Long-term prognostic factors for cardiovascular events in patients with chest pain without diabetes mellitus nor significant coronary stenosis.

Chest pain is the most common symptom of coronary artery disease (CAD) and diabetes mellitus (DM) is a well-known single strongest risk factor for cardiovascular diseases. Thus, the impact of CAD nor DM on long-term clinical effects is reported widely, but the prognostic factors of non-DM patients presenting with chest pain without significant CAD are limited. A total of 1,046 patients with chest pain without DM and significant CAD who underwent coronary angiography (CAG) and acetylcholine (ACH) provocation tests were finally enrolled. Propensity score matching and multivariate Cox-proportional hazard ratio analysis were performed to adjust for baseline potential confounders. Major adverse cardiac and cerebrovascular events (MACCE) were defined as the composite of total death, myocardial infarction (MI), revascularization, stroke, and recurrent angina. This study aimed to evaluate the long-term prognostic factors for MACCE in patients with chest pain without DM and CAD up to 5 years. Coronary artery spasm (CAS) was the most common cause of chest pain. However, long-term MACCE of CAS was not worse than those of patients with chest pain without CAS when patients with CAS had subsequent optimal antianginal medication therapy. However, a recurrent chest pain remains a problem even with continuous antianginal medication therapy. Up to 5 years, the incidence of MACCE was in 7.3%, including recurrent angina 6.9%. Dyslipidemia (HR: 2.010, 95% CI 1.166-3.466, P = 0.012), mild-moderate (30-70%) coronary stenosis (HR: 2.369, 95% CI 1.118-5.018, P = 0.024), the use of aspirin (HR: 2.885, 95% CI 1.588-5.238, P < 0.001), and the use of nitrates (HR: 1.938, 95% CI 1.094-3.433, P = 0.023) were independent risk factors for MACCE. Among the patients with chest pain without DM and significant CAD, the incidence of MACE were rare, but recurrent angina was still a challenging problem who had treated with antianginal medications.

Balloon-expandable cobalt chromium stent versus self-expandable nitinol stent for the Atherosclerotic Iliac Arterial Disease (SENS-ILIAC Trial) Trial: a randomized controlled trial.

Iliac artery angioplasty with stenting is an effective alternative treatment modality for aortoiliac occlusive diseases. Few randomized controlled trials have compared the efficacy and safety between self-expandable stent (SES) and balloon-expandable stent (BES) in atherosclerotic iliac artery disease. In this randomized, multicenter study, patients with common or external iliac artery occlusive disease were randomly assigned in a 1:1 ratio to either BES or SES. The primary end point was the 1-year clinical patency, defined as freedom from any surgical or percutaneous intervention due to restenosis of the target lesion after the index procedure. The secondary end point was a composite event from major adverse clinical events at 1 year. A total of 201 patients were enrolled from 17 major cardiovascular intervention centers in South Korea. The mean age of the enrolled patients was 66.8 ± 8.5 years and 86.2% of the participants were male. The frequency of critical limb ischemia was 15.4%, and the most common target lesion was in the common iliac artery (75.1%). As the primary end point, the 1-year clinical patency as primary end point was 99% in the BES group and 99% in the SES group (p > 0.99). The rate of repeat revascularization at 1 year was 7.8% in the BES group and 7.0% in the SES group (p = 0.985; confidence interval, 1.011 [0.341-2.995]). In our randomized study, the treatment of iliac artery occlusive disease with self-expandable versus balloon-expandable stent was comparable in 12-month clinical outcomes without differences in the procedural success or geographic miss rate regardless of the deployment method in the distal aortoiliac occlusive lesion (ClinicalTrials.gov, NCT01834495).

Efficacy and safety of cilostazol-based triple antiplatelet therapy compared with clopidogrel-based dual antiplatelet therapy in patients with acute ST-elevation myocardial infarction undergoing percutaneous coronary intervention: A multicenter, randomized, open-label, phase 4 trial.

BACKGROUND: Previous studies reported that compared to conventional dual antiplatelet therapy (DAT; aspirin + clopidogrel), triple antiplatelet therapy (TAT), involving the addition of cilostazol to DAT, had better clinical outcomes in patients with ST-elevation myocardial infarction (STEMI). However, the optimal duration of TAT is yet to be determined. METHODS: In total, 985 patients with STEMI who underwent primary percutaneous coronary intervention (PCI) with drug-eluting stents (DESs) were prospectively enrolled in 15 PCI centers in South Korea and China. We randomly assigned patients into 3 groups: DAT (aspirin and clopidogrel for 12 months), TAT 1M (aspirin, clopidogrel, and cilostazol for 1 month), and TAT 6M (aspirin, clopidogrel, and cilostazol for 6 months). The primary endpoint was 1-year major adverse cardiovascular events (MACEs), defined as a composite of all-cause death, recurrent myocardial infarction, stroke, or repeat revascularization. RESULTS: The primary endpoint did not differ among the 3 groups (8.8% in DAT, 11.0% in TAT 1M, and 11.6% in TAT 6M; hazard ratio for TAT 1M vs DAT, 1.302; 95% confidence interval [CI], 0.792-2.141; P = .297; hazard ratio for TAT 6M vs DAT, 1.358; 95% CI, 0.829-2.225; P = .225). With respect to in-hospital outcomes, more bleeding events occurred in the TAT group than in the DAT group (1.3% vs 4.7% vs 2.6%, P = .029), with no significant differences in major bleeding events. Additionally, the TAT group had a higher incidence of headaches (0% vs 1.6% vs 2.6%, P = .020). CONCLUSIONS: The addition of cilostazol to DAT did not reduce the incidence of 1-year MACEs compared with DAT alone. Instead, it may be associated with an increased risk of drug intolerance and side effects, including in-hospital bleeding and headaches.

Immediate versus staged complete revascularization in patients with ST-segment elevation myocardial infarction and multivessel coronary artery disease: results from a prematurely discontinued randomized multicenter trial.

BACKGROUND: We aimed to compare clinical outcomes between immediate and staged complete revascularization in primary percutaneous coronary intervention (PCI) for treating ST-segment elevation myocardial infarction (STEMI) and multivessel disease (MVD). METHODS: A total of 248 patients were enrolled in a prospective, randomized, and multicenter registry. Immediate revascularization was defined as one-time PCI of culprit and non-culprit lesions at the initial procedure. Staged revascularization was defined as PCI of non-culprit lesions at a later date (mean, 4.4 days; interquartile range, 1-11.4), following initial culprit revascularization. The end points were major adverse cardiovascular events (MACE; composite of total death, recurrent myocardial infarction, and revascularization), any individual components of MACE, cardiac death, stent thrombosis, and stroke at 12 months. RESULTS: During a follow-up of 1 year, MACE occurred in 12 patients (11.6%) in the immediate revascularization group and in 8 patients (7.5%) in staged revascularization group (hazard ratio [HR] 1.60, 95% confidence interval [CI] 0.65-3.91). The incidence of total death was numerically higher in the immediate group than in the staged group (9.7% vs 2.8%, HR 3.53, 95% CI 0.97-12.84); There were no significant differences between the 2 groups in risks of any individual component of MACE, cardiac death, stroke, and in-hospital complications, such as need for transfusion, bleeding, acute renal failure, and acute heart failure. This study was prematurely terminated due to halt of production of everolimus-eluting stents (manufactured as PROMUS Element by Boston Scientific, Natick, Massachusetts). CONCLUSIONS: Due to its limited power, no definite conclusion can be drawn regarding complete revascularization strategy from the present study. Further large randomized clinical trials would be warranted to confirm optimal timing of complete revascularization for patients with STEMI and MVD.

Long-term clinical outcomes following successful percutaneous coronary intervention in patients with extremely long coronary chronic total occlusion lesions.

BACKGROUND: Lesion length is related to worse clinical outcomes following percutaneous coronary intervention (PCI) for the treatment of chronic total occlusion (CTO). However, the data to confirm the association between extremely long lesions and clinical hard endpoints have been limited. Therefore, we investigated the impact of extremely long CTO lesions (≥50 mm, treated lesion length) on the long-term clinical outcomes following successful PCI. METHODS: A total of 333 consecutive patients with CTO who underwent successful PCI with drug-eluting stents (DESs) were allocated to either the extremely long or the short CTO group according to their CTO lesion length. The 5-year clinical outcomes were compared between the two groups. The incidence of myocardial infarction, cardiac death (CD), revascularization, and major adverse cardiovascular events (MACE) was higher in the extremely long CTO group. The 5-year clinical outcomes were analyzed using the Cox hazard ratio (HR) model. RESULTS: In the entire study population, the extremely long CTO lesion was an independent predictor for higher rate of revascularization, MACE, CD, or mortality. CONCLUSIONS: In our study, CTO patients with extremely long lesions (≥50 mm) who underwent successful PCI were associated with a higher risk of worse long-term clinical outcomes, including hard clinical endpoints such as CD and mortality even in the DESs era.

Effects of delayed hospitalization on the 3-year clinical outcomes of patients with or without diabetes who had non-ST-segment-elevation myocardial infarction and underwent new-generation drug-eluting stent implantation.

Clinical outcomes after non-ST-segment-elevation myocardial infarction (NSTEMI) in patients with (symptom-to-door time [SDT] ≥ 24 h) or without (SDT < 24 h) delayed hospitalization among patients with or without diabetes were compared. From the Korea Acute Myocardial Infarction Registry-National Institute of Health, a total of 4517 patients with NSTEMI who underwent new-generation drug-eluting stents implantation were recruited and they were classified into the diabetes mellitus (DM) and non-DM groups. These two groups were subdivided into groups with and without delayed hospitalization. The primary clinical outcome was the occurrence of major adverse cardiac and cerebrovascular events (MACCE), defined as all-cause death, recurrent myocardial infarction, repeat coronary revascularization, and stroke. The secondary clinical outcome was the occurrence of individual components of MACCE and stent thrombosis. Although after multivariable and propensity score-adjusted analyses in the DM group, the primary and secondary clinical outcomes between the SDT < 24 h and SDT ≥ 24 h groups were similar; in the non-DM group, all-cause (p = 0.003 and p = 0.007, respectively) and cardiac (p = 0.001 and p = 0.008, respectively) death rates were significantly higher in the SDT ≥ 24 h group than in the SDT < 24 h group. Our results suggested that there was no significant difference in prognosis between diabetic patients with and without delayed SDT, but delayed SDT was associated with poor prognosis in nondiabetic patients.

Korean vs. Western Exercise Capacity Nomograms for Korean Patients With Cardiovascular Disease.

BACKGROUND: Exercise capacity is known to be an independent predictor of cardiovascular events and mortality. However, most previous studies were based on Western populations. Further study is warranted for Asian patients according to ethnic or national standards. We aimed to compare prognostic values of Korean and Western nomograms for exercise capacity in Korean patients with cardiovascular disease (CVD). METHODS: In this retrospective cohort study, we enrolled 1,178 patients (62 ± 11 years; 78% male) between June 2015 and May 2020, who were referred for cardiopulmonary exercise testing in our cardiac rehabilitation program. The median follow-up period was 1.6 years. Exercise capacity was measured in metabolic equivalents by direct gas exchange method during the treadmill test. The nomogram for exercise capacity from healthy Korean individuals and a previous landmark Western study was used to determine the percentage of predicted exercise capacity. The primary endpoint was the composite of major adverse cardiovascular events (MACE; all-cause death, myocardial infarction, repeat revascularization, stroke and hospitalization for heart failure). RESULTS: A multivariate analysis showed that the risk of primary endpoint was more than double (hazard ratio [HR], 2.20; 95% confidence interval [CI], 1.10-4.40) in the patients with lower exercise capacity (< 85% of predicted) by Korean nomogram. The lower exercise capacity was one of the strong independent predictors along with left ventricular ejection fraction, age, and level of hemoglobin. However, the lower exercise capacity by Western nomogram could not predict the primary endpoint (HR, 1.33; 95% CI, 0.85-2.10). CONCLUSION: Korean patients with CVD with lower exercise capacity have higher risk of MACE. Considering inter-ethnic differences in cardiorespiratory fitness, the Korean nomogram provides more suitable reference values than the Western nomogram to determine lower exercise capacity and predict cardiovascular events in Korean patients with CVD.

Impact of complete revascularization on long-term clinical outcomes for patients with diabetes mellitus and coronary chronic total occlusion lesion.

Diabetes mellitus (DM) is a substantial risk factor in developing coronary artery disease (CAD), coronary chronic total occlusion (CTO) lesions are discovering 10-35% in patients who underwent coronary angiography. This study compares the long-term clinical outcomes of two treatment strategies, percutaneous coronary intervention (PCI) with complete recanalization versus medication therapy (MT) with CTO lesion in DM patients with CTO. This study is a single-center, prospective, all-comer registry designed to reflect "real world" practice since 2004. Of a total of 4909 consecutive patients were diagnosed with significant CAD by coronary angiography (CAG). A total of 372 patients has DM and CTO lesions. Patients were divided into the PCI group (n = 184) and the MT group (n = 179). The primary endpoint, defined as the composite of death or myocardial infarction (MI), was compared between the two groups up to 5 years. In addition, inverse probability weighting (IPTW) analysis, derived from the logistic regression model, was performed to adjust for potential confounders. Compared to the MT group, the PCI group was associated with a significantly reduced incidence of the primary endpoint before [hazard ratio; HR 0.267, 95% confidence interval (CI) 0.116-0.614] and after (HR 0.142, 95% CI 0.032-0.629) adjusting confounding factors by IPTW. Complete revascularization by CTO-PCI with MT in DM patients should be the preferred treatment strategy compared with the MT alone strategy since it reduces the composite of death or MI up to 5 years.

Stress-associated neurobiological activity is linked with acute plaque instability via enhanced macrophage activity: a prospective serial 18F-FDG-PET/CT imaging assessment.

AIMS: Emotional stress is associated with future cardiovascular events. However, the mechanistic linkage of brain emotional neural activity with acute plaque instability is not fully elucidated. We aimed to prospectively estimate the relationship between brain amygdalar activity (AmygA), arterial inflammation (AI), and macrophage haematopoiesis (HEMA) in acute myocardial infarction (AMI) as compared with controls. METHODS AND RESULTS: 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) imaging was performed within 45 days of the index episode in 62 patients (45 with AMI, mean 60.0 years, 84.4% male; 17 controls, mean 59.6 years, 76.4% male). In 10 patients of the AMI group, serial 18F-FDG-PET/CT imaging was performed after 6 months to estimate the temporal changes. The signals were compared using a customized 3D-rendered PET reconstruction. AmygA [target-to-background ratio (TBR), mean ± standard deviation: 0.65 ± 0.05 vs. 0.60 ± 0.05; P = 0.004], carotid AI (TBR: 2.04 ± 0.39 vs. 1.81 ± 0.25; P = 0.026), and HEMA (TBR: 2.60 ± 0.38 vs. 2.22 ± 0.28; P < 0.001) were significantly higher in AMI patients compared with controls. AmygA correlated significantly with those of the carotid artery (r = 0.350; P = 0.005), aorta (r = 0.471; P < 0.001), and bone marrow (r = 0.356; P = 0.005). Psychological stress scales (PHQ-9 and PSS-10) and AmygA assessed by PET/CT imaging correlated well (P < 0.001). Six-month after AMI, AmygA, carotid AI, and HEMA decreased to a level comparable with the controls. CONCLUSION: AmygA, AI, and HEMA were concordantly enhanced in patients with AMI, showing concurrent dynamic changes over time. These results raise the possibility that stress-associated neurobiological activity is linked with acute plaque instability via augmented macrophage activity and could be a potential therapeutic target for plaque inflammation in AMI.

Impact of renin angiotensin system inhibitor on 3-year clinical outcomes in acute myocardial infarction patients with preserved left ventricular systolic function: a prospective cohort study from Korea Acute Myocardial Infarction Registry (KAMIR).

BACKGROUND: Patients with acute myocardial infarction (AMI) are usually treated with angiotensin-converting enzyme inhibitors (ACEIs), or angiotensin receptor blockers (ARBs) if ACEIs are not tolerated. However, there is no data regarding the impact of switching from ACEIs to ARBs on long-term clinical outcomes in AMI patients with preserved left ventricular (LV) systolic function especially beyond 1 year. To investigate the effectiveness of treatment with ACEIs or ARBs on clinical outcomes over 3 years in AMI patients with preserved LV systolic function following percutaneous coronary intervention. METHOD: It is a prospective cohort study using data from a nationwide large scale registry with 53 hospitals involved in treatment of acute myocardial infarction (AMI) in Korea. Between March 2011 and September 2015, we enrolled 6236 patients with AMI who underwent primary percutaneous coronary intervention and had a left ventricular ejection fraction ≥ 50%. Main outcome measures composite of total death or recurrent AMI over 3 years after AMI. Patients were divided into an ACEI group (n = 2945), ARB group (n = 2197), or no renin-angiotensin system inhibitor (RASI) treatment (n = 1094). We analyzed patients who changed treatment. Inverse probability of treatment weighting (IPTW) analysis was also performed. RESULTS: After the adjustment with inverse probability weighting, the primary endpoints at 1 year, AMI patients receiving ACEIs showed overall better outcomes than ARBs [ARBs hazard ratio (HR) compared with ACEIs 1.384, 95% confidence interval (CI) 1.15-1.71; P = 0.003]. However, 33% of patients receiving ACEIs switched to ARBs during the first year, while only about 1.5% switched from ARBs to ACEIs. When landmark analysis was performed from 1 year to the end of the study, RASI group showed a 31% adjusted reduction in primary endpoint compared to patients with no RASI group (HR, 0.74; 95% CI 0.56-0.97; P = 0.012). CONCLUSIONS: This result suggests that certain patients got benefit from treatment with ACEIs in the first year if tolerated, but switching to ARBs beyond the first year produced similar outcomes. RASI beyond the first year reduced death or recurrent AMI in AMI patients with preserved LV systolic function. CRIS Registration number: KCT0004990.

Impact of chronic outward force on arterial responses of proximal and distal of long superficial femoral artery stent.

BACKGROUND: Self-expanding nitinol stent (SENS) implantation is commonly oversized in the superficial femoral artery (SFA), and leads to chronic outward force (COF) and in-stent restenosis (ISR). This study aimed to investigate the impact of COF of oversizing SENS on ISR of SFA. METHODS: In patients with implanted SENS in SFA, intimal hyperplasia especially between proximal segment and distal segment was evaluated by quantitative angiography, and the impact of COF on mid-term angiographic outcomes was investigated. In addition, porcine model with implanted SENS was used to evaluate the impact of COF on angiographic and histopathologic outcomes at 1 month. Excised stented arteries were evaluated by histopathologic analysis. RESULTS: We analyzed 65 SENS in 61 patients with follow-up angiography at 6 months to 1 year. The baseline diameter was 6.8 ± 0.71 mm and length were 97.0 ± 33.8 mm for the SENS. The ratio of the diameter of the stent to the reference vessel was 1.3 ± 0.24 at the proximal portion and 1.53 ± 0.27 at the distal portion (P < 0.001). In the long SFA stent, stent-to-vessel ratio was significantly higher in the distal stent than in the proximal stent (1.3 ± 0.2 vs. 1.55 ± 0.25, P = 0.001). ISR incidence was higher at the distal stent (37.3% vs 52.6%, P = 0.029). All 11 pigs survived for 4 weeks after SENS implantation. The vessel diameter was 4.04 ± 0.40 mm (control group) vs 4.45 ± 0.63 mm (oversized group), and the implanted stent diameter was 5.27 ± 0.46 mm vs. 7.18 ± 0.4 mm (P = 0.001). The stent-to-vessel diameter ratio was 1.31 ± 0.12 versus 1.63 ± 0.20 (P < 0.001). After 4 weeks, restenosis % was 29.5 ± 12.9% versus 46.8 ± 21.5% (P = 0.016). The neointimal area was 5.37 ± 1.15 mm2 vs. 8.53 ± 5.18 mm2 (P = 0.05). The restenosis % was 39.34 ± 8.53% versus 63.97 ± 17.1% (P = 0.001). CONCLUSIONS: COF is an important cause of restenosis in the distal portion of the SFA stent. Optimal sizing of the SFA stent is important to reduce the incidence of restenosis. Therefore, COF was an important factor of restenosis following distal SFA stenting.

Age and sex dependent association of uric acid and incident hypertension.

BACKGROUND AND AIMS: A previous meta-analysis suggested that the relationship between hyperuricemia and hypertension may be stronger in younger individuals and women. We aimed to investigate the age and sex dependent association of uric acid (UA) and incident hypertension. METHODS AND RESULTS: We analyzed data from the Health Examinees Study, a community-based prospective cohort study conducted in Korea from 2004 to 2013. It included 29,088 non-hypertensive subjects aged 40-79 (age, 52.5 ± 7.8 years; men, 31.4%) who had serum UA measurement and participated in the follow-up survey. The risk factors of hypertension were assessed using Cox regression. Over a mean 3.8 years of follow-up, 1388 men (15.2%) and 1942 women (9.7%) were newly diagnosed with hypertension. Upon age- and sex-based stratification, the risk of hypertension was highest in hyperuricemic subjects aged 40-49 years (HR: women, 2.16; men, 1.30). Across the entire cohort, the risk of incident hypertension was higher in groups with higher serum UA levels, and highest in women aged 40-49 years (HR, 1.44; P < 0.001). On multivariable linear regression analysis, the higher the baseline serum UA level, the greater the increase in blood pressure during follow-up, and this effect was strongest in women aged 40-49 years (ß = 0.87 and P < 0.01 for systolic blood pressure). CONCLUSIONS: The relationship between uric acid and incident hypertension tended to be dependent on age and sex. Younger women are at highest risk of UA-related incident hypertension.

Initial diastolic dysfunction is a powerful predictor of 5-year mortality in peripheral arterial disease patients undergoing percutaneous transluminal angioplasty.

Peripheral arterial disease (PAD) and heart failure share common risks and are associated with increased morbidity and mortality. However, it is unknown whether cardiac function can be an independent predictor of long-term mortality in patients with PAD. In total, 902 patients who underwent percutaneous transluminal angioplasty for PAD were enrolled. The patients were categorized into three groups according to the left ventricular ejection fraction (LVEF): reduced EF (< 40%, n = 62); mid-range EF (40-49%, n = 76); and preserved EF (≥ 50%, n = 764). Echocardiographic (EF, ratio of mitral inflow velocity to annular velocity E/e' ≥ 15, and others) and clinical parameters were tested using stepwise logistic regression analysis to determine independent predictors of 5-year mortality. A higher proportion of patients with reduced EF had ischemic heart disease than those with preserved EF (77.4% vs. 56.8%, p < 0.001). Up to 5 years, patients with reduced EF and mid-range EF showed a higher incidence of total death than those with normal EF. However, there was no difference in the incidence of myocardial infarction, stroke, and revascularization among the three groups. After multivariable adjustment, the ratio of E/e' ≥ 15 was the only strong predictor of total mortality (hazard ratio 6.14; 95% confidence interval 3.7-10.1; p < 0.01). Patients with PAD and reduced EF undergoing PTA had a higher incidence of total death during the 5-year follow-up. Initial tissue Doppler E/e' ≥ 15, a non-invasive estimate of left atrial filling pressure, was the only independent predictor of long-term mortality. The relationship between PAD and HF.

A relationship between unrecognized anaemia and the development of type 2 diabetes mellitus in patient with cardiovascular risks.

Studies on anaemia in diabetic patients are well known. However, the data regarding association of anaemia on the development of diabetes mellitus (DM) are very limited. We aimed to evaluate the association of anaemia on the development of DM and major clinical outcomes in a series of the Korean population during 5-year clinical follow-up. The patients were retrospectively enrolled using the electronic database of Korea University Guro Hospital from January 2004 to February 2013. A total of 17 515 subjects without a history of DM were analysed. The World Health Organization definition of anaemia was used. Patients were divided into the anaemia group (n = 2907 patients) and the non-anaemia group (n = 14 608 patients). The primary endpoint was the development of DM. To adjust baseline potential confounders, a propensity score matching (PSM) analysis was performed. After PSM analysis, two matched groups (2731 pairs) were generated and their baselines characteristics were balanced. During 5-year follow-up, the anaemia group had a higher incidence of type 2 DM (10.7% vs 7.7%; hazard ratio [HR], 1.356; 95% confidence interval [CI], 1.021-1.802; P = .035), and total death (2.6% vs 1.2%; HR, 2.449; 95% CI, 1.337-4.486; P = .004) compared to the non-anaemia group. In the present study, anaemia was associated with higher rate of the development of DM and mortality during 5-year clinical follow-up. A randomized trial is needed to determine whether this results can be reproducible or not for the final conclusion.

Impact of Sleep-Disordered Breathing on Functional Outcomes in Ischemic Stroke: A Cardiopulmonary Coupling Analysis.

BACKGROUND AND PURPOSE: Cardiopulmonary coupling (CPC) analysis is an easily assessable method to evaluate sleep-disordered breathing (SDB); however, its prognostic impact in patients with acute ischemic stroke needs to be investigated. We performed a CPC analysis using Holter monitoring at the early stage of noncardioembolic ischemic stroke to investigate the prognostic effect of SDB on functional impairment at the 3-month follow-up. METHODS: A total 615 patients with acute noncardioembolic ischemic stroke who underwent Holter monitoring within 30 days of stroke onset were enrolled from a multicenter, prospective, all-comer cohort. CPC analysis was conducted, and SDB was defined by the presence of narrow-band coupling during sleep time. We investigated the association between SDB and functional impairment at 3 months as measured by the modified Rankin Scale. RESULT: Narrow-band coupling was present in 191 (31.1%) of 615 patients (mean age 64.5±12.6 years). The narrow-band group showed a significantly higher rate of severe functional impairment (modified Rankin Scale score >2; 45.5% versus 12.9%, P<0.001) and persistent disability (Δmodified Rankin Scale score ≤0; 53.9% versus 39.8%, P<0.001) at the 3-month follow-up. In multivariate analysis, narrow-band coupling was an independent predictor of higher risk of severe and persistent functional impairment at 3 months (odds ratio, 3.98 [95% CI, 2.34-6.78]; P<0.001; and odds ratio, 1.81 [95% CI, 1.23-2.66]; P<0.001, respectively). The results remained consistent after propensity-score matched analysis with 157 patient pairs (C-statistic=0.770). CONCLUSIONS: SDB assessed by CPC analysis at the early stage of ischemic stroke could predict severe and prolonged functional impairment at 3 months. CPC analysis using Holter monitoring can help predicting functional impairment in acute ischemic stroke.

Cilostazol-based triple versus potent P2Y12 inhibitor-based dual antiplatelet therapy in patients with acute myocardial infarction undergoing percutaneous coronary intervention.

Although potent P2Y12 inhibitor-based dual antiplatelet therapy (DAPT) has replaced clopidogrel-based therapy as the standard treatment in patients with acute myocardial infarction (AMI), there is a concern about the risk of bleeding in East Asian patients. We compared the efficacy and safety of cilostazol-based triple antiplatelet therapy (TAT) with potent P2Y12 inhibitor-based DAPT in Korean patients. A total of 4152 AMI patients who underwent percutaneous coronary intervention (PCI) in the Korea Acute Myocardial Infarction Registry were analyzed retrospectively. Patients were divided into two groups: the TAT group (aspirin + clopidogrel + cilostazol, n = 3161) and the potent DAPT group (aspirin + potent P2Y12 inhibitors [ticagrelor or prasugrel], n = 991). Major clinical outcomes at 30 days and 2 years were compared between the two groups using propensity score matching (PSM) analysis. After PSM (869 pairs), there were no significant differences between the two groups in the incidence of total death, cardiac death, myocardial infarction (MI), target vessel revascularization, stent thrombosis, and stroke at 30 days and 2 years. However, the Thrombolysis in Myocardial Infarction (TIMI) major or minor bleeding rates were significantly lower in the TAT group compared with the potent DAPT group at 2 years (6.4% vs. 3.6%, p = 0.006). In Korean AMI patients undergoing PCI, TAT with cilostazol was associated with lower bleeding than the potent P2Y12 inhibitor-based DAPT without increased ischemic risk. These results could provide a rationale for the use of TAT in East Asian AMI patients.

Risk of insulin resistance with statin therapy in individuals without dyslipidemia: A propensity-matched analysis in a registry population.

Several studies suggest the higher vulnerability of individuals with lower low-density lipoprotein cholesterol (LDL-C) levels to diabetes mellitus. However, the discordance between high and low baseline LDL-C levels shown by statin-induced insulin resistance is not fully understood. This study aimed to explore the relationship between baseline LDL-C levels and the risk of statin-induced insulin resistance during statin therapy. In total, 2660 (451 with dyslipidemia and 2209 without dyslipidemia) consecutive patients were enrolled. Their baseline clinical data were adjusted using a propensity score matching analysis, using the logistic regression model. Insulin resistance index was based on the homeostatic model assessment-insulin resistance (HOMA-IR) and was monitored for a median of 2 years. Among the individuals who received statin therapy, those with and without dyslipidemia showed significantly decreased LDL-C levels (all P < .0001) and significantly increased fasting plasma insulin levels (Δ = +24.1%, P = .0230; Δ = +30.1%, P < .0001); however, their glycated haemoglobin A1c and fasting blood glucose levels did not change (all P > .05). Although HOMA-IR was positively associated with statin therapy in individuals with and without dyslipidemia, statistically significant difference during follow-ups was observed only in individuals without dyslipidemia (Δ = +15.6%, P = .1609; Δ = 24.0%; P = .0001). Insulin resistance was higher in statin users without baseline dyslipidemia than in those with dyslipidemia. Thus, statin therapy could increase the risk of statin-induced insulin resistance in individuals with normal baseline cholesterol levels.

Selective ß1-Blockers Are Not Associated With New-onset Diabetes Mellitus in Hypertensive Patients.

BACKGROUND: Although ß-blockers are known to increase new-onset diabetes mellitus (DM), previous evidence have been controversial. It has been suggested that newer vasodilatory ß-blockers yield better glycemic control than older nonselective agents. The aim of this study was to evaluate the diabetogenicity of currently used newer ß-blockers based on ß1 receptor selectivity in a series of Asian population. METHODS: We investigated a total of 65,686 hypertensive patients without DM from 2004 to 2014. Patients with hemoglobin (Hb) A1c ≤6.0%, fasting blood glucose ≤110 mg/dL, and no history of diabetes or diabetic treatment were enrolled for analysis. Patients were divided into the ß-blockers group and non-ß-blockers group. Propensity score matching (PSM) analysis using a logistic regression model was performed to adjust for potential confounders. The primary end point was the cumulative incidence of new-onset DM, defined as a fasting blood glucose ≥126 mg/dL or HbA1c ≥6.5%, and major adverse cardiac and cerebral events (MACCE), defined as a composite of total death, nonfatal myocardial infarction, and cerebrovascular accidents. We investigated predictors of new-onset DM and MACCE based on 2 models, including clinical risk factors and co-medications, respectively. RESULTS: Mean follow-up duration was 30.91 ± 23.14 months in the entire group before adjustment. The ß-blockers group had a significantly higher incidence of new-onset DM and MACCE than the non-ß-blockers group. After PSM, analysis of a total of 2284 patients (1142 pairs, C-statistic = 0.752) showed no difference between the 2 groups in new-onset DM or MACCE. In multivariate analysis after PSM, baseline HbA1c, stroke, heart failure, nonselective ß-blockers, and age were independent predictors of new-onset DM. Selective ß1-blockers did not increase new-onset DM after adjustment for other antihypertensive medication and statins. CONCLUSIONS: In the era of newer ß-blockers, selective ß1-blockers were not associated with new-onset DM. More evidence is needed to verify this relationship and the underlying mechanisms.

Hyperuricaemia and development of type 2 diabetes mellitus in Asian population.

Recently, meta-analysis studies reported that hyperuricaemia is associated with higher incidence of type 2 diabetes mellitus (T2DM), however, there are limited data on the Asian population. The aim of this observational study is to estimate the long-term impact of hyperuricaemia on the new-onset T2DM and cardiovascular events. This study is based on a single-centre, all-comers, and large retrospective cohort. Subjects that visited from January 2004 to February 2014 were enrolled using the electronic database of Korea University Guro Hospital. A total of 10 505 patients without a history of T2DM were analyzed for uric acid, fasting glucose and haemoglobin (Hb) A1c level. Inclusion criteria included both Hb A1c <5.7% and fasting glucose level <100 mg/dL without T2DM. Hyperuricaemia was defined as a uric acid level ≥7.0 mg/dL in men, and ≥6.5 mg/dL in women. To adjust baseline confounders, a propensity score matching (PSM) analysis was performed. The impact of hyperuricaemia on the new-onset T2DM and cardiovascular events were compared with the non-hyperuricaemia during the 5-year clinical follow-up. After PSM, baseline characteristics of both groups were balanced. In a 5-year follow-up, the hyperuricaemia itself was a strong independent predictor of the incidence of new-onset T2DM (HR, 1.78; 95% CI, 1.12 to 2.8). Hyperuricaemia was a strong independent predictor of new-onset T2DM, which suggests a substantial implication for a correlation between uric acid concentration and insulin resistance (or insulin sensitivity). Also, hyperuricaemia is substantially implicated in cardiovascular risks and the further long-term cardiovascular events in the crude population, but it is not an independent predictor of long-term cardiovascular mortality in the matched population.