Screening method for severe sleep-disordered breathing in hypertensive patients without daytime sleepiness

SummaryThe high prevalence of sleep-disordered breathing (SDB) in hypertensive patients has been well studied. However, regular screening of SDB in these patients is not performed routinely as the diagnostic procedures are both time-consuming and labour-intensive. Overnight portable device screening is useful, but is sometimes not acceptable for asymptomatic SDB patients. We evaluated the usefulness of daytime 30-min recording with a portable recording device during pulse wave velocity (PWV) measurement sessions as a screening method for detection of asymptomatic SDB in hypertensive patients. Eighty-one hypertensive patients underwent 30-min daytime screening session using a Type III portable recording device during PWV measurement. Each screening session was followed by full overnight Level I polysomnography (PSG). The screening session included recordings of airflow (mouth–nose), chest movement, oximetry, and electrocardiography. The correlation coefficient between respiratory disturbance index (RDI) by screening session and apnea–hypopnea index (AHI) by PSG was 0.64. Using AHI ≥30 as diagnostic of severe SDB, 47 of 80 patients had the disorder based on PSG results. Using an RDI cut-off value of 22, the sensitivity and specificity for detection of severe SDB were 86.1% and 64.5%, respectively. Daytime 30-min recording with a portable device for apnea detection during PWV recording is useful for screening of asymptomatic severe SDB in hypertensive patients

Efficacy and safety of alirocumab in patients with hypercholesterolemia not adequately controlled with non-statin lipid-lowering therapy or the lowest strength of statin : ODYSSEY NIPPON study design and rationale

Background: Statins are generally well-tolerated and serious side effects are infrequent, but some patients experience adverse events and reduce their statin dose or discontinue treatment altogether. Alirocumab is a highly specific, fully human monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9), which can produce substantial and sustained reductions of low-density lipoprotein cholesterol (LDL-C). Methods: The randomized, double-blind, placebo-controlled, parallel-group, phase 3 ODYSSEY NIPPON study will explore alirocumab 150 mg every 4 weeks (Q4W) in 163 Japanese patients with hypercholesterolemia who are on the lowest-strength dose of atorvastatin (5 mg/day) or are receiving a non-statin lipid-lowering therapy (LLT) (fenofibrate, bezafibrate, ezetimibe, or diet therapy alone). Hypercholesterolemia is defined as LDL-C ≥ 100 mg/dL (2.6 mmol/L) in patients with heterozygous familial hypercholesterolemia or non-familial hypercholesterolemia with a history of documented coronary heart disease, or ≥120 mg/dL (3.1 mmol/L) in patients with non-familial hypercholesterolemia classified as primary prevention category III (i.e. high-risk patients). During the 12-week double-blind treatment period, patients will be randomized (1:1:1) to receive alirocumab subcutaneously (SC) 150 mg Q4W alternating with placebo for alirocumab Q4W, or alirocumab 150 mg SC every 2 weeks (Q2W), or SC placebo Q2W. The primary efficacy endpoint is the percentage change in calculated LDL-C from baseline to week 12. The long-term safety and tolerability of alirocumab will also be investigated. Discussion: The ODYSSEY NIPPON study will provide insights into the efficacy and safety of alirocumab 150 mg Q4W or 150 mg Q2W among Japanese patients with hypercholesterolemia who are on the lowest-strength dose of atorvastatin, or are receiving a non-statin LLT (including diet therapy alone)

Efficacy and safety of alirocumab 150 mg every 4 weeks in hypercholesterolemic patients on non-statin lipid-lowering therapy or lowest strength dose of statin : ODYSSEY NIPPON

Background: Alirocumab, a fully human monoclonal antibody to proprotein convertase subtilisin/kexin type 9, given every 2 weeks (Q2W), significantly reduced low-density lipoprotein cholesterol (LDL-C) levels in Japanese hypercholesterolemic patients on background statin. We evaluated alirocumab 150 mg every 4 weeks (Q4W) in patients on lowest-dose statin or non-statin lipid-lowering therapy (LLT). Methods: ODYSSEY NIPPON was a double-blind study conducted in Japanese patients with LDL-C≥100 mg/dL (heterozygous familial hypercholesterolemia or non-familial hypercholesterolemia with coronary heart disease) or ≥120 mg/dL (non-familial hypercholesterolemia, Japan Atherosclerosis Society category III) on atorvastatin 5 mg/day or non-statin LLT. Patients were randomized (1:1:1) to subcutaneous alirocumab 150 mg Q4W, alirocumab 150 mg Q2W, or placebo for the 12-week double-blind treatment period (DBTP), followed by a 52-week open-label treatment period (OLTP). At entry into the OLTP, patients received alirocumab 150 mg Q4W, with possible up-titration to 150 mg Q2W at Week 24. Results: Least-square mean percent change in LDL-C from baseline at Week 12 (primary efficacy endpoint) was -43.8% for alirocumab Q4W, -70.1% for Q2W, and -4.3% for placebo. During the OLTP, mean LDL-C change from baseline was -45.1% at Week 20, with a further reduction at Week 36, with achieved levels maintained to Week 64. Percent of patients with≥1 adverse event (DBTP) was 51.9% with alirocumab Q4W, 47.2% with Q2W, and 46.4% with placebo. Most common adverse events were infections and infestations (25.9%, 22.6%, 17.9%, respectively), gastrointestinal disorders (13.0%, 9.4%, 12.5%), nervous system disorders (5.6%, 7.5%, 10.7%), and general disorders and administration-site conditions (3.7%, 11.3%, 5.4%). Conclusions: Hypercholesterolemic Japanese patients who tolerate only lowest-strength dose statin or non-statin LLT can achieve robust LDL-C reduction with alirocumab 150 mg Q4W, in addition to their current LLT. Alirocumab 150 mg Q4W dosing was efficacious and generally well tolerated without new safety concerns

Prevalence of the metabolic syndrome in elderly and middle-aged Japanese

AbstractBackground/PurposeDiagnosis and management of the metabolic syndrome (MetS) are beneficial for successful aging. In spite of several criteria for MetS, there is little information on cardiometabolic risk clustering in elderly Japanese. The purpose of this study was, therefore, to determine the relationship between age-associated changes in obesity and metabolic components in the Japanese.MethodsWe analyzed data from the nationwide survey conducted in 2000. Using Adult Treatment Panel III (ATP III) and Japanese diagnostic criteria for MetS, we analyzed 2366 people aged from 40 to 79 years (men, 1425 and women, 941) from the total participants.ResultsThe prevalence of MetS was almost three fold higher by modified ATP III, International Diabetes Federation, and Japanese criteria, in elderly women than in middle-aged women, whereas no difference was found between middle-aged and elderly men by the three criteria. A marked increase in the prevalence of MetS was found by modified ATP III and International Diabetes Federation criteria compared with that by the Japanese criteria in women. Among the risk factors, the prevalence of central obesity and dyslipidemia increased only in women and that of high fasting glucose and high blood pressure increased in both genders with aging. Among the MetS subjects who fulfilled the modified ATP III criteria, more clustering of risk was observed in elderly than in middle-aged subjects, especially in women. Blood pressure increased and triglyceride decreased in both genders, and non-high-density-lipoprotein cholesterol decreased in elderly men. The prevalence of dyslipidemia decreased in elderly men.ConclusionAging is an important factor that affects the metabolic abnormality, and aging of the population would lead to increase in the prevalence of MetS. Therefore, the development of better approaches to the prevention and management of MetS is necessary for successful aging in our society

Effects of daily aspirin on cancer incidence and mortality in the elderly Japanese

BackgroundLong‐term follow‐up of studies to investigate preventive effects of aspirin on arterial thrombosis indicate that aspirin reduces the incidence and mortality of some cancers in Western populations.ObjectivesTo explore the effects of aspirin on cancer incidence and mortality in the elderly Japanese.Patients/MethodsPatients aged 60 to 85 years, presenting with hypertension, dyslipidemia, or diabetes mellitus (n = 14 601, 7297 in the aspirin group and 7304 in the no‐aspirin group) participated the Japanese Primary Prevention Project (JPPP), a multicenter, open‐label, randomized, parallel‐group trial. A subanalysis of JPPP was performed to analyze the incidence of newly diagnosed cancer and death related to cancer.ResultsThe cumulative incidence of newly diagnosed cancer was 5.60% (4.65‐6.64%) in the aspirin group and 4.14% (3.67‐4.66%) in the no‐aspirin group. The hazard ratio for newly diagnosed cancer was 1.24 (1.06‐1.46), and the cancer incidence was significantly higher in the aspirin group. The cumulative cancer mortality was 1.96% (1.65‐2.31%) in the aspirin group and 1.87% (1.56‐2.22%) in the no‐aspirin group, with no statistically significant difference. The Fine and Gray model suggested that the difference in the incidence of newly diagnosed cancer between the two groups decreased year by year.ConclusionsLow‐dose aspirin use did not reduce the cancer incidence or cancer mortality during a 5‐year‐average study period in the elderly Japanese. The cancer incidence in the aspirin group might decrease, however, to less than that in the no‐aspirin group after the study period. Aspirin use might have led to earlier cancer diagnosis in our study

Sodium intake in men and potassium intake in women determine the prevalence of metabolic syndrome in Japanese hypertensive patients: OMEGA Study

Dietary intake affects hypertension and metabolic syndrome (MS) and their management. In Japanese hypertensive patients, little evidence exists regarding the relation between diet and MS. A self-administered lifestyle questionnaire was completed by each patient at the baseline. Three dietary scores were calculated for each patient: sodium intake, potassium intake and soybean/fish intake. The relationships between dietary scores and systolic blood pressure (SBP) and diastolic blood pressure (DBP) were analyzed by multiple regression analysis. The relation between dietary intake of sodium, potassium and soybean/fish, and the presence of MS was evaluated by the Mantel–Haenszel test. A total of 9585 hypertensive patients (mean age, 64.9 years; women, 51.4%) were included in this sub-analysis. High sodium intake was significantly related to increased SBP (P=0.0003) and DBP (P=0.0130). Low potassium intake was significantly related to increased SBP (P=0.0057) and DBP (P=0.0005). Low soybean/fish intake was significantly related to increased SBP (P=0.0133). A significantly higher prevalence of MS was found in men in the highest quartile of sodium intake compared with the lower quartiles (P=0.0026) and in women in the lowest quartile of potassium intake compared with the higher quartiles (P=0.0038). A clear relation between dietary habits and blood pressure was found in Japanese hypertensive patients using a patient-administered questionnaire. Sodium and potassium intake affect MS prevalence. Dietary changes are warranted within hypertension treatment strategies

Lipoprotein‐Associated Phospholipase A2 Activity Is a Marker of Risk But Not a Useful Target for Treatment in Patients With Stable Coronary Heart Disease

Background: We evaluated lipoprotein‐associated phospholipase A2 (Lp‐PLA2) activity in patients with stable coronary heart disease before and during treatment with darapladib, a selective Lp‐PLA2 inhibitor, in relation to outcomes and the effects of darapladib in the STABILITY trial. Methods and Results: Plasma Lp‐PLA2 activity was determined at baseline (n=14 500); at 1 month (n=13 709); serially (n=100) at 3, 6, and 18 months; and at the end of treatment. Adjusted Cox regression models evaluated associations between Lp‐PLA2 activity levels and outcomes. At baseline, the median Lp‐PLA2 level was 172.4 μmol/min per liter (interquartile range 143.1–204.2 μmol/min per liter). Comparing the highest and lowest Lp‐PLA2 quartile groups, the hazard ratios were 1.50 (95% CI 1.23–1.82) for the primary composite end point (cardiovascular death, myocardial infarction, or stroke), 1.95 (95% CI 1.29–2.93) for hospitalization for heart failure, 1.42 (1.07–1.89) for cardiovascular death, and 1.37 (1.03–1.81) for myocardial infarction after adjustment for baseline characteristics, standard laboratory variables, and other prognostic biomarkers. Treatment with darapladib led to a ≈65% persistent reduction in median Lp‐PLA2 activity. There were no associations between on‐treatment Lp‐PLA2 activity or changes of Lp‐PLA2 activity and outcomes, and there were no significant interactions between baseline and on‐treatment Lp‐PLA2 activity or changes in Lp‐PLA2 activity levels and the effects of darapladib on outcomes. Conclusions: Although high Lp‐PLA2 activity was associated with increased risk of cardiovascular events, pharmacological lowering of Lp‐PLA2 activity by ≈65% did not significantly reduce cardiovascular events in patients with stable coronary heart disease, regardless of the baseline level or the magnitude of change of Lp‐PLA2 activity