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 paroxysmal or persistent atrial fibrillation and hyperuricemia in patients who underwent coronary computed tomography angiography: from the FU-CCTA-AF Registry.

BACKGROUND: Hyperuricemia (HU) and hypertension (HTN) contribute to atherosclerotic cardiovascular disease, and both are also involved in the onset and development of atrial fibrillation (AF). OBJECTIVE: In the present study, we investigated the association between risk factors for atherosclerosis [including HU, HTN, blood pressure and serum uric acid (UA) levels] and paroxysmal atrial fibrillation (Paro-AF) or persistent atrial fibrillation (Pers-AF) in patients who underwent coronary computed tomography angiography (CCTA). METHODS: We enrolled 263 patients from the Fukuoka University-CCTA-AF (FU-CCTA-AF Registry) who underwent CCTA prior to AF ablation therapy. AF was classified as either Paro-AF (≤ 7 days) or Pers-AF (> 7 days). HU was diagnosed by a serum UA level > 7.0 mg/dl, and coronary artery disease (CAD) was diagnosed when CCTA results showed ≥ 50% significant coronary artery stenosis. The number of significantly diseased coronary artery vessels (VD), the Gensini score and the coronary artery calcification score (CACS) were measured. Left atrial morphology was also evaluated. RESULTS: Diastolic blood pressure and HbA1c in the Pers-AF group were significantly higher than those in the Paro-AF group. The Pers-AF group showed a significantly higher prevalence of HU and higher UA levels than the Paro-AF group. In a multivariate logistic regression analysis, HU was an independent associated factor to Pers-AF (odds ratio: 2.023, 95% confidence interval: 1.055-3.881, p = 0.034), while HTN was not. CONCLUSION: In patients with AF, HU is associated with Pers-AF.

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.

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.

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.

Association between plasma levels of PCSK9 and the presence of coronary artery disease in Japanese.

The ability of pro-protein convertase subtilisin/kexin type 9 (PCSK9) levels to predict the presence or severity of coronary artery disease (CAD) remains controversial. The purpose of this study was to investigate these associations. We enrolled 393 patients who were clinically suspected to have CAD or who had at least one cardiac risk factor and underwent multidetector-row computed tomography coronary angiography. The presence of CAD (≥50% coronary stenosis), the number of significantly stenosed coronary vessels, and plasma levels of PCSK9 by ELISA were analyzed. Plasma PCSK9 levels (log-transformed data) were significantly associated with the presence of CAD. Next, we divided the patients into two groups (non-statin and statin groups) according to statin treatment. PCSK9 levels in the non-statin group were significantly lower than those in the statin group. There were no significant differences in PCSK9 levels between the absence and presence of CAD in the statin group. However, in the non-statin group, PCSK9 levels in patients with CAD were significantly higher than those in patients without CAD. PCSK9 levels, in addition to age, gender, BMI, DM and HDL-C, were independently associated with the presence of CAD by a multivariable analysis. In conclusion, our results demonstrated that plasma PCSK9 levels may be a marker for evaluating the presence of CAD.

Correction to: Association between plasma levels of PCSK9 and the presence of coronary artery disease in Japanese.

In the original publication of the article, Tables 1, 2 and 3 was published incorrectly. Unnecessary inequality symbols were added to all the numbers in the 'p value' of Tables 1, 2 and 3. The correct tables should be as follows.

Unique mode of binding between angiotensin II type 1 receptor and its blockers.

BACKGROUND: We hypothesized that the 5-oxo-1,2,4-oxadiazole moiety of azilsartan (AZL), which represents a small difference in the molecular structures of AZL and candesartan (CAN) [angiotensin II type 1 receptor (AT1R) blockers], may be responsible for the molecular effects of AZL. METHODS: We examined the binding affinities of AZL and CAN to AT1R, along with their ability to block receptor activity. A competition binding study, inositol phosphate (IP) production assay and extracellular signal-regulated kinase (ERK) assay were performed using wild-type (WT) and mutants AT1R-transfected cells. RESULTS: The binding affinities of CAN and AZL were reduced by > 5-fold for Y35F, W84F, R167K, K199Q and I288A compared with WT. In addition, AZL showed a > 5-fold reduction in its binding affinity to V108A. CAN and AZL exhibited > 20-fold and > 100-fold reductions in binding affinity to R167K, respectively. The loss of binding affinity of AZL to R167K was greater than that of CAN. CAN-7H exhibited a > 10-fold reduction in binding affinity to R167K compared with CAN. On the other hand, the binding affinity of AZL-7H to R167K was comparable to that of AZL. While 10-6M CAN and CAN-7H partly blocked Ang II-induced IP production in R167K, 10-6M AZL and AZL-7H did not. In addition, 10-6M CAN, but not 10-6M AZL, partly blocked Ang II-induced ERK activation in R167K. CONCLUSIONS: The interaction between 5-oxo-1,2,4-oxadiazole in AZL and Arg167 in the AT1R appears to be more important than the interaction between the tetrazole ring in CAN and Arg167.

Association Between the Presence or Severity of Coronary Artery Disease and Pericardial Fat, Paracardial Fat, Epicardial Fat, Visceral Fat, and Subcutaneous Fat as Assessed by Multi-Detector Row Computed Tomography.

The associations between the presence or severity of coronary artery disease (CAD) and measurements of various kinds of fat as assessed by multidetector row computed tomography (MDCT) are unclear. We enrolled 300 patients who were clinically suspected to have CAD or who had at least one cardiac risk factor and had undergone MDCT. The number of significantly stenosed coronary vessels (VD), and measurements of pericardial fat index, paracardial fat index, epicardial fat index, visceral fat index, and subcutaneous fat index were quantified using MDCT. Plasma levels of adiponectin, pentaxin-3, and high-sensitivity C-reactive protein factors were also measured. Pericardial fat index, paracardial fat index, and visceral fat index in a CAD group were significantly greater than those in a non-CAD group. In addition, the levels of these fat indices tended to increase as the number of VD increased and were positively correlated with the Gensini score. The area-under-the-curve for paracardial fat index was significantly greater than those for the other parameters of fat index measured by a receiver-operating characteristic curve analysis. The cut-off level of paracardial fat index that gave the greatest sensitivity and specificity for the diagnosis of CAD was 54.9 cm3/m2 (sensitivity 0.710, specificity 0.552). The presence of CAD was independently associated with paracardial fat index, in addition to age and diabetes mellitus, by a multiple logistic regression analysis. In conclusion, paracardial fat index may be a marker for evaluating the presence or severity of CAD.

Considering the Possible Role of Pharmacists According to the Presence or Absence of Lifestyle-Related Diseases at the Time of Coronary CT Examination and Trends of Medication Use for These Diseases by Medical Doctors.

BACKGROUND: Because patients often already have coronary artery disease (CAD) at the time of a coronary artery computed tomography angiography (CCTA) examination, we examined the medications prescribed by medical doctors for lifestyle-related diseases and investigated what possible role pharmacists can play in prescribing. METHODS: Patients (n = 1357) who underwent CCTA examination were divided into two groups according to the presence or absence of lifestyle-related diseases [hypertension (HTN), dyslipidemia (DL) and diabetes mellitus (DM)], and the relationship between the presence or absence of CAD was examined. RESULTS: The rate of CAD was significantly higher in patients with HTN, DL or DM than in patients without these diseases. The blood pressure in the HTN group was 140 ± 20/79 ± 13 mmHg, the low-density lipoprotein cholesterol value in the DL group was 119 ± 35 mg/dL, and the hemoglobin A1c value in the DM group was 7.0 ± 1.1%, all of which were poorly controlled. Anti-hypertensive drugs were used at low rates in the HTN group, statins were used in 47% and ezetimibe was used in 4% of the DL group, and dipeptidyl peptidase-4 inhibitors were used in 41% of the DM group. CONCLUSIONS: Since the rate of CAD (+) was high and control of the three major lifestyle-related diseases was poor, pharmacists should advise medical doctors to use combinations of drugs.

Association Between Major Adverse Cardiovascular Events and Left Ventricular Mass Index in Patients Who Have Undergone Coronary Computed Tomography Angiography: From the FU-CCTA Registry.

Background: Left ventricular mass (LVM) is a predictor of future cardiovascular risk. We determined the association between LVM measured by coronary computed tomography angiography (CCTA) and the prognosis in patients who have undergone CCTA for screening of coronary artery disease (CAD). Methods: We performed a prospective cohort study. Five hundred twenty consecutive patients who underwent CCTA at Fukuoka University Hospital (FU-CCTA registry) were enrolled. They were clinically suspected of having CAD or had at least one cardiovascular risk factor, and were a follow-up of up to 5 years. Equal to more than 50% of coronary stenosis as assessed by CCTA was diagnosed as CAD. Using CCTA, LVM index (LVMI), LV ejection fraction (LVEF), LV end-diastolic volume (LVEDV) and LV end-systolic volume were measured. The primary endpoint was major adverse cardiovascular events (MACEs: including all causes of death, ischemic stroke, acute myocardial infarction and coronary revascularization). The patients were divided into non-MACEs and MACEs groups. Results: The non-MACEs and MACEs groups consisted of 478 and 42 patients, respectively. Percent of CAD in the MACEs group was significantly higher than that in the non-MACEs group. The MACEs group showed significantly higher LVMI and tended to have a lower LVEF and LVEDV than the non-MACEs group. Although LVMI was not associated with MACEs in all patients, LVMI was independently associated with MACEs in males (odd ratio: 1.018, 95% confidence interval: 1.002 - 1.035, P = 0.030), but not females. Conclusions: Evaluation of LVMI by CCTA may be useful for predicting MACEs in males.

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 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 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.

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.

Angiographic findings and treatment of coronary sinus spasm during left ventricular lead placement: A case report.

A 71-year-old man with ischemic cardiomyopathy, a left ventricular (LV) ejection fraction of 23 %, left bundle branch block with a QRS duration of 160 milliseconds, and nonsustained ventricular tachycardia was admitted for cardiac resynchronization therapy combined with an implantable defibrillator. During LV lead placement, the guiding sheath encountered strong resistance during deep coronary sinus (CS) cannulation. CS venography showed a complete occlusion, and we diagnosed venospasm because the occlusion self-resolved after several minutes. After administering intravenous isosorbide dinitrate and waiting several minutes without manipulating the catheters, we could successfully place the LV lead in the target branch. Although CS spasm is considered a rare complication of LV lead placement, in some cases catheter manipulation can trigger it. Therefore, clinicians should recognize its possibility and be aware of the associated angiographic findings and treatment. Learning objective: In some cases, coronary sinus (CS) spasm can be triggered during left ventricular lead placement. It presents as occlusion with abrupt tapering on CS venography. After administering intravenous nitrates and waiting several minutes without manipulating the catheters, the spasm resolves and the catheter can be advanced.

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.

Associations between High-Density Lipoprotein Functionality and Major Adverse Cardiovascular Events in Patients Who Have Undergone Coronary Computed Tomography Angiography.

The present study aimed to investigate the associations between high-density lipoprotein (HDL) functionality and major adverse cardiovascular events (MACE) in patients who have undergone coronary computed tomography angiography (CCTA). We performed a prospective cohort study and enrolled 151 patients who underwent CCTA and had a follow-up of up to 5 years. We measured cholesterol efflux capacity (CEC), caspase-3/7 activity and monocyte chemoattractant protein-1 (MCP-1) secretion as bioassays of HDL functionality. The patients were divided into MACE(-) (n = 138) and MACE(+) (n = 13) groups. While there was no significant difference in %CEC, caspase-3/7 activity or MCP-1 secretion between the MACE(-) and MACE(+) groups, total CEC and HDL cholesterol (HDL-C) in the MACE(+) group were significantly lower than those in the MACE(-) group. Total CEC was correlated with HDL-C. A receiver-operating characteristic curve analysis showed that there was no significant difference between the areas under the curves for total CEC and HDL-C. In conclusion, total CEC in addition to HDL-C, but not %CEC, was associated with the presence of MACE. On the other hand, HDL functionality with regard to anti-inflammatory and anti-apoptosis effects was not associated with MACE.

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.

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.