Hiroyuki Okuyama

Seasonal Blood Pressure Variation and Its Relationship to Environmental Temperature in Healthy Elderly Japanese Studied by Home Measurements

The purpose of the present study was to examine seasonal blood pressure variation and its relationship to environmental temperature in healthy elderly Japanese, as studied by home measurements. Fifteen healthy elderly Japanese (79.3 ± 5.9 yrs) measured their blood pressure at home each morning for more than 25 times per month for 3 years. Monthly mean outdoor temperatures were obtained from the Takamatsu meteorological Observatory. The highest levels of systolic and diastolic blood pressure measured at home were observed in February (129 ± 14 and 81 ± 13 mmHg). The lowest levels of systolic and diastolic blood pressure measured at home were observed in August (117 ± 11 and 73 ± 10 mmHg). Likewise, the lowest and highest means of outdoor temperature were observed in February (5.0°C) and August (29.2°C), respectively. Hence, both systolic and diastolic blood pressure demonstrated a close inverse correlation with the means of outdoor temperature (r = −0.973, p < 0.001 and r = −0.985, p < 0.001, respectively). A 1°C decrease in the mean outdoor temperature was associated with rises of 0.43 mmHg in systolic blood pressure (SBP) and 0.29 mmHg in diastolic blood pressure (DBP). Seasonal variations in home blood pressure and outdoor temperature showed complete correspondence in healthy elderly Japanese, with the blood pressures being inversely related to the ambient temperature. These seasonal home blood pressure variations should be kept in mind when controlling blood pressure in elderly patients.

Comparison of central blood pressure and cardio-ankle vascular index for association with cardiac function in treated hypertensive patients

Recent automated applanation tonometry can measure radial pulse wave-derived central blood pressure (CBP), which has shown a prognostic value independently of peripheral blood pressure. However, CBPs clinical significance has not been fully established. We examined the associations between CBP and cardiac structure and function by comparing them with those of arterial stiffness assessed by cardio-ankle vascular index (CAVI) in treated hypertensive patients. Enrolled in the study were 102 patients (71±7 years) with treated hypertension. The transmitral early-to-atrial velocity ratio (E/A), peak systolic (S′), early diastolic (E′) mitral annular velocities and the Tei index were measured as indexes of cardiac function derived from conventional and tissue Doppler echocardiography. Left ventricular mass index (LVMI) was measured as an index of LV hypertrophy. CBP and CAVI were measured just after echocardiographic examination. CBP, but not CAVI, correlated with LVMI (r=0.306, P<0.01). Although CBP correlated only with the Tei index (r=0.201, P<0.05), CAVI correlated with E/A (r=−0.387, P<0.001), S′ (r=−0.270, P<0.01), E′ (r=−0.362, P<0.01) and the Tei index (r=0.339, P<0.01). Stepwise regression analysis revealed that neither CBP nor CAVI was independently associated with E/A, S′ or E′. However, CAVI, but not CBP, was independently associated with the Tei index (β coefficient=0.311, P<0.001), reflecting both LV systolic and diastolic function. In conclusion, CBP may be suitable for detecting LV hypertrophy. In contrast, CAVI may be suitable for detecting LV dysfunction. This difference, suggesting the clinical value of each parameter, should be kept in mind when we use CBP and CAVI for assessing arteriosclerosis in treated hypertension.

Echocardiographic Assessment of the Cardio-Renal Connection: Is Left Ventricular Hypertrophy or Diastolic Function More Closely Correlated with Estimated Glomerular Filtration Rate in Patients with Cardiovascular Risk Factors?

Although left ventricular (LV) hypertrophy and diastolic function assessed by echocardiography and chronic kidney disease (CKD) have been established as predictors of cardiovascular events in hypertensive patients, the relationships between the echocardiographic parameters and renal function have not been fully examined. We examined which echocardiographic parameter correlates best with estimated glomerular filtration rate (eGFR) in patients with cardiovascular risk factors. Enrolled in the study were 309 patients (mean age 67 ± 13 y) with cardiovascular risk factors. Echocardiography was performed to measure left ventricular mass index (LVMI) as an index of LV hypertrophy. Transmitral early to atrial velocity (E/A) ratio and peak early diastolic mitral annular velocity (E′) were measured as indexes of LV diastolic function. E/E′ was calculated as a parameter of LV preload. eGFR was measured using the equation proposed by the Japanese Society of Nephrology. The correlations of LVMI (r = −0.333, p < 0.001) and hypertension (r = −0.326, p < 0.001) to eGFR were closer than those of E′ (r = 0.276, p < 0.001) and E/A (r = 0.224, p < 0.001) to eGFR. Stepwise regression analysis showed that hypertension (β coefficient = −0.211, p < 0.001) and LVMI (β coefficient = −0.206, p < 0.001) were independently associated with eGFR. The E/E′ increased with a decrease in eGFR, and E/E′ in CKD stage 5 (16.0 ± 6.8) was significantly higher than that in patients in whom eGFR ≥ 90 mL/min/1.73 m2 (10.5 ± 4.5) (p < 0.001). Left ventricular diastolic function may be influenced by the increase in LV preload due to progression of CKD stage. Therefore, LV hypertrophy may be superior to LV diastolic dysfunction in predicting low eGFR in patients with CKD using echocardiography.

Influences of Hypertension and Diabetes on Normal Age-Related Changes in Left Ventricular Function as Assessed by Tissue Doppler Echocardiography

Although the impact of hypertension (HT) and type 2 diabetes mellitus (DM) on left ventricular (LV) function has recently been studied using tissue Doppler echocardiography (TDE), there are few studies discriminating between the impact of the disease and that of normal aging on LV function. The purpose of the present study was to elucidate the LV function in patients with HT and DM in various age strata in order to assess the independent roles of HT and DM on normal age-related changes in cardiac function. The population of the study consisted of four groups: 20 control subjects (Control), 20 patients with hypertension alone (HTN), 20 patients with type 2 diabetes alone (DM), and 20 patients with both hypertension and diabetes (HTN+DM) in each of five age strata—the 40s, 50s, 60s, 70s, and 80s. The strain and strain rate, which reflected both LV systolic and diastolic function, were assessed by TDE. The strain and strain rate decreased with advancing age in healthy control subjects and in all the patient groups. The strain and strain rate in the HTN group and the DM group showed lower values than those in the healthy control subjects in each age stratum. Furthermore, the strain and strain rate in the HTN+DM group showed the lowest values among all four groups in each age stratum. These results indicate that LV function as assessed by TDE demonstrates age-related deterioration with normal aging. Although HT or DM affects normal age-related changes in LV function, the co-existence of HT and DM has a more harmful effect on the normal age-related changes than HT alone or DM alone.

Aortic root dilatation as a marker of subclinical left ventricular diastolic dysfunction in patients with cardiovascular risk factors.

Consensus is lacking about the clinical importance of aortic root dilatation in assessment of the risk of cardiovascular disease. In this study, correlations between aortic root diameter and echocardiographic features of left ventricular (LV) diastolic function were investigated in 333 patients with at least one cardiovascular risk factor (hypertension, diabetes or dyslipidaemia) and preserved LV systolic function. Aortic root diameter was measured by M-mode echocardiography, and LV diastolic function was evaluated by measuring the peak velocity of early (E) and late (A) diastolic transmitral blood flow and peak early diastolic mitral annular velocity (E′) by Doppler echocardiography. Linear regression analysis showed that, in men, age was no related to aortic root diameter but hypertension and LV hypertrophy were, whereas the converse was true in women. The parameters E, E/A ratio and E′, were related to aortic root diameter in both sexes. Stepwise multiple regression analysis confirmed that E in women and E′ in men were independently associated with aortic root diameter. It is concluded that aortic root dilatation might be a useful marker of subclinical LV diastolic dysfunction. Patients with preserved systolic function showing aortic root dilatation should, therefore, be given preventative therapy against LV diastolic heart failure.

Propensity Score Analysis of Regorafenib Versus Trifluridine/Tipiracil in Patients with Metastatic Colorectal Cancer Refractory to Standard Chemotherapy (REGOTAS): A Japanese Society for Cancer of the Colon and Rectum Multicenter Observational Study

This article compares the efficacy between regorafenib and trifluridine/tipiracil in patients with metastatic colorectal cancer refractory to standard chemotherapy, who had access to both drugs, to determine whether a further prospective comparative trial should be conducted.

C-Reactive Protein Level Is an Indicator of the Aggressiveness of Advanced Pancreatic Cancer.

Objectives This study investigated the ability of serum levels of C-reactive protein (CRP) to stratify the aggressiveness of advanced pancreatic cancer (PCa), including poor outcomes, systemic weakness, and extent of the disease in patients receiving first-line chemotherapy. Methods The prognostic CRP classification was constructed in the retrospective cohort, consisting of advanced PCa patients with first-line gemcitabine monotherapy (GEM). Stratification using the prognostic CRP classification was validated for relationships with the aggressiveness of advanced PCa in the prospective cohort, consisting of treatment-naive patients without obvious infections who received first-line GEM or GEM-based regimens. Results C-reactive protein low (<0.5 mg/dL), intermediate (≥0.5 and <2.0 mg/dL), and high (≥2.0 mg/dL) related good, moderate, and poor survival, respectively, and were independent predictors of survival in multivariate analyses among the 280 patients in the retrospective cohort and the 141 patients in the prospective cohort. Low Karnofsky Performance Status, hypoalbuminemia, anemia, and large tumor burden were more common in the high CRP group than in the low CRP group. The intermediate CRP group showed a larger burden of tumor than the low CRP group. Conclusions C-reactive protein stratified the outcomes, systemic weakness, and tumor burden. C-reactive protein is an indicator of the aggressiveness of advanced PCa.

Prognostic Factors in Patients with Hepatocellular Carcinoma Refractory or Intolerant to Sorafenib

Objective: The aim of this study was to identify the prognostic factors in patients with advanced hepatocellular carcinoma (HCC) who are refractory or intolerant to sorafenib and to exclude unsuitable candidates from subsequent therapy. Methods: The study cohort consisted of 111 patients who had discontinued sorafenib therapy. Uni- and multivariate analyses were conducted to identify the prognostic factors for survival after discontinuation of sorafenib therapy. Results: The median age of the patients was 70 years, and 96 of them (86%) were male. The Eastern Cooperative Oncology Group performance status was 0-1 in 94 patients (85%). Forty patients (36%) were classified as Child-Pugh class A and 57 (51%) as Child-Pugh class B. The median survival time after discontinuation of sorafenib therapy was 146 days. Hepatitis C viral antibody negativity, presence of ascites, absence of a history of previous treatment excluding sorafenib, elevated serum total bilirubin level, and elevated serum α-fetoprotein level were identified as the independent unfavorable prognostic factors by multivariate analysis. The median survival time of the patients with 4 or 5 unfavorable prognostic factors was 59 days. Conclusions: We should judge the indication of any subsequent therapy carefully in patients with 4 or 5 of the aforementioned factors.

Chemotherapy for advanced poorly differentiated pancreatic neuroendocrine carcinoma

Pancreatic neuroendocrine carcinoma (P‐NEC) resembles small cell lung carcinoma in its biologic and clinical features, such as rapid growth and relatively high sensitivity to platinum‐based chemotherapy. And, etoposide plus cisplatin (EP) or irinotecan plus cisplatin (IP), recommended by guidelines for the treatment of small cell lung carcinoma, has also been widely used for the treatment of unresectable NEC. Both regimens have been demonstrated to show favorable efficacy and have been acknowledged as de facto standard regimens for unresectable NEC, although it remains unclear which of the two regimens might yield more favorable outcomes. Therefore, a phase III trial of EP vs. IP has been planned for unresectable gastrointestinal, hepatobiliary or pancreatic NEC by the Japan Clinical Oncology Group. For patients with unresectable NEC who are refractory or intolerant to these regimens, no standard regimens have been established. Everolimus, an mTOR inhibitor, is likely to be effective in such patients, as there have been sporadic reports of the usefulness of everolimus in the treatment of P‐NEC. A multicenter phase II trial is underway to elucidate the efficacy and safety of everolimus in patients with P‐NEC who are refractory or intolerant to EP or IP.

Successful Everolimus Treatment in a Patient with Advanced Pancreatic Neuroendocrine Tumor Who Developed Everolimus-Induced Interstitial Lung Disease on Two Occasions: A Case Report

Chemotherapy-associated interstitial lung disease (ILD) is often fatal, and the chemotherapeutic regimen generally cannot be resumed. ILD associated with the mammalian target of rapamycin (mTOR) inhibitor everolimus has many features distinct from chemotherapy-associated ILD. We present the case of a 58-year-old woman with an advanced pancreatic neuroendocrine tumor with liver metastases, in whom everolimus treatment was maintained and resulted in a partial response despite two occurrences of everolimus-induced ILD during a 31-month treatment period until disease progression. Physicians treating with everolimus should monitor patients closely for ILD and should apply appropriate management strategies to optimize the possibility of maintaining everolimus therapy.