Association between pre-treatment with statin and its inhibitory effect on the onset of coronary artery disease at the time of coronary computed tomography angiography: a new look at an old medication.

Coronary artery stenosis is often advanced by the time coronary computed tomography angiography (CCTA). Statins are the most important anti-lipidemic medication for improving the prognosis of coronary artery disease (CAD) patients. Although lipid-lowering therapy using statins appears to have been established as a method for preventing CAD, there remains the problem that CAD cannot be completely suppressed. In this study, we investigated whether pre-treatment with statin could significantly inhibit the onset of CAD when patients received CCTA for screening of CAD. The subjects were 1164 patients who underwent CCTA as screening for CAD. CAD was diagnosed when 50% or more coronary stenosis was present in the coronary arteries. Patient backgrounds were investigated by age, gender, body mass index, coronary risk factors [family history of cardiovascular diseases, smoking history, hypertension (HTN), diabetes mellitus (DM), dyslipidemia, chronic kidney disease (CKD) or metabolic sydrome] and medications. Patients were classified into two groups according to the presence or absence of statin pre-administration during CCTA [statin (-) group (n = 804) and (+) group (n = 360)]. Compared with the statin (-) group, the statin (+) group was significantly older and had higher rates of family history, HTN, and DM. The statin (+) group had a significantly higher % CAD than the statin (-) group. Serum levels of low-density lipoprotein cholesterol (LDL-C) were significantly lower in the statin (+) group than in the statin (-) group. There was no significant difference in either high-density lipoprotein cholesterol levels or triglyceride levels between the two groups. Age, male gender, HTN, DM and pre-treatment with statin were all associated with CAD (+) in all patients. In addition, factors that contributed to CAD (+) in the statin (-) group were age, male gender, and DM, and factors that contributed to CAD (+) in the statin (+) group were age, smoking, HTN and % maximum dose of statin. At the time of CCTA, the statin (+) group had a high rate of CAD and coronary artery stenosis progressed despite a reduction of LDL-C levels. To prevent the onset of CAD, in addition to strict control of other coronary risk factors (HTN etc.), further LDL cholesterol-lowering therapy may be necessary.

Association Between the Presence of Coronary Artery Disease or Peripheral Artery Disease and Left Ventricular Mass in Patients Who Have Undergone Coronary Computed Tomography Angiography.

Background: Left ventricular mass (LVM) is a critical marker of future cardiovascular risk. We determined the association between LVM measured by coronary computed tomography angiography (CCTA) and the presence of coronary artery disease (CAD) or peripheral artery disease (PAD) in patients who had undergone CCTA for screening of CAD. Methods: We enrolled 1,307 consecutive patients (66 ± 12 years old, 49% males) who underwent CCTA for screening of CAD at the Fukuoka University Hospital (FU-CCTA registry), and either were clinically suspected of having CAD or had at least one cardiovascular risk factor. Patients with coronary stenosis of ≥ 50% by CCTA were diagnosed as CAD. Patients with an ankle brachial pressure index < 0.9 or who had already been diagnosed with PAD were considered to have PAD. Left ventricular mass index (LVMI), left ventricular ejection fraction (LVEF), end-diastolic volume (EDV) and end-systolic volume (ESV) were measured. The patients were divided into CAD (-) and CAD (+) or PAD (-) and PAD (+) groups. Results: The prevalences of CAD and PAD in all patients were 50% and 4.8%, respectively. Age, %males, %hypertension (HTN), %dyslipidemia (DL), %diabetes mellitus (DM), %smoking and %chronic kidney disease in the CAD (+) group were significantly higher than those in the CAD (-) group. Age, %males, %HTN, %DM and %smoking in the PAD (+) group were significantly higher than those in the PAD (-) group. CAD was independently associated with LVMI (odds ratio (OR): 1.01, 95% confidence interval (CI): 1.01 - 1.02, P < 0.01) in addition to age, male, HTN, DL, DM, and smoking. PAD was also independently associated with LVMI (OR: 1.01, 95% CI: 1.0 - 1.02, P = 0.018) in addition to age, DM, and smoking. Conclusions: LVMI determined by CCTA may be useful for predicting atherosclerotic cardiovascular diseases including both CAD and PAD, although there were considerable differences between %CAD and %PAD in all patients.

Association between Major Adverse Cardiovascular Events and the Liver Fibrosis Score in Patients with and without Coronary Artery Disease: From the FU-CCTA Registry.

The liver fibrosis score reflects the degree of hepatic scarring and has been reported to be associated with cardiovascular disease. Using a coronary artery computed tomography angiography registry at the Fukuoka University Hospital (FU-CCTA registry), we investigated the association between major adverse cardiovascular events (MACEs) and the liver fibrosis score (fibrosis-4 index (FIB-4I)) in 612 patients who underwent CCTA to screen for coronary artery disease and performed a prognosis survey for up to 5 years. The primary endpoint was MACEs (all-cause mortality, acute myocardial infarction, ischemic stroke, coronary revascularization). FIB-4I in all patients and in patients with hypertension (HTN) was significantly higher in the MACE group than in the non-MACE group. The event-free survival rate of MACEs targeting only patients with HTN was significantly lower in patients with a high risk of liver fibrosis (FIB-4I values of 2.67 or higher) than in those with a low or intermediate risk (less than 2.67). However, no significant difference was observed in all patients or in patients without HTN. Finally, FIB-4I and body mass index were independent factors associated with MACEs in patients with HTN. In conclusion, the liver fibrosis score may be an independent predictor of MACEs in hypertensive patients undergoing CCTA.

Association Between Telomere G-Tail Length and Coronary Artery Disease or Statin Treatment in Patients With Cardiovascular Risks　- A Cross-Sectional Study.

Background: The utility of telomere G-tail length to predict coronary artery disease (CAD) remains controversial. CAD results from coronary artery narrowing due to cholesterol and lipid accumulation, augmented by inflammatory cells and other factors. This study explored the significance of telomere G-tail length in suspected CAD patients. Methods and Results: In all, 95 patients with suspected CAD or ≥1 cardiac risk factor underwent coronary computed tomography angiography (CCTA). We measured leukocyte telomere length and G-tail length using a hybrid protection method, and diagnosed the presence of CAD using CCTA. Associations between G-tail length and the presence of CAD, the number of stenosed coronary arteries, and brachial-ankle pulse wave velocity (baPWV) were analyzed. No significant difference was observed in G-tail length when comparing groups with or without CAD or statin treatment. However, in the non-statin group, G-tail length was significantly shorter in patients with 3-vessel disease compared with 1-vessel disease. Dividing the group using a baPWV of 1,300 cm/s, telomere G-tail length was significantly shorter in the high-risk (baPWV ≥1,300 cm/s) group. Conclusions: The clinical utility of telomere G-tail length as a CAD risk indicator seems limited. There was a trend for longer telomere G-tail length in the statin-treated group. Moreover, telomere G-tail length was reduced in patients at high-risk of cardiovascular events, aligning with the trend of a shortening in telomere G-tail length with CAD severity.

Investigating the Association between Coronary Artery Disease and the Liver Fibrosis-4 Index in Patients Who Underwent Coronary Computed Tomography Angiography: A Cross-Sectional Study.

Liver fibrosis scores, indicative of hepatic scarring, have recently been linked to coronary artery disease (CAD). We investigated the association between CAD and the fibrosis-4 index (FIB-4I) in patients who underwent coronary computed tomography angiography (CCTA). This study included 1244 patients who were clinically suspected of having CAD. The presence or absence of CAD was the primary endpoint. FIB-4I was higher in the CAD group than in the non-CAD group (1.95 ± 1.21 versus [vs.] 1.65 ± 1.22, p < 0.001). FIB-4I was also higher in the hypertension (HTN) group than in the non-HTN group (1.90 ± 1.32 vs. 1.60 ± 0.98, p < 0.001). In all patients, high FIB-4I (≥2.67) was a predictor of presence of CAD (odds ratio [OR]: 1.92, 95% confidence interval [CI]: 1.30-2.83, p = 0.001), and low FIB-4I (≤1.29) was proven to be a predictor of absence of CAD (OR: 0.65, 95% CI: 0.48-0.88, p = 0.006). In the HTN group, high and low FIB-4I levels, were found to be predictors for CAD (OR: 2.01, 95% CI: 1.26-3.21, p < 0.001 and OR: 0.65, 95% CI: 0.45-0.94, p < 0.022, respectively), in particular. FIB-4I may serve as a diagnostic indicator of the presence or absence of CAD in hypertensive patients undergoing CCTA.

Association Between Major Adverse Cardiovascular Events and the Gensini Score or Coronary Artery Calcification Score in Hypertensive Patients Who Have Undergone Coronary Computed Tomography Angiography.

Background: From the Fukuoka University Coronary Computed Tomography Angiography (FU-CCTA) registry, we present major adverse cardiovascular events (MACEs) in hypertensive patients who have undergone CCTA, and the association between MACEs and the Gensini score of coronary arteries or the coronary artery calcification (CAC) score. Methods: Of the patients who underwent CCTA for coronary artery disease (CAD) screening at Fukuoka University Hospital, 318 hypertensive patients who had at least one cardiovascular risk factor or suspected CAD were enrolled. The patients were divided into two groups: MACEs and non-MACEs groups. The severity of atherosclerosis of coronary arteries was assessed by the Gensini score. The CAC score was also defined by computed tomography (CT) images at the time of CCTA. A primary endpoint was MACEs (all-cause death, ischemic stroke, acute myocardial infarction, coronary revascularization). The patients were followed for up to 5 years. Results: The patients were 68 ± 10 years, and 50% were males. The percentages of smoking, dyslipidemia, diabetes, and chronic kidney disease were 39%, 70%, 26% and 37%, respectively. The %males, %smoking, CAC score and Gensini score in the MACEs group were significantly higher than those in the non-MACEs group. On the other hand, the differences in age, dyslipidemia, diabetes, or chronic kidney disease between the groups were not seen. A multivariate analysis was performed regarding the presence or absence of MACE by logistic regression analysis of the CAC score or Gensini score in addition to conventional risk factors as independent variables. A Cox regression analysis revealed significant relationships for both the CAC score (P = 0.043) and the Gensini score (P = 0.008). Conclusions: The CAC score and the Gensini score could predict MACEs in hypertensive patients who have undergone CCTA.

Association between mitral annulus calcification and subtypes of heart failure rehospitalization.

BACKGROUND: Mitral annulus calcification (MAC) has been associated with cardiovascular diseases, including heart failure (HF); however, the associations between MAC and both the category and etiology of HF have not been fully elucidated. The aim of this study was to investigate the relationship between MAC and three types of HF rehospitalization: HF with preserved ejection fraction (HFpEF), HF with mid-range EF (HFmrEF), and HF with reduced EF (HFrEF). METHODS: We enrolled consecutive patients undergoing echocardiography, who were admitted to our hospital for clinically indicated congestive HF between April 2014 and March 2018. Cox proportionalhazards models were used after adjusting for age, gender, and hypertension. RESULTS: Of 353 patients, 40 (11.3%) had MAC. With a median follow-up of 2.8 years, 100 (28%) patients were rehospitalized for congestive HF (HFpEF 40%, HFmrEF 16%, HFrEF 44%, respectively). According to the Kaplan-Meier method, the estimated incidence of HFpEF rehospitalization in the MAC group was significantly greater than that in the non-MAC group (p < 0.001) whereas the incidences of HFmrEF and HFrEF rehospitalization were comparable between the groups (p = 0.101 and p = 0.291, respectively). In a multivariate analysis, MAC remained significantly associated with HFpEF rehospitalization (hazard ratio: 3.379; 95% confidence interval: 1.651-6.597). At initial HF hospitalization, E/e' was significantly higher in the MAC group (both septum and lateral, p < 0.05), suggesting a possible relationship between MAC and left ventricular diastolic function. CONCLUSIONS: Mitral annulus calcification was associated with increased HFpEF rehospitalization and might be a cause of left ventricular diastolic dysfunction.

Association between major adverse cardiovascular events and pentraxin-3 in patients who have undergone coronary computed tomography angiography: from the FU-CCTA registry.

Chronic vasculitis is considered to be associated with future cardiovascular events. Here, we present major cardiovascular events (MACEs) in patients who underwent coronary computed tomography angiography (CCTA) for screening for coronary artery disease (CAD), and the association between MACEs and the inflammation marker pentraxin (PTX)-3 or highly sensitive C-reactive protein (hsCRP). The patients who underwent CCTA for the purpose of screening for CAD at Fukuoka University Hospital (FU-CCTA registry), 456 patients with suspected CAD or at least one cardiovascular risk factor were followed for up to 5 years. The levels of PTX-3 and hsCRP in blood were measured at the time of CCTA, and the patients were divided into two groups according to the presence (MACEs group) or absence (non-MACEs group) of MACEs. There were no differences in PTX-3 or hsCRP between the MACEs (-) and MACEs ( +) groups in all patients. A multivariate analysis related to the presence or absence of MACEs by logistic regression analysis of inflammation factors (PTX-3 and hsCRP) in addition to conventional risk factors as independent variables was performed. PTX-3 was a predictor of MACEs in males, whereas smoking, but not PTX-3, was a predictor of MACEs in females. PTX-3 could be a predictor of MACEs in males, but not females.

Adult influenza epidemic is associated with out-of-hospital cardiac arrest: From the All-Japan Utstein Registry, a prospective, nationwide, population-based, observational registry.

ABSTRACT: It has been reported that influenza infection is associated with out-of-hospital cardiac arrest of cardiac origin (OHCA-CA). However, the association between OHCA-CA and influenza epidemics in adults has not been well investigated.We analyzed data from the All-Japan Utstein Registry, a prospective, nationwide, population-based, observational study, regarding OHCA-CA cases and the Infectious Diseases Weekly Report for influenza cases: 17,710 OHCA-CA cases and 764,808 influenza cases were recorded between 2005 and 2015 in Fukuoka, Japan. The weekly average number of OHCA-CA cases was positively associated with the number of patients with influenza infection (r = 0.70, P < .0001). To eliminate the effects of season and age, we investigated only adults in winter. The weekly number of OHCA-CA cases was positively associated with the number of patients with influenza infection in weeks when there was a high frequency of influenza infection in adults (r = 0.36, P = .006), but not in weeks with a medium (r = 0.26, P = .05) or low frequency of influenza infection (r = 0.003, P = 1.0). In weeks during which there was a high frequency of influenza infection, the weekly number of OHCA-CA cases was positively associated with the number of influenza infections in males (r = 0.37, P = .006), but not females (r = 0.18, P = .2).The number of OHCA-CA cases was positively associated with the number of influenza infections in adult males during weeks in which there was a high frequency of influenza infections. To help prevent OHCA-CA in males, it might be beneficial to announce influenza epidemics specifically in adults, in addition to all ages.

Association Between Major Adverse Cardiovascular Events and the Ratio of Subcutaneous Fat Area to Visceral Fat Area in Patients Who Have Undergone Multidetector Row Computed Tomography.

Background: Obesity is a critical cardiovascular risk factor that has been defined in terms of body mass index (BMI), abdominal circumference (AC), and fat area. In this study, we examined which markers of obesity are most closely associated with major adverse cardiovascular events (MACE). Methods and Results: This prospective cohort study enrolled 529 consecutive patients who initially underwent coronary computed tomography angiography for screening of coronary atherosclerosis at Fukuoka University Hospital (FU-CCTA Registry) and either were clinically suspected of having coronary artery disease (CAD) or had at least 1 cardiovascular risk factor with a follow-up of up to 5 years. Measurements of subcutaneous fat area (SFA), visceral fat area (VFA), and AC were quantified using multidetector row computed tomography. The primary endpoint was MACE. SFA and the SFA to VFA ratio (SFA/VFA) were significantly lower in the MACE than non-MACE group. SFA, AC, BMI, and SFA/VFA were each independently associated with MACE. Receiver operating characteristic curve analysis revealed a greater area under the curve for SFA/VFA than for the other parameters. The cut-off level of SFA/VFA with the greatest sensitivity and specificity for the diagnosis of MACE was 1.45 (sensitivity 0.849, specificity 0.472). Conclusions: Our results suggest that SFA/VFA may be a marker for evaluating the presence of MACE.

Impact of Controlling a Nutritional Status Score on Wound Healing in Patients with Chronic Limb-Threatening Ischemia after Endovascular Treatment.

BACKGROUND: Chronic limb-threatening ischemia (CLTI) is the most advanced stage of peripheral artery disease. Therefore, a multidisciplinary approach is necessary to avoid major amputation in CLTI patients. Malnutrition worsens the condition of CLTI patients, and therefore, it may be important to evaluate the nutritional status in patients with CLTI. This study was designed to evaluate the baseline patient characteristics and the influence of the controlling nutritional status (CONUT) score on the clinical results. METHOD AND RESULTS: A retrospective, single-center, non-randomized study was conducted to evaluate the associations of death, major amputation, and wound healing rate at 12 months with the CONUT score on admission. Consecutive CLTI patients (mean age 73.2 ± 10.4 years; 84 males) who underwent endovascular therapy (EVT) for infra-popliteal lesions at Fukuoka University Hospital from January 2014 to May 2019 were enrolled and divided into two groups (higher and lower CONUT score groups). The higher CONUT group showed a higher percentage of dialysis (66.7% vs. 33.9%, p < 0.001) and a higher clinical frailty scale (5.9 ± 1.4 vs. 4.9 ± 1.9, p = 0.005) than the lower CONUT group. Rates of amputation-free survival were 89.5% and 69.8% in the lower and higher CONUT groups, respectively. In addition, rates of wound healing at 12 months were 98.0% and 78.3% in the lower and higher CONUT groups, respectively. Multivariate regression analysis demonstrated that a higher CONUT score was an independent predictor for delayed wound healing (OR: 11.2; 95% CI: 1.29-97.5; p = 0.028). CONCLUSION: An assessment of the nutritional status using the CONUT score could be useful for predicting wound healing, and earlier nutritional intervention may improve the outcome of CLTI patients. Early examination and treatment, along with raising awareness of the issue, may be important for improving the prognosis.

Endothelial lipase mediates efficient lipolysis of triglyceride-rich lipoproteins.

Triglyceride-rich lipoproteins (TRLs) are circulating reservoirs of fatty acids used as vital energy sources for peripheral tissues. Lipoprotein lipase (LPL) is a predominant enzyme mediating triglyceride (TG) lipolysis and TRL clearance to provide fatty acids to tissues in animals. Physiological and human genetic evidence support a primary role for LPL in hydrolyzing TRL TGs. We hypothesized that endothelial lipase (EL), another extracellular lipase that primarily hydrolyzes lipoprotein phospholipids may also contribute to TRL metabolism. To explore this, we studied the impact of genetic EL loss-of-function on TRL metabolism in humans and mice. Humans carrying a loss-of-function missense variant in LIPG, p.Asn396Ser (rs77960347), demonstrated elevated plasma TGs and elevated phospholipids in TRLs, among other lipoprotein classes. Mice with germline EL deficiency challenged with excess dietary TG through refeeding or a high-fat diet exhibited elevated TGs, delayed dietary TRL clearance, and impaired TRL TG lipolysis in vivo that was rescued by EL reconstitution in the liver. Lipidomic analyses of postprandial plasma from high-fat fed Lipg-/- mice demonstrated accumulation of phospholipids and TGs harboring long-chain polyunsaturated fatty acids (PUFAs), known substrates for EL lipolysis. In vitro and in vivo, EL and LPL together promoted greater TG lipolysis than either extracellular lipase alone. Our data positions EL as a key collaborator of LPL to mediate efficient lipolysis of TRLs in humans and mice.

Angiotensin Receptor Blocker and Neprilysin Inhibitor Suppresses Cardiac Dysfunction by Accelerating Myocardial Angiogenesis in Apolipoprotein E-Knockout Mice Fed a High-Fat Diet.

MATERIALS AND METHODS: Male apolipoprotein E-knockout mice fed a high-fat diet were divided into control (CTL), valsartan (30 mg/kg) (VAL), sacubitril (30 mg/kg) (SAC), and valsartan plus sacubitril (30 mg/kg each) (VAL/SAC) groups after 4 weeks of prefeeding and were subsequently treated for 12 weeks. RESULTS: The VAL/SAC group exhibited significantly higher serum brain natriuretic peptide levels; more subtle changes in left ventricular systolic diameter, fractional shortening, and ejection fraction, and significantly higher expression levels of natriuretic peptide precursor B and markers of angiogenesis, including clusters of differentiation 34, vascular endothelial growth factor A, and monocyte chemotactic protein 1, than the CTL group. CONCLUSIONS: Valsartan plus sacubitril preserved left ventricular systolic function in apolipoprotein E-knockout mice fed a high-fat diet. This result suggests that myocardial angiogenic factors induced by ARNI might provide cardioprotective effects.

Association between high-density lipoprotein cholesterol levels and major adverse cardiovascular events in patients who underwent coronary computed tomography angiography: FU-CCTA registry.

It is unclear whether higher levels of serum high-density lipoprotein cholesterol (HDL-C) prevent major adverse cardiovascular events (MACE). We prospectively evaluated 501 patients who had undergone coronary computed tomography angiography at Fukuoka University Hospital and either were clinically suspected of having coronary artery disease (CAD) or had at least one cardiovascular risk factor with a follow-up of up to 5 years. The primary endpoint was MACE (cardiovascular death, ischemic stroke, acute myocardial infarction and coronary revascularization). The patients were divided into tertiles according to the HDL-C level: 47 mg/dl ≥ HDL-C level [n = 167, lower HDL-C level (L-HDL)], 58 mg/dl ≥ HDL-C level ≥ 48 mg/dl [n = 167, middle HDL-C level (M-HDL)] and HDL-C level ≥ 59 mg/dl [n = 167, higher HDL-C level (H-HDL)] groups. There were significant differences in %CAD among the L-HDL, M-HDL and H-HDL groups. Unexpectedly, there was no difference in %MACE between M-HDL and H-HDL, although %MACE in M-HDL was significantly lower than that in L-HDL (p < 0.05). By a multivariate logistic regression analysis, MACE in H-HDL-C was independently associated with diabetes mellitus (DM) (p = 0.03). A Kaplan-Meier curve according to the HDL subgroup indicated that M-HDL, not H-HDL, enjoyed the greatest freedom from MACE among the 3 groups (log-rank test p = 0.047). Finally, the results of a Cox regression model indicated that L-HDL and H-HDL had significantly higher risk of MACE than M-HDL. In conclusions, patients with middle HDL-C levels, not higher HDL-C levels, showed the greatest freedom from MACE. Patients with higher HDL-C levels need to be strictly managed for DM to prevent MACE.

Combination of Linagliptin and Empagliflozin Preserves Cardiac Systolic Function in an Ischemia-Reperfusion Injury Mice With Diabetes Mellitus.

BACKGROUND: Sodium-glucose co-transporter 2 inhibitor (SGLT2i) and dipeptidyl peptidase 4 inhibitor (DPP4i) are oral hypoglycemic agents. Although SGLT2i has been shown having the beneficial effects on heart failure in basic and clinical studies, the combined effects of SGLT2i and DPP4i have not been established well. We investigated the effects of SGLT2i and DPP4i against diabetes mice model of myocardial ischemia-reperfusion injury. METHODS: Streptozotocin-induced diabetic C57BL/6J mice were divided into control (vehicle), empagliflozin (30 mg/kg/day), linagliptin (3 mg/kg/day) and combination (30 mg/kg/day and 3 mg/kg/day, respectively) groups. After 7 days of drug administration, 30 min of myocardial ischemia was performed. We investigated body weight, heart weight, blood glucose, and cardiac functions by pressure-volume Millar catheter followed by 28 days of additional drug administration. RESULTS: Blood glucose levels, body weight, and heart weight were not significantly different between the groups. In Millar catheter analysis, left ventricular volume at the peak left ventricular ejection rate which is one of the cardiac systolic parameters in combination group was significantly preserved than that in control (P = 0.036). The cardiac index in the combination group tended to be preserved compared to that in the control (P = 0.06). The pathological fibrotic area in the left ventricle in the combination group also tended to be smaller (P = 0.08). CONCLUSIONS: Combination therapy with linagliptin and empagliflozin preserved cardiac systolic function on the diabetes mice model of myocardial ischemia-reperfusion injury independent of blood glucose levels.

Association Between the Level of Low-Density Lipoprotein Cholesterol and Coronary Atherosclerosis in Patients Who Have Undergone Coronary Computed Tomography Angiography.

BACKGROUND: Although the Japan Atherosclerosis Society Guidelines 2017 recommend lower levels of low-density lipoprotein cholesterol (LDL-C, < 70 mg/dL or ≤ 100 mg/dL) to prevent secondary cardiovascular events, we cannot conclude that a low level of LDL-C prevents primary cardiovascular events in patients with suspected coronary artery disease (CAD). METHODS: We registered 1,016 patients who were clinically suspected to have CAD and who underwent coronary computed tomography angiography (CCTA) for screening of coronary atherosclerosis. We excluded 350 patients who were receiving anti-lipidemic therapies and finally analyzed 666 patients. The patients were divided into three groups according to the LDL-C level: < 70 mg/dL (n = 25, Low LDL-C), 70 - 99 mg/dL (n = 141, Middle LDL-C), and ≥ 100 mg/dL (n = 500, High LDL-C). A ≥ 50% coronary stenosis was initially diagnosed as CAD, and the number of significantly stenosed coronary vessels (VD), Gensini score and coronary artery calcification (CAC) score were quantified. RESULTS: There were no significant differences in age, high-density lipoprotein cholesterol, rates of hypertension, hemoglobin A1c, blood sugar or systolic blood pressure among the Low, Middle and High LDL-C groups. On the other hand, there were significant differences in rates of males, smoking, dyslipidemia and diabetes, diastolic blood pressure and triglyceride among the groups. The prevalence of CAD values in the Low, Middle and High LDL-C groups were similar, at 52%, 47%, and 46%, respectively. In addition, there were no significant differences in the number of VD, Gensini score or CAC score among the Low LDL-C, Middle LDL-C and High LDL-C groups. CONCLUSIONS: We showed that the level of LDL-C was not associated with the presence or severity of CAD, which indicates that we need to screen by CCTA to prevent primary coronary events even if patients without anti-lipidemic therapies show low levels of LDL-C.

Associations between smoking habits and major adverse cardiovascular events in patients who underwent coronary computed tomography angiography as screening for coronary artery disease.

We analyzed whether smoking was associated with major adverse cardiovascular events (MACE) and the progression of coronary atherosclerosis as assessed by coronary computed tomography angiography (CCTA) as screening for coronary artery disease (CAD). We enrolled 443 patients who had all undergone CCTA and either were clinically suspected of having CAD or had at least one cardiovascular risk factor. We divided the patients into smoking (past and current smoker) and non-smoking groups and into males and females, and evaluated the presence of CAD, severity of coronary atherosclerosis and MACE (cardiovascular death, ischemic stroke, acute myocardial infarction and coronary revascularization) with a follow-up of up to 5 years. %CAD and the severity of coronary atherosclerosis in the smoking group were significantly higher than those in the non-smoking group. %MACE in males and smokers were significantly higher than those in females and non-smokers, respectively. Interestingly, Kaplan-Meier curves also showed that female non-smokers enjoyed significantly greater freedom from MACE than female smokers (p = 0.007), whereas there was no significant difference in freedom from MACE between male non-smokers and male smokers (p = 0.984). Although there were no significant predictors of MACE in all patients according to a multiple logistic regression analysis, smoking was useful for predicting MACE in females, but not males. In conclusion, smoking was significantly associated with MACE in females, but not males, who underwent CCTA as screening for CAD.

Differences in lesion characteristics and patient background associated with the medium-term clinical outcomes of bare-metal and first-, second- and third-generation drug-eluting stents.

We investigated the lesion characteristics and patient background factors associated with the medium-term incidence of major adverse cardiac events (MACEs) for bare-metal stents (BMS) and 1st-, 2nd- and 3rd-generation drug-eluting stents (DES) using the PCI-Registry (FU-Registry). Between January 2003 and March 2016, 2967 cases/3508 lesions for which percutaneous coronary intervention was performed at Fukuoka University Hospital and related facilities were enrolled. Patients were divided into BMS and 1st-, 2nd- and 3rd-generation drug-eluting stent (DES) groups. The incidence of MACEs in the BMS group (26.2%) was significantly higher than those in the 1st, 2nd and 3rd DES groups (18.0%, 12.5%, and 11.0%, respectively). The incidence of MACEs in the BMS group was strongly associated with insulin use, hemodialysis, low high-density lipoprotein cholesterol, stent minimum lesion diameter, stent length, severe calcification and a small vessel diameter of less than 2.5 mm. Some of these factors showed no association with MACEs among the drug-elution groups, and only hemodialysis, arteriosclerosis obliterans and severe calcification showed a strong correlation in the 2nd DES group. In the 3rd DES group, none of the factors considered were associated with MACEs. In conclusion, in stent implantation, the number of factors associated with MACEs has gradually decreased as the stent generation increased.

Presence and severity of coronary artery disease in patients who achieved intensive blood pressure reduction at the time of coronary computed tomography angiography.

Blood pressure (BP)-lowering treatment should be aimed at achieving intensive BP control. Coronary computed tomography angiography (CCTA) has become more widely available and enables the accurate noninvasive assessment of coronary artery stenosis for screening. The presence and severity of coronary artery disease (CAD) in patients who achieved intensive BP control at the time of CCTA were compared to those in patients without hypertension (HTN). Nine hundred eighty-five consecutive subjects who were clinically suspected of having CAD or who had at least one cardiac risk factor underwent CCTA. The patients were divided into four groups: patients without HTN (non-HTN group), hypertensive patients who underwent intensive BP lowering (intensive group, <130/80 mmHg), patients who underwent standard BP lowering (standard group, 130-139/80-89 mmHg) and patients with uncontrolled BP (uncontrolled group, >140/90 mmHg). Interestingly, %CAD in the Intensive group was significantly higher than that in patients without HTN. The Intensive group was older and had a higher body mass index, more significantly stenosed coronary vessels, lower levels of high-density lipoprotein cholesterol in the blood, and higher rates of dyslipidemia, diabetes, and anti-dyslipidemia and anti-diabetic medication use than the non-HTN group. The presence of CAD in the Intensive group was independently associated with age, male and smoking, whereas the presence of CAD in the non-HTN group was associated with age, male and family history. Finally, predictors of the number of VDs in the non-HTN and intensive BP-lowering groups were age, male, DL, and intensive BP lowering. In conclusion, these results suggest that hypertensive patients need more rigorous management of other coronary risk factors, despite receiving intensive BP-lowering treatment.

Association between lipid profile and endothelial dysfunction as assessed by the reactive hyperemia index.

INTRODUCTION: We investigated the associations between endothelial dysfunction (ED) as evaluated by the reactive hyperemia index (RHI) obtained using Endo-PAT2000® and atherosclerotic risk factors in patients who underwent coronary artery angiography (CAG). METHODS: The subjects consisted of 191 patients who were clinically suspected to have CAD and underwent CAG, and in whom we could perform Endo-PAT2000®. We divided the patients into ED (RHI<1.67, n = 71) and non-ED (RHI≥1.67, n = 120) groups. RESULTS: The ED group was significantly older and showed a higher ratio of low-density lipoprotein cholesterol (LDL-C) to high-density lipoprotein cholesterol (HDL-C) (L/H) than the non-ED group. A multivariate logistic regression analysis was performed to examine the associations between the presence of ED and age, gender, and BMI in addition to L/H. Age [odds ratio (OR) = 1.03, p = .02] and L/H (OR = 1.64, p = .01) were identified as significant independent markers of the presence of ED. Next, we divided 122 patients with statin treatment into ED (n = 40) and non-ED (n = 82) groups. The ED group tended to have higher L/H and lower HDL-C than the non-ED group. HDL-C (OR = 0.95, p = .01) and age (OR = 1.05, p = .04) were identified as independent markers of the presence of ED. CONCLUSIONS: L/H was an independent marker of the presence of ED in patients without dyslipidemia. In addition, among patients with statin treatment, HDL-C was an independent marker of the presence of ED.