Tokushi Koga

Ageing suppresses endothelium-dependent relaxation and generates contraction mediated by the muscarinic receptors in vascular smooth muscle of normotensive Wistar-Kyoto and spontaneously hypertensive rats.

We evaluated the effects of ageing and hypertension on endothelium-dependent relaxation and contraction of vascular smooth muscles. Aortic rings with and without endothelium from normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR), divided into young, adult and old groups, were examined for relaxation in response to acetylcholine, adenosine triphosphate (ATP) and sodium nitroprusside. Relaxation responses to acetylcholine and ATP in SHR were either equal to or greater than those in WKY. Relaxations induced by ATP were not altered by ageing, while the degree of acetylcholine-induced endothelium-dependent relaxations was in an inverse order of age in both SHR and WKY. In old SHR and WKY and adult SHR, lower doses of acetylcholine caused relaxations, but increases in the dose of acetylcholine induced contraction. Acetylcholine-induced contractions were abolished by indomethacin or endothelium rubbing. We conclude that endothelium-dependent relaxations are not diminished by spontaneous hypertension but the relaxations mediated by the muscarinic receptors are reduced with ageing. Further, acetylcholine causes endothelium-dependent contractions by releasing cyclo-oxygenase products, not only in SHR but also in aged normotensive WKY.

Neurally-Mediated Syncope Induced by Lung Cancer A Case Report

The authors present hemodynamic and autonomic features of recurrent and episodic neurally-mediated syncope in a man with lung cancer involving afferent vagus. He revealed extreme hypotension with bradycardia occurring during sitting or standing. A head-up tilt test also induced syncope. However, syncope attacks no longer occurred 2 weeks after admission. Alternatively, the paralyses of the left recurrent laryngeal nerve and the left phrenic nerve developed. It is suggested that the lung cancer involved upper rootlets of the left vagus and caused transient hypersensitivity of baroreceptor function that resulted in neurally-mediated syncope.

Circumferential spontaneous coronary artery dissection in an elderly man : A case report

An 82-year-old man developed acute inferior myocardial infarction. Emergent coronary angiography demonstrated thrombotic occlusion in the right coronary artery. Intracoronary thrombolytic therapy was performed with successful recanalization. However, circumferential dissection with luminal stenosis was revealed at the point of thrombus formation. Repeat angiography 6 months later showed resolution of the dissec tion. This is the first description of circumferential spontaneous coronary artery dissec tion. In addition, the present patient is older than any previous patients.

Pharmacokinetics of quinapril in patients with renal dysfunction

Abstract The pharmacokinetic properties of quinapril were evaluated in 6 hypertensive patients with normal renal function (group A), 4 hypertensive patients with mild-to-moderate renal dysfunction (group B), and 3 hypertensive patients with severe renal dysfunction (group C). Assessments were made after patients received a single oral 10-mg dose of quinapril and after they received 8 consecutive days of treatment. The peak drug level and the area under the curve for quinaprilat (the active metabolite of quinapril) were 2 to 4 times higher in group C than in group A after 8 days of treatment; this difference was statistically significant. A significant correlation between the area under the curve and serum creatinine levels was observed after the single dose and after 8 days of treatment. Based on our results, we recommend that patients with renal dysfunction receive only half the dose of quinapril administered to patients with normal renal function.

Correlation between increased urinary sodium excretion and decreased left ventricular diastolic function in patients with type 2 diabetes mellitus

Increased salt intake may induce hypertension, lead to cardiac hypertrophy, and exacerbate heart failure. When elderly patients develop heart failure, diastolic dysfunction is often observed, although the ejection fraction has decreased. Diabetes mellitus (DM) is an established risk factor for heart failure. However, little is known about the relationship between cardiac function and urinary sodium excretion (U‐Na) in patients with DM.

Low diastolic blood pressure was one of the independent predictors of ischemia-like findings of electrocardiogram in patients who underwent coronary angiography

BACKGROUND The underlying cause of a high cardiovascular event rate in the population with low diastolic blood pressure (DBP) has not been fully elucidated. METHODS AND RESULTS The relationship between DBP and ischemia-like findings on electrocardiography (ECG) was investigated in 187 patients who underwent coronary angiography. Patients with conditions affecting ECG (e.g. patients taking digitalis or those with old myocardial infarction, complete right bundle branch block, or hypokalemia) were excluded from the analyses. Ischemia-like ECG was defined as having one or more of the following: borderline Q wave [Minnesota code (MC) I 3], ST depression (MC IV 1-3), negative T wave (MC V 1-3), and complete left bundle branch block (MC VII 1). Based on this definition, 70 of 187 patients (37%) had ischemia-like ECG. Compared with the group without it, the group with ischemia-like ECG included more females (p<0.01), and had lower values of body mass index (p = 0.01), DBP (p<0.01), estimated glomerular filtration rate (p<0.01), left ventricular ejection fraction (LVEF; p<0.01), and higher values of age (p<0.01) and left ventricular mass index (LVMI; p<0.01). The severity of coronary artery disease did not differ between the groups. Receiver operating characteristics curve analysis revealed that 74.5 mmHg was the optimal cut-off point of DBP to predict ischemia-like ECG (area under curve, 0.63; 95% confidence interval, 0.55-0.71, p = 0.003). There were no significant relationships between systolic blood pressure and ischemia-like ECG. A multivariate analysis showed that female sex, low DBP (≤ 74.5 mmHg), LVMI, and LVEF were the significant factors for the ischemia-like ECG. The odds ratio of low DBP was 2.53 (95% confidence interval, 1.19-5.40; p = 0.02). CONCLUSIONS Low DBP was one of the significant predictors of the ischemia-like ECG in the present study. Myocardial ischemia may be a part of the cause of high cardiovascular morbidity in the population with low DBP.

BOTH HIGH AND LOW SUPINE BLOOD PRESSURE AS WELL AS ITS POSTURAL FALL ARE INDEPENDENT RISK FACTORS FOR THE PROGNOSIS IN PATIENTS WITH HEART FAILURE

Objective: Orthostatic hypotension has been reported to be a risk factor for worsening heart failure (HF). The authors investigated prognostic values of blood pressure (BP) in the supine, sitting and standing positions, and those of postural variation of BP, in patients with HF. Design and method: Seventy-six consecutive cases (age, 81 ± 9y; male, 53%) who admitted to our hospital for HF and discharged after cardiac rehabilitation during a period from Jul 2014 to Jan 2016 were studied. Patients with atrial fibrillation, or who could not keep standing for 2 minutes at discharge, were not included. The left ventricular ejection fraction (LVEF) was preserved (40% or more) in 61 cases (80%). BPs were measured in the supine and sitting positions, and 1-min and 2-min after standing just before the discharges. The relationships among composite events (admission due to cardiovascular disease and all cause death) and demographic factors including BP and BP variation were investigated. Results: Over a median follow-up of 10.9 months, 26 composite events (readmission due to HF, 21; angina, 1; all-cause death, 4) occurred. Among subgroups of supine systolic BP (SBP) categories, the 1st quintile (77∼108mmHg) and the 4th+5th quintiles (126∼169mmHg) had increased risks of the composite events, compared with the 2nd+3rd quintiles (109∼125mmHg) (p < 0.01). On the other hand, there were no significant differences in the events rate among the subgroups of sitting or standing SBP categories. Among the subgroups of &dgr;SBP from the sitting position to 1-min standing, the 1st+2nd quintiles (−60∼-12mmHg) had more events than the 3rd+4th+5th quintiles (−11∼+30mmHg) did (p < 0.01). There was no significant association between &dgr;SBP from the supine to sitting position and prognosis. In a multivariate analysis, supine SBP, &dgr;SBP from the sitting positon to 1-min standing, and eGFR were significant prognostic factors. Conclusions: Both supine SBP and &dgr;SBP from the sitting to 1-min standing had independent prognostic values in patients with HF: they might reflect different mechanisms of worsening HF.

PS 14-12 CLINICAL SIGNIFICANCE OF AMBULATORY BLOOD PRESSURE MONITORING IN PATIENTS WITH CARDIOVASCULAR DISEASES WHO UNDERWENT CARDIAC REHABILITATION

Objective: Though optimal blood pressure (BP) control is crucial in the treatment of patients with cardiovascular diseases (CVDs), the usefulness of ambulatory BP monitoring (ABPM) in cardiac rehabilitation remains unclear. The aim of the present study was to investigate the association between BP evaluated by ABPM and adverse symptoms or events in patients who underwent cardiac rehabilitation. Design and Method: Sixty patients (mean age; 80 ± 10 years, mean ± s.d. female; 51.7%, heart failure as a cause of index hospitalization, 72%) who could walk by themselves were studied BP levels, circadian rhythm using ABPM before discharge, symptoms due to hypotension from clinical records during admission, and they were followed up until a year after. Results: Among the subjects, mean 24-hour BP was 128 ± 18/72 ± 8 mmHg on 2.6 ± 1.3 anti-hypertensive drugs, and the majority of them represented non-dipper (48%) or riser (33%) pattern. When the subjects were categorized into the low, medium, and high BP group based on the tertiles of the mean 24-hour systolic BP (SBP), the prevalence of hypotensive symptoms were 5%, 5%, and 10% respectively. During the follow-up period (median, 375 days), 23 composite adverse events occurred. The prevalence of the composite events was highest in the high BP group, and there was a significant difference among the event-free survival curves of these three groups (p < 0.01) by Kaplan–Meier method and log-rank test. The adjusted relative hazard ratio of mean 24-hour SBP for the composite events was 9.32 (95%CI; 1.13–81.2, p < 0.01) with a 1 s.d. increment by Cox proportional hazard model. There was no significant difference in the prevalence of hypotensive symptoms or the composite adverse events among circadian rhythms. Conclusions: These results suggest that mean value of 24-hour BP was associated with the adverse events in patients who underwent rehabilitation for CVDs. There were no significant relations among BP levels, circadian rhythms, and hypotensive symptoms.

PS 14-20 THE RELATIONSHIP BETWEEN BLOOD PRESSURE AT DISCHARGE AND THE LONG-TERM CLINICAL OUTCOME IN PATIENTS WHO UNDERWENT CARDIAC REHABILITATION

Objective: There is concern that excessive blood pressure (BP) lowering may result in worsening of prognosis in patients with cardiovascular diseases. We examined the relationship between BP levels at discharge and prognosis in patients who underwent cardiac rehabilitation. Design and Method: One hundred and fifty-four consecutive cases (133 patients; 69 males, 79 ± 12 years, mean ± SD) who discharged after cardiac rehabilitation were studied. The initial causes of admission were worsening of heart failure (HF, n = 101), acute myocardial infarction (n = 38), rehabilitation post cardiovascular surgery (n = 9), and acute aortic dissection (n = 4). The occurrence of composite events (rehospitalization for cardiovascular events or all-cause death) up to 2 years was investigated. The mean follow-up period was 440 days (2–731 days). Results: A total of 72 composite events occurred (rehospitalization, n = 58; all-cause death, n = 14). The event rate was lowest in the fourth systolic BP (SBP) quintile (Q4, SBP 115–125 mmHg). Hence, we recategorized the Q1-Q3, the Q4, and the Q5 into the low (L, n = 94), the middle (M, n = 28), and the high (H, n = 32) SBP group in the subsequent analyses. The event rates in the L, M, and H group were 54%, 25%, and 44%, respectively (p = 0.02). A multivariate Cox proportional hazards model, including significant factors in univariate analyses, demonstrated that age (hazard ratio (HR) /1year, 1.057; 95% CI, 1.002–1.095; p = 0.002) and blood pressure (HR of the middle BP group, 0.353; 95%CI, 0.156–0.795; p = 0.012) were independent predictors of the composite events. Conclusions: There was a J-shaped curve relationship between the systolic BP at discharge and the long-term prognosis in patients who underwent cardiac rehabilitation: the event rate was lowest in the group with systolic BP of 115–125 mmHg.

MPS 04-06 A SUPINE-SITTING FALL OF SYSTOLIC BLOOD PRESSURE WAS A PROGNOSTIC FACTOR IN PATIENTS WITH CARDIAC DISEASE AND LOW BLOOD PRESSURE

Objective: In our previous study, a J-shaped curve relationship was observed between sitting blood pressure (BP) and long term prognosis in patients with cardiac disease; the patients with sitting systolic BP (SBP) 115–125 mmHg had best prognosis. In the present analysis, we tried to examine prognostic factors in patients with SBP <115 mmHg. Design and Method: Eighty-nine consecutive cases (78 patients; age, 79 ± 12 y; male 47%) who discharged after cardiac rehabilitation and whose sitting SBP at discharge was <115 mmHg were studied. The causes of index hospitalizations were as follows; acute worsening of heart failure, n = 62: acute myocardial infarction, n = 20: rehabilitation after cardiovascular (CV) operation, n = 4: acute aortic dissection, n = 1. Two-year prognostic factors for composite events (admission due to CV disease and all-cause death) were investigated. The follow-up periods were 2–731 days (mean, 388 days). Results: Fifty composite events (admission due to CV diseases, 41: all-cause death, 9) occurred. Supine SBP and sitting SBP of the patient group with the events (E group) and without them (nonE group) were comparable. The decline of SBP from supine to sitting position (&Dgr;SBP) was greater in the E group than that in the nonE group (12 ± 15 mmHg, 5 ± 9 mmHg, respectively, p = 0.01). Receiver operating characteristics curve analysis revealed that 13.3 mmHg was the optimal cut-off point of &Dgr;SBP to predict the composite event (area under curve, 0.641). Age, eGFR, left ventricular mass index, and &Dgr;SBP ≥ 13.3 mmHg were the significant prognostic factors for the composite events in the Cox proportional hazards model including significant factors in univariate comparisons. Conclusions: The &Dgr;SBP was a significant prognostic factor in patients with cardiac diseases and low BP, suggesting that the &Dgr;SBP may be an indicator of excessive lowering of BP for these patients.