Significance of the percentage of cholesterol efflux capacity and total cholesterol efflux capacity in patients with or without coronary artery disease.

We hypothesized that cholesterol efflux capacity is more useful than the lipid profile as a marker of the presence and the severity of coronary artery disease (CAD). Therefore, we investigated the associations between the presence and the severity of CAD and both the percentage of cholesterol efflux capacity and total cholesterol efflux capacity and the lipid profile including the high-density lipoprotein cholesterol (HDL-C) level in patients who underwent coronary computed tomography angiography (CTA). The subjects consisted of 204 patients who were clinically suspected to have CAD and underwent CTA. We isolated HDL from plasma by ultracentrifugation and measured the percentage of cholesterol efflux capacity using 3H-cholesterol-labeled J774 macrophage cells and calculated total cholesterol efflux capacity as follows: the percentage of cholesterol efflux capacity/100× HDL-C levels. While the percentage of cholesterol efflux capacity was not associated with the presence or the severity of CAD, total cholesterol efflux capacity and HDL-C in patients with CAD were significantly lower than those in patients without CAD. In addition, total cholesterol efflux capacity and HDL-C, but not the percentage of cholesterol efflux capacity, significantly decreased as the number of coronary arteries with significant stenosis increased. Total cholesterol efflux capacity was positively correlated with HDL-C, whereas the percentage of cholesterol efflux capacity showed only weak association. In a logistic regression analysis, the presence of CAD was independently associated with total cholesterol efflux capacity, in addition to age and gender. Finally, a receiver-operating characteristic curve analysis indicated that the areas under the curves for total cholesterol efflux capacity and HDL-C were similar. In conclusion, the percentage of cholesterol efflux capacity using the fixed amount of isolated HDL was not associated with CAD. On the other hand, the calculated total cholesterol efflux capacity that was dependent of HDL-C levels had a significant correlation with the presence of CAD.

Effects of Tolvaptan With or Without the Pre-Administration of Renin-Angiotensin System Blockers in Hospitalized Patients With Acute Decompensated Heart Failure.

We examined whether tolvaptan combined with an angiotensin II receptor blocker (ARB) or angiotensin converting enzyme inhibitor (ACE-I) is more effective than tolvaptan alone in the treatment of patients with heart failure (HF). Sixty-five hospitalized patients with acute decompensated HF were included in this study. They were divided into 2 groups; an ARB/ACE-I group (n = 44, who received ARB or ACE-I before the use of tolvaptan) and a non-ARB/ACE-I group (n = 21). There were no significant differences in patient characteristics including medications at baseline between the non-ARB/ACE-I and ARB/ACE-I groups with the exception of the percentages of hypertension and ischemic heart disease. Urinary volume (UV) at baseline in the ARB/ACE-I group was slightly higher than that in the non-ARB/ACE-I group. The increase in UV after the use of tolvaptan in the non-ARB/ACE-I group was significantly higher than that in the ARB/ACE-I group. The cardiothoracic ratio and the reduction in body weight were similar between the groups after tolvaptan use. Finally, in a logistic regression analysis, a response to the use of tolvaptan was independently associated with the non-use of ARB/ACE-I, but not with age, gender, body mass index, loop diuretic, or human arterial natriuretic peptide. In conclusion, tolvaptan alone might induce an increase in UV in decompensated HF patients without ARB/ ACE-I, although the treatment of HF with ARB/ACE-I is the first choice strategy.

Comparison of Efficacy and Safety of Azilsartan and Olmesartan in Patients With Essential Hypertension.

Many patients still have high blood pressure (BP) after treatment with angiotensin II type 1 (AT1) receptor blockers (ARBs). We compared the efficacy and safety of azilsartan to those of olmesartan in a prospective randomized clinical trial. Sixty-four hypertensive patients who were treated with ARBs other than azilsartan and olmesartan were enrolled in this study. We randomly assigned patients to changeover from their prior ARBs to either azilsartan or olmesartan, and followed the patients for 3 months. Systolic BP (SBP) in the azilsartan group was significantly decreased at 3 months, and diastolic BP (DBP) and pulse rate (PR) in the olmesartan group showed significant reductions after 3 months. There were no significant differences in ΔSBP, ΔDBP, or ΔPR (Δ = the value at 3 months minus the value at 0 months) between the groups. Serum levels of creatinine (Cr), uric acid (UA), and potassium (K) in the azilsartan group significantly increased after 3 months. While the changes in Cr, UA, and K were within the respective normal ranges, ΔSBP was positively associated with ΔCr in the azilsartan group. In conclusion, there was no difference in the depressor effects of azilsartan and olmesartan, and there were no serious changes in biochemical parameters with azilsartan and olmesartan.

Association between smoking habits and severity of coronary stenosis as assessed by coronary computed tomography angiography.

Smoking promotes arteriosclerosis and is one of the most important coronary risk factors. However, few studies have investigated the association between smoking habits and the severity of coronary stenosis as assessed by coronary computed tomography angiography (CTA). We enrolled 416 patients [165/251 = smoker (past and current)/non-smoker)]. They had all undergone CTA and either were clinically suspected of having coronary artery disease (CAD) or had at least one cardiovascular risk factor. We divided the patients into smoking and non-smoking groups, and evaluated the presence of CAD, the number of significantly stenosed coronary vessels (VD), and the Gensini score as assessed by CTA in the two groups. The incidence of CAD, VD, the Gensini score, and coronary calcification score in the smoking group were all significantly greater than those in the non-smoking group (CAD, p = 0.009; VD, p = 0.003; Gensini score, p = 0.007; coronary calcification score, p = 0.01). Pack-year was significantly associated with VD and the Gensini score, and was strongly associated with multi-vessel disease (2- and 3-VD) (p < 0.05), whereas the duration of cessation in past smokers was not associated with VD or the Gensini score. Pack-year, but not the duration of cessation, may be the most important factor that was associated with the severity of coronary stenosis in terms of VD and the Gensini score.

Efficacy and safety of two single-pill fixed-dose combinations of angiotensin II receptor blockers/calcium channel blockers in hypertensive patients (EXAMINER study).

BACKGROUND: There is some controversy regarding which single-pill fixed-dose combinations of angiotensin II type 1 receptor blockers (ARBs) and calcium channel blockers (CCBs) are effective at reducing blood pressure (BP). METHODS: Sixty hypertensive patients who received a single-pill fixed-dose combination of valsartan 80 mg/day and amlodipine 5 mg/day were enrolled (UMIN Registration 000013460). They were randomly divided into two treatment groups [single-pill fixed-dose combination therapy with valsartan 80 mg/day and amlodipine 5 mg/day (Val/Am group), or irbesartan 100 mg/day and amlodipine 5 mg/day (Irb/Am group)] and treated for 16 weeks. If the patient did not reach the target office BP at 8 weeks, they received double doses of amlodipine (10 mg/day). RESULTS: In the Irb/Am group, systolic BP (SBP) and diastolic BP (DBP) were significantly decreased at 16 weeks. There were no significant changes in SBP or DBP in the Val/Am group. In the Irb/Am group, serum uric acid (UA) was significantly decreased at 8 weeks and patients who had hyperuricemia showed significantly decreased serum UA at 16 weeks. In addition, the levels of triglycerides (TG) were significantly decreased at 16 weeks in the Irb/Am group. CONCLUSION: A single-pill fixed-dose combination therapy with irbesartan 100 mg/day and amlodipine 5 mg/day was superior to the combination of valsartan 80 mg/day and amlodipine 5 mg/day with respect to significant decreases in BP, serum UA and TG in patients with hypertension.

Associations between parameters of flow-mediated vasodilatation obtained by continuous measurement approaches and the presence of coronary artery disease and the severity of coronary atherosclerosis.

We investigated the associations between the parameters of flow-mediated vasodilatation (FMD) obtained by continuous measurement approaches and the presence of coronary artery disease (CAD) and the severity of coronary atherosclerosis. The subjects consisted of 282 consecutive patients who underwent coronary angiography (CAG) and in whom we could measure FMD. Using continuous measurement approaches, we measured FMD as the magnitude of the percentage change from brachial artery diameter from baseline to peak (bFMD), the maximum FMD rate calculated as the maximal slope of dilation (FMD-MDR), and the integrated FMD response calculated as the area under the dilation curve during the 60- and 120 s dilation periods (FMD-AUC60 and FMD-AUC120). We divided the patients into two groups, the CAD group and the non-CAD group, and defined the severity of coronary atherosclerosis according to the Gensini score. The CAD group showed significantly lower %FMD, FMD-MDR, FMD-AUC60, and FMD-AUC120. Gender, smoking, dyslipidemia (DL), and diabetes mellitus (DM), in addition to FMD-AUC120, were identified as significant independent variables that predicted the presence of CAD by a multivariate logistic regression. In addition, a multiple regression analysis indicated that gender, DL, and hypertension, in addition to FMD-AUC120, were predictors of the Gensini score. Finally, we defined the cutoff value of FMD-AUC120 for the prediction of CAD in all patients as 11.1 (sensitivity 0.582, specificity 0.652) by a receiver-operating characteristic (ROC) curve analysis. In conclusion, FMD-AUC120 as assessed by continuous measurement approaches may be a superior marker for evaluating the presence of CAD and the severity of coronary atherosclerosis.

Association between the severity of coronary artery stenosis and the combination of the difference in blood pressure between arms and brachial-ankle pulse wave velocity.

BACKGROUND: A difference in systolic blood pressure (SBP) ≥10 mmHg between the arms is associated with an increased risk of coronary artery disease (CAD) and mortality in high-risk patients. METHODS AND RESULTS: Four hundred and fourteen patients were divided into three groups according to the percent most severe luminal narrowing of a coronary artery as diagnosed by coronary computed tomography angiography: no or mild coronary stenosis (0-49%), moderate stenosis (50-69%) and severe stenosis (≥70%) groups. The relative difference in SBP between arms in the severe group was significantly lower than those in the no or mild and moderate groups. The brachial-ankle pulse wave velocity (baPWV) significantly increased as the severity of coronary stenosis increased. We confirmed that severe coronary stenosis was independently associated with both the relative difference in SBP between arms and baPWV, in addition to age, gender, hypertension, dyslipidemia, diabetes mellitus and ankle-brachial index by a logistic regression analysis. The group with a relative difference in SBP between arms of <1 mmHg and baPWV ≥ 1613 cm/s showed a higher percentage of patients with severe coronary stenosis than groups that met neither or only one of these criteria. CONCLUSION: The combination of the relative difference in SBP between arms and baPWV may be a more effective approach for the non-invasive assessment of the severity of CAD.

Inappropriate direct oral anticoagulant dosing in atrial fibrillation patients is associated with prescriptions for outpatients rather than inpatients: a single-center retrospective cohort study.

BACKGROUND: Inappropriate dosing of direct oral anticoagulants (DOACs) has been associated with clinical safety and efficacy; however, little is known about clinical data associated with an inappropriate DOAC dosing in Japan. In addition, there is no report in which the appropriateness of DOAC dosing between prescription for inpatients and for outpatients was examined. In this study, we aimed to investigate the prevalence and factors associated in the inappropriate dosing of DOACs in patients with atrial fibrillation (AF). METHODS: The retrospective cohort study was conducted at a single Japanese university hospital. Both inpatients and outpatients, who were diagnosed with AF and for whom treatment with either dabigatran, rivaroxaban, apixaban, or edoxaban was initiated between April 1, 2014 and March 31, 2018, were enrolled in the study. Appropriateness of DOAC dosing was assessed according to the manufacturer's labeling recommendations (dose reduction criteria) of each DOAC. Inappropriate reduced dose, namely, underdosing, was defined as prescription of a reduced dose of DOAC despite the patient not meeting the dose reduction criteria. Inappropriate standard dose, namely, overdosing, was defined as prescription of a standard dose of DOAC despite the patient meeting the dose reduction criteria. Inappropriate DOAC dosing was defined as a deviation of the recommended dose (both underdosing and overdosing). RESULTS: A total of 316 patients (dabigatran, 28; rivaroxaban, 107; apixaban, 116; and edoxaban, 65) were included, with a median (interquartile range) age of 75 (66-81) years and 62.3% male. DOACs were prescribed at an appropriate standard dose in 39.2% of patients, an appropriate reduced dose in 36.7%, an inappropriate standard dose in 2.5%, and an inappropriate reduced dose in 19.3%. Multivariate analysis revealed that the inappropriate dosing of DOACs was significantly associated with prescriptions for outpatients (vs. inpatients; odds ratio [OR] 2.87, 95% confidence interval [CI] 1.53-5.62, p < 0.001) and those with higher HAS-BLED scores (OR 1.87, 95% CI 1.42-2.51, p < 0.001). CONCLUSIONS: Our results demonstrated that the inappropriate dosing of DOACs occurred in approximately 20% of AF patients, and was more frequent in outpatients (vs. inpatients) and in those with a higher risk of bleeding. It is recommended that pharmacists play a greater role in assisting in the prescription process to help physicians make better decisions.

Depressor and Anti-Inflammatory Effects of Angiotensin II Receptor Blockers in Metabolic and/or Hypertensive Patients With Coronary Artery Disease: A Randomized, Prospective Study (DIAMOND Study).

BACKGROUND: We compared the efficacy and safety of azilsartan to those of olmesartan in a prospective, randomized clinical trial. METHODS: Forty-four hypertensive patients who had coronary artery disease (CAD) were enrolled. We randomly assigned patients to changeover from their prior angiotensin II receptor blockers (ARBs) to either azilsartan or olmesartan, and followed the patients for 12 weeks. RESULTS: Office systolic blood pressure (SBP) in the azilsartan group was significantly decreased after 12 weeks. SBP and diastolic blood pressure (DBP) after 12 weeks in the azilsartan group were significantly lower than those in the olmesartan group. The percentage of patients who reached the target BP at 12 weeks (78%) in the azilsartan group was significantly higher than that at 12 weeks (45%) in the olmesartan group. There were no significant changes in pentraxin-3, high-sensitively C-reactive protein or adiponectin in blood after 12 weeks in either group. Although serum levels of creatinine (Cr) in the azilsartan group significantly increased, these changes were within the respective normal range. CONCLUSION: In conclusion, the ability of azilsartan to reduce BP may be superior to that of prior ARBs with equivalent safety in hypertensive patients with CAD.

Visit-to-Visit Variability and Seasonal Variation in Blood Pressure With Single-Pill Fixed-Dose Combinations of Angiotensin II Receptor Blocker/Calcium Channel Blocker and Angiotensin II Receptor Blocker/Diuretic in Hypertensive Patients.

BACKGROUND: The visit-to-visit variability in blood pressure (BP) has been shown to be a strong predictor of cardiovascular events. It is not known whether anti-hypertensive therapy using a single-pill fixed-dose combination of angiotensin II receptor blocker (ARB)/calcium channel blocker (CCB) or ARB/diuretic (DI) in hypertensive patients affects the visit-to-visit variability and seasonal variation of BP. METHODS: We enrolled 47 hypertensive patients who had received a single-pill fixed-dose combination of either ARB/CCB (n = 30) or ARB/DI (n = 17) for 15 months. Beginning 3 months after the start of ARB/CCB or ARB/DI treatment, we determined the visit-to-visit variability in BP expressed as the standard deviation (SD) of average BP and the seasonal variation in BP expressed as the SD of average BP in each season (spring, summer, fall and winter were defined as lasting from March to May, June to August, September to November and December to February, respectively) for a year. RESULTS: There were no significant differences in baseline patient characteristics except for the prevalence of coronary artery disease and the percentage of CCB excluding amlodipine in the ARB/CCB group between the ARB/CCB and ARB/DI groups. There were no significant differences in the 1-year time course of systolic and diastolic BP (SBP and DBP) between the groups, although there were significant differences in SBP in August and November and DBP in December. Interestingly, the visit-to-visit variability and seasonal variation of BP in the ARB/CCB group were similar to those in the ARB/DI group. CONCLUSION: Single-pill fixed-dose combinations of ARB/CCB and ARB/DI had similar effects on visit-to-visit variability and seasonal variation in BP in hypertensive patients.

Impact of the Absolute Difference in Diastolic Blood Pressure Between Arms in Patients With Coronary Artery Disease.

BACKGROUND: We investigated the relationship between the severity and presence of coronary artery disease (CAD) and a difference in systolic and diastolic blood pressure (SBP and DBP) between arms or between lower limbs. METHODS: We enrolled 277 patients who underwent coronary angiography. We calculated the absolute (|right BP (rt. BP) - left BP (lt. BP)|) and relative (rt. BP - lt. BP) differences in SBP or DBP between arms or between lower limbs, and assessed the severity of CAD in terms of the Gensini score. RESULTS: The absolute difference in DBP between arms in the CAD group was significantly lower than that in the non-CAD group, whereas the absolute difference in DBP between lower limbs in the CAD group was significantly higher. There were no differences in the absolute or relative difference in SBP between arms or lower limbs between the groups. The absolute difference in DBP between arms decreased as the Gensini score increased. In a logistic regression analysis, the presence of CAD was independently associated with the absolute difference in DBP between arms, in addition to male, family history, dyslipidemia, diabetes mellitus and hypertension. CONCLUSION: The absolute difference in DBP between arms in addition to traditional factors may be a critical risk factor for the presence of CAD.

Ratio of eicosapentaenoic acid to arachidonic acid is a critical risk factor for acute coronary syndrome in middle-aged older patients as well as younger adult patients.

BACKGROUND: Coronary risk factors for the onset of acute coronary syndrome (ACS), including polyunsaturated fatty acids (PUFAs), in younger adult patients may be different from those in older patients. METHODS AND RESULTS: We enrolled 578 patients who underwent coronary angiography at Fukuoka Saiseikai Hospital, and divided them into a younger adult group (YG) (<50 years, n=47) and a middle-aged older group (OG) (≥50 years, n=531). In a multivariate analysis, lower levels of high-density lipoprotein cholesterol and the ratio of eicosapentaenoic acid (EPA) to arachidonic acid (AA) (EPA/AA), and less aspirin, oral hypoglycemic agent, and calcium channel blocker (CCB) use were independent risk factors for ACS in all patients. In YG, lower levels of EPA/AA and less angiotensin II receptor blocker/angiotensin-converting enzyme inhibitor use were the independent risk factors. In OG, smoking, lower levels of EPA/AA, less aspirin and CCB use were the risk factors. While lower levels of EPA/AA was the only risk factor for ACS that was common to all patients, YG and OG, docosahexaenoic acid/AA was not associated with ACS in YG and OG. CONCLUSIONS: Lower level of EPA/AA is a common critical risk factor for ACS in middle-aged older patients as well as younger adult patients. Some of the risk factors for the onset of ACS in younger patients were different from those in older patients.