Patients with Stage A heart failure (HF) show no HF symptoms but have related comorbid diseases with a high risk of progressing to HF. Screening for comorbid diseases warrants closer attention because of the growing interest in addressing Stage A HF as the best means of preventing eventual progression to overt HF such as Stages C and D. The identification of individuals of Stage A HF is potentially useful for the implementation of HF-prevention strategies; however, not all Stage A HF patients develop left ventricular (LV) structural heart disease or symptomatic HF, which lead to advanced HF stages. Therefore, Stage A HF requires management with the long-term goal of avoiding HF development; likewise, Stage B HF patients are ideal targets for HF prevention. Although the early detection of subclinical LV dysfunction is, thus, essential for delaying the progression to HF, the assessment of subclinical LV dysfunction can be challenging. Global longitudinal strain (GLS) as assessed by speckle-tracking echocardiography has recently been reported to be a sensitive marker of early subtle LV myocardial abnormalities, helpful for the prediction of the outcomes for various cardiac diseases, and superior to conventional echocardiographic indices. GLS reflects LV longitudinal myocardial systolic function, and can be assessed usually by means of two-dimensional speckle-tracking. This article reviews the importance of the assessment of subclinical LV dysfunction in Stage A HF patients by means of GLS, and its current potential to prevent progression to later stage HF.
Aim: Although renal dysfunction has been identified as a novel risk factor affecting stroke prognosis, few have analyzed the association within large-scale population-based setting, using wide-range estimated glomerular filtration rate (eGFR) category. We aimed to determine the association of admission eGFR with acute stroke outcomes using data from a registry established in Shiga Prefecture, Japan.
Methods: Following exclusion of patients younger than 18 years, with missing serum creatinine data, and with onset more than 7 days prior to admission, 2,813 acute stroke patients registered in the Shiga Stroke Registry year 2011 were included in the final analysis. The Japanese Society of Nephrology equation was used to estimate GFR. Multivariable logistic regression was performed to analyze the association of eGFR with all-cause in-hospital death (modified Rankin Scale [mRS] 6), and at-discharge death/disability (mRS 2–6). Separate analyses were conducted within stroke subtypes.
Results: Compared to eGFR 60–89 mL/min/1.73 m2, adjusted odds ratios (ORs) and 95% confidence interval [95% CI] for in-hospital death (in the order of eGFR ＜45, 45–59, and ≥90 mL/min/1.73 m2) were 1.54 [1.04–2.27], 1.07 [0.72–1.58], and 1.04 [0.67–1.59]. Likewise, adjusted ORs [95% CI] for at-discharge death/disability were 1.54 [1.02–2.32], 0.97 [0.73–1.31], and 1.48 [1.06–2.05]. Similar pattern was further evident in the eGFR ＜45 mL/min/1.73 m2 group for both outcomes within acute ischemic stroke patients.
Conclusions: Our study has ascertained that in acute stroke, particularly ischemic stroke, low eGFR was significantly associated with in-hospital death and at-discharge death/disability. Additionally, high eGFR was found to be associated with at-discharge death/disability.
Aim: To evaluate the epidemiology and real-world treatment patterns associated with lipid-modifying therapies (LMTs) among groups of Japanese patients with familial hypercholesterolemia (FH).
Methods: A retrospective observational study was conducted using an electronic hospital-based administrative claims database and electronic medical records. Patients with existing diagnosis of FH (FH-D) and patients with suspected FH (FH-S) defined by low-density lipoprotein cholesterol (LDL-C) ≥190 mg/dL were included, and medical records of hospitals across Japan were analyzed to assess the diagnostic status, management of LDL-C levels, and treatment patterns.
Results: Among the 3,495 patients who met the inclusion criteria, 193 patients were FH-D and 3,339 patients were FH-S. Among them, 83.5% had not achieved the LDL-C of ＜100 mg/dL recommended for patients with FH at the index date. Mean LDL-C levels for all patients and for FH-D and FH-S patients were 145.8 mg/dL, 119.2 mg/dL, and 147.6 mg/dL, respectively. 44.5% of the patients were not currently treated with LMTs. High-intensity statins were used only in 19.2% and 2.3% of the FH-D and FH-S patients, respectively. Furthermore, among the FH-D and FH-S statin-treated patients, 61 (69.3%) and 1,059 (89.7%) remained on monotherapy even when their LDL-C was ≥100 mg/dL.
Conclusions: Treatment and management of LDL-C in Japanese FH patients remain suboptimal. The results suggest that FH is underdiagnosed in real-world, routine clinical practice in Japan. There is an urgent need to improve the diagnostic rate of FH and to provide the appropriate therapy to achieve the recommended LDL-C levels of ＜100 mg/dL or a more than 50% reduction for patients with FH in Japan.
Aim: We focused on the ratios of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) to arachidonic acid (AA) and explored the significance of these ratios relative to clinical characteristics by age in ischemic stroke patients.
Methods: We enrolled patients with acute ischemic stroke who underwent radiological investigations and laboratory examinations, including measurement of serum EPA, DHA, and AA levels, and controls. Patients were classified according to age (＜65, 65–74, and ≥ 75 years) and the tertile of EPA/AA and DHA/AA ratios, and clinical aspects were compared with these factors.
Results: We analyzed 373 patients (age 70.2±13.4 years; 245 males) and 105 controls. Among stroke patients, patients aged ＜65 years had the lowest EPA/AA (0.35±0.23, p=0.006) and DHA/AA (0.73±0.27, p＜0.001) ratios. Compared with controls, patients aged ＜65 years showed lower EPA/AA (vs. 0.49±0.25, p＜0.001) and DHA/AA (vs. 0.82±0.26, p=0.009) ratios. From logistic regression analysis, the EPA/AA (odds ratio 0.18, 95% confidence interval 0.04–0.81, p=0.026) and DHA/AA (odds ratio 0.09, 95% confidence interval 0.02–0.33, p＜0.001) ratios were inversely related to patients aged ＜65 years. According to age-stratified analyses, we found an association of aortic arch calcification with a lower EPA/AA ratio for patients aged ≥ 75 years and an association of multiple infarctions and cerebral white matter lesions with a lower EPA/AA ratio for patients aged 65–74 years (p＜0.05).
Conclusions: The ratios of EPA/AA and DHA/AA could be specific markers for younger stroke patients. The EPA/AA ratio may be related to aortic arch calcification for elderly stroke patients and to multiple infarctions and cerebral white matter disease for middle-aged stroke patients.
Aim: To investigate associations between socioeconomic status (SES) and the prevalence and treatment status of hypercholesterolemia in a general Japanese population.
Methods: In 2010, we established a cohort study of 2417 adults (age 20–91 yr) from 300 randomly selected areas across Japan who participated in the National Health and Nutrition Survey of Japan. We cross-sectionally examined an association between SES and (1) prevalence of hypercholesterolemia in 2417 participants (999 men and 1418 women) and (2) not receiving medication for hypercholesterolemia in 654 participants (215 men and 439 women). SES included employment status, marital status, length of education, and household expenditures. Hypercholesterolemia was defined as a total serum cholesterol level of ≥6.21 mmol/L (240 mg/dL) or the use of lipid-lowering medications.
Results: The overall prevalence of hypercholesterolemia was 21.5% in men and 31.0% in women. In men, the lowest quintile of household expenditures was associated with a higher prevalence of hypercholesterolemia (28.3%) compared with the upper 4 quintiles (19.9%) (multivariable-adjusted odds ratio 1.66; 95% confidence interval [CI] 1.16–2.38). Among participants with hypercholesterolemia, 55.4% of men and 55.1% of women were not receiving medication. Unmarried men were more likely to be untreated (75.0%) than married men (50.9%) (multivariable-adjusted odds ratio 2.53;95%CI 1.05–6.08). SES had no significant effects in women.
Conclusion: In a general population of Japanese men, low household expenditures were associated with a higher prevalence of hypercholesterolemia, and unmarried men with hypercholesterolemia were less likely to receive medication.
Aim: To investigate the associations of conventional lipid parameters with arterial stiffness assessed by cardio–ankle vascular index (CAVI).
Methods: A retrospective cross-sectional study was conducted in 23,257 healthy Japanese subjects (12,729 men and 10,528 women, aged 47.1±12.5 years, body mass index (BMI) 22.9±3.4 kg/m2) who underwent health screening between 2004 and 2006 in Japan.
Results: Male subjects had significantly higher BMI, CAVI and triglycerides (TG), and lower high-density lipoprotein cholesterol (HDL-C) compared to female subjects. After adjusting for confounders, including gender, age, systolic blood pressure and BMI identified by multiple regression analysis, adjusted CAVI was lower in normolipidemic than in dyslipidemic subjects. Among dyslipidemic subjects, those with hypertriglyceridemia had higher adjusted CAVI. A trend test detected linear relations between adjusted CAVI and all the conventional lipid parameters throughout the entire range of serum levels. After adjusting for confounders, logistic regression models showed that all lipid parameters contributed independently to high CAVI (≥90th percentile). Receiver–operating–characteristic analysis determined reliable cut-off values of 93 mg/dl for TG (area under the curve, AUC= 0.735), 114 mg/dl for low-density lipoprotein cholesterol (AUC=0.614) and 63 mg/dl for HDL-C (AUC=0.728) in predicting high CAVI. These cut-off values were confirmed to independently predict high CAVI in a bivariate logistic regression model.
Conclusion: The present study demonstrated independent contribution of conventional lipid parameters to CAVI, indicating a possible association of lipid parameters with early vascular damage.
Aim: The aims of this study were: 1) to determine whether the accumulation of aortic root calcification (ARC) assessed using coronary computed tomography angiography (CCTA) can predict future cardiovascular events, and 2) to estimate the onset and progression of ARC in patients with familial hypercholesterolemia (FH).
Methods: One hundred thirteen consecutive Japanese patients with heterozygous FH (male=54, mean age=52.1±15.6 years, mean LDL-C=299.0±94.6 mg/dL), without known coronary artery disease, who underwent 64-detector row CCTA were retrospectively evaluated. ARC was defined as the presence of calcium at the aortic root. The extent of ARC was expressed in Agatston units as the ARC-score. Major adverse cardiac events (MACE) were defined as either cardiac death, ST elevated myocardial infarction (STEMI), non-ST elevated myocardial infarction (NSTEMI), unstable angina pectoris (UAP), planned percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), or stroke. The periods to MACE were estimated using multivariate logistic regression analysis.
Results: During the follow-up period (median 1635 days), 19 instances of MACE occurred. Multivariate logistic regression analysis revealed that ARC was a significant independent predictor of MACE (OR=1.48; 95% CI 1.11–1.87, p＜0.001, respectively). The regression equations were Y=0.09X– 1.59 (R2=0.34, p＜0.001) in males and Y=0.08X–1.60 (R2=0.13, p＜0. 05) in females.
Conclusions: ARC was significantly associated with future MACE in Japanese patients with heterozygous FH. ARC may start to develop, on average, at 17.4 and 19.7 years of age in males and females, respectively, with heterozygous FH.
Aim: The Friedewald equation is the standard method for estimating low-density lipoprotein cholesterol (LDL-C) levels [LDL-C(F)] and fixes the ratio of triglyceride (TG) to very LDL-C at 5. However, this has been reported to underestimate LDL-C, particularly in patients with LDL-C ＜70 mg/dL. A novel method for LDL-C estimation [LDL-C(M)] using an adjustable factor instead of a fixed value of 5 has recently been proposed. The purpose of this study was to validate LDL-C(M) in Japanese patients with cardiovascular disease (CVD) treated with statins.
Methods: In 385 consecutive CVD patients treated with statins, LDL-C(M) and LDL-C(F) levels were compared with directly measured LDL-C [LDL-C(D)].
Results: Mean LDL-C(D), LDL-C(F), and LDL-C(M) were 81.7±25.5, 76.4±24.6, and 79.9±24.5 mg/dL, respectively. In all patients, both LDL-C(F) and LDL-C(M) were significantly correlated with LDL-C(D) [LDL-C(F) vs. LDL-C(D): R=0.974, p＜0.001; LDL-C(M) vs. LDL-C(D): R=0.987, p＜0.001]. In patients with LDL-C(D) ＜70 mg/dL, LDL-C(M) showed a better correlation with LDLC(D) compared with LDL-C(F) [LDL-C(M) vs. LDL-C(D): R=0.935, p＜0.001; LDL-C(F) vs. LDLC(D): R=0.868, p＜0.001]. In contrast, the correlation of LDL-C(D) with LDL-C(M) or LDL-C(F) was similar in patients with LDL-C(D) ≥70 mg/dL.
Conclusions: In Japanese patients with CVD treated with statins, LDL-C level estimated by this novel method might be more accurate than those estimated using the Friedewald equation for LDL-C levels ＜70 mg/dL.