers (3.75±0.20μg/ml) both before and after adjusted for age and adiposity (p =0.002 and p =0.008, respectively), however they were not significantly different according to alcohol drinking status. After adjusted for age, adiposity and cigarette smoking, plasma adiponectin still have positive correlations with HDL cholesterol, apolipoprotein AI and LDL particle size, and inversely with fasting triglyceride, atherogenic index, insulin resistance and C-reactive protein (CRP). However there was no significant relationships between adiponectin and apolipoprotein B, total cholesterol or LDL cholesterol. In subset analysis by tertile adiponectin concentrations (lowest: <2.92, moderate: 2.92≤adiponectin<4.75, highest: ≥4.75μg/ml), ‘moderate’ and ‘highest’ adiponectin groups had lower triglyceride (p <0.001), lower atherogenic index (p =0.001), lower fasting insulin (p =0.004), lower insulin resistance (p =0.001), lower CRP (p =0.001), higher HDL cholesterol (p <0.001), higher apolipoprotein AI (p =0.005) and higher LDL particle size (p <0.001) as compared with ‘lowest’ adiponectin group when adjusted for age, adiposity and cigarette smoking. Platelets were lower in ‘highest’ adiponectin groups as compared with ‘lowest’ and ‘moderate’ adiponectin group after the adjustment. However, there was no significant difference in total cholesterol (p =0.145), LDL cholesterol (p =0.145), apolipoprotein B (p =0.222) and fasting glucose (p =0.157). Conclusion: An increase of adiponectin concentrations or the maintenance of higher concentration may be negatively associated with cardiovascular risk factors in nondiabetic CAD male patients, independent of adiposity and smoking status. [Copyright &y& Elsevier]

Abstract: The no-reflow phenomenon is frequently associated with adverse outcomes in patients undergoing percutaneous coronary intervention (PCI). We describe two cases in which the no-reflow phenomenon developed during PCI and was successfully resolved by direct intracoronary aspiration using the Export aspiration catheter. [Copyright &y& Elsevier]

Abstract: Background: The effect of simvastatin on DNA damage in hypercholesterolemic patients was investigated, and the relationship between the C242T polymorphism of the NADPH oxidase p22phox gene and the antioxidant effects of simvastatin was examined. Methods: Simvastatin (20–40 mg /day) was administered for 8 weeks in 72 hypercholesterolemic patients. DNA damage in lymphocytes was quantified using single-cell gel electrophoresis (COMET assay) by measuring tail DNA (%), tail length (μm) and tail moment (tail length × % tail DNA/100). Results: Simvastatin significantly reduced DNA damage as expressed by tail DNA (%, p &#60; 0.001), tail length (μm, p &#60;0.001) and tail moment on the DNA in lymphocytes (p &#60;0.001) after 8 weeks. The frequencies of the C242T genotypes for CC, TC, and TT were 75.0%, 23.6% and 1.4% in the subjects. In the presence of the 242T allele, there were higher levels of baseline DNA damage and also a greater improvement in the DNA damage after 8 week simvastatin treatment compared with the CC homozygotes. Conclusion: Simvastatin significantly reduced DNA damage of hypercholesterolemic patients. This study showed that simvastatin has a beneficial effect on the improvement of DNA damage in patients with the 242T allele of NADPH oxidase p22phox gene. [Copyright &y& Elsevier]

Background: Although a 1-year duration of dual antiplatelet therapy (DAPT) is used in many patients after drug-eluting stent (DES) implantation, the evidence supporting this duration is uncertain.Objectives: The authors investigated the risk-benefit profile of 1-year vs ≤6-month DAPT after DES using 2 novel scores to risk stratify bleeding and ischemic events.Methods: Ischemic and bleeding risk scores were generated from ADAPT-DES (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents), a multicenter, international, "all-comers" registry that enrolled 8,665 patients treated with DES. The risk-benefit profile of 1-year vs ≤6-month DAPT was then investigated across risk strata from an individual patient data pooled dataset of 7 randomized trials that enrolled 15,083 patients treated with DES.Results: In the derivation cohort, the ischemic score and the bleeding score had c-indexes of 0.76 and 0.66, respectively, and both were well calibrated. In the pooled dataset, no significant difference was apparent in any ischemic endpoint between 1-year and ≤6-month DAPT, regardless of the risk strata. In the overall dataset, there was no significant difference in the risk of clinically relevant bleeding between 1-year and ≤6-month DAPT; however, among 2,508 patients at increased risk of bleeding, 1-year compared with ≤6-month DAPT was associated with greater bleeding (HR: 2.80; 95% CI: 1.12-7.13) without a reduced risk of ischemic events in any risk strata, including those with acute coronary syndromes. These results were consistent in a network meta-analysis.Conclusions: In the present large-scale study, compared with ≤6-month DAPT, a 1-year duration of DAPT was not associated with reduced adverse ischemic events in any risk strata (including acute coronary syndromes) but was associated with greater bleeding in patients at increased risk of bleeding. [ABSTRACT FROM AUTHOR]

We investigated the effect of a beverage containing plant sterols on serum concentrations of triacylglycerol and cholesterol of hypercholesterolemic subjects that consume a low cholesterol diet. Fifty three hypercholesterolemic subjects (fasting LDL-cholesterol > 130 mg/dl) were fed a placebo beverage for 4 weeks followed by feeding a test beverage containing plant sterols for 8 weeks in a single-blind, randomized cross-over study. The subjects were instructed to maintain the same amount of dietary intake of fat and cholesterol during the study. After 4 weeks of treatment with a beverage containing of 1.6 g/d of plant sterols, subjects whose concentrations of LDL-cholesterol did not decrease by 15% received 3.2 g/d of plant sterols. The total study population who completed the whole protocol was 45 subjects (15 males, 30 females, average age 56). At baseline, the average dietary daily intakes of saturated fat and cholesterol were relatively low with 11.12 g and 135.2 mg, respectively. After 8 week treatment with plant sterols, serum concentrations of total cholesterol and LDL-cholesterol were decreased significantly by 4.38% (p < 0.05), 8.28% (p < 0.05) respectively. However, concentrations of HDL-cholesterol and triacylglycerol did not change significantly. We conclude that a beverage containing plant sterols decrease serum total cholesterol and LDL-cholesterol concentrations significantly in subjects with relatively low dietary cholesterol intake. [Copyright &y& Elsevier]