High-density lipoprotein cholesterol (HDL-C) has been identified as a powerful independent negative predictor of cardiovascular disease. The beneficial effect of HDL is largely attributable to its key role in reverse cholesterol transport, whereby excess cholesterol in the peripheral tissues is transported to the liver, reducing the atherosclerotic burden. However, mounting evidence indicates that HDL also has pleiotropic properties, such as anti-inflammatory, anti-oxidative, and vasodilatory properties, which may contribute in reducing the incidence of heart failure. Actually, previous data from clinical and experimental studies have suggested that HDL exerts cardioprotective effects irrespective of the presence/absence of coronary artery disease. This review summarizes the currently available evidence regarding beneficial effects of HDL on the heart beyond its anti-atherogenic property. Understanding the mechanisms of cardiac protection by HDL will provide new insight into the underlying mechanism and therapeutic strategy for heart failure.

The advent of new chemotherapeutic and immunotherapeutic treatments has markedly improved outcomes in patients with cancer. However, increasing numbers of elderly patients with cancer and prolonged periods of treatment have made the management of cardiovascular complications and treatment-induced cardiotoxicity an important concern, and onco-cardiology has received increasing attention. The number of patients with cardiotoxicity, particularly atherosclerotic lesions, and the usage of angiogenesis inhibitors have increased, making the involvement of onco-cardiologists essential for effective disease management. A paradigm shift in immunotherapy was caused by the development of immune checkpoint inhibitors. Because vascular endothelial growth factors (VEGF) in the cancer microenvironment and cancer immune function are interrelated angiogenesis inhibitors will most likely play an increasingly important role in combined immunotherapy. To ensure the optimal long-term diagnosis and long-term treatment of cancer and the effective management of treatment-related atherosclerotic diseases, the long-term continuous participation of onco-cardiologists is essential.

Aim: We aimed to investigate the association between reduced lung function and cerebral small vessel diseases via cranial magnetic resonance imaging (MRI) in the cross-sectional study of the general Japanese population.

Methods: We recruited participants aged ≥40 years from the general population of a single city in Japan. We clarified the comorbidities and treatments, smoking habits, second-hand smoke exposure, current alcohol consumption, education level, exercise habits, and occupation. The pulmonary function test was performed to assess the forced expiratory volume in 1 second (FEV₁) % predicted and forced vital capacity (FVC) % predicted values. Cranial MRI was performed to evaluate the white matter lesions (WMLs) and lacunar infarcts. We examined the association of the WMLs and lacunar infarcts with a 1-standard deviation (SD) lower in the FEV₁ % predicted and FVC % predicted, on the basis of the smoking status.

Results: A total of 473 men were examined. The association of WMLs and lacunar infarcts with the spirometry-based indices were significant only in never smokers. The association between lung function impairment and cerebral small vessel disease did not change after further adjusting for second-hand smoke exposure.

Conclusion: In a community-based sample of Japanese men, we found an association between reduced lung function and WMLs and lacunar infarcts in never smokers.

Aims: Coronary artery atherosclerosis in patients needing carotid revascularization has not been fully clarified. The aim of this study was to evaluate the stenotic severity and plaque characteristics of coronary arteries by coronary computed tomography angiography (CTA) in patients scheduled for carotid-artery stenting (CAS) or carotid endarterectomy (CEA).

Methods: We performed coronary CTA after carotid ultrasound (US) in 164 patients (81.7% male, aged 68.1± 12.2 years) from 2014 to 2016. Of all, 70 were scheduled for CAS or CEA (CAS/CEA group) and 94 were not (non-CAS/CEA group). Carotid US and coronary CTA were compared for the evaluation of stenotic severity and plaque characteristics of each vessel between CAS/CEA and non-CAS/CEA groups.

Results: Between the two groups, there were significant differences in the presence of significant stenosis (SS: ≥70% stenosis of coronary artery) (55.7% vs. 39.4%, P=0.038), triple-vessel disease (TVD)/left main trunk (LMT) (SS in each of three epicardial vessels and/or LMT) (24.3% vs. 7.5%, P= 0.0025), and high-risk plaque (HRP: positive remodeling and/or low attenuation) (55.7% vs. 24.5%, P＜0.0001). CAS/CEA was independently associated with TVD/LMT (OR=2.30, 95%CI: 1.14–8.59, P=0.026) and HRP (OR=3.17, 95%CI: 1.57–6.54, P=0.0012) in multivariable logistic regression analysis. Similarly, vulnerable plaque (78.6% vs. 2.1%, P＜0.0001) as well as severe stenosis of carotid artery (98.6% vs. 0%, P＜0.0001) was seen more often in CAS/CEA than in non-CAS/CEA group.

Conclusions: The prevalence of TVD/LMT and HRP determined by coronary CTA is higher in patients needing CAS/CEA than in those without. Management of systemic atherosclerosis is required in the perioperative period of CAS/CEA.

Aims: To investigate the association between circulating oxidized low-density lipoprotein (ox-LDL) levels and progression of subclinical atherosclerosis and to examine whether this link is independent of other low-density lipoprotein (LDL)-related parameters.

Methods: Totally, 804 subjects who were free of cardiovascular disease at baseline completed risk factor surveys and carotid ultrasound measurements in 2002 and 2012. Modified Poisson regression was performed to examine the association between baseline serum ox-LDL levels and the 10-year risk of progression of carotid atherosclerosis which was defined as the development of at least one new plaque in a previously plaque-free carotid segment at re-examination.

Results: The mean age of the subjects was 58.6±7.7 years at baseline and 43.3% were men. A total of 504 (62.7%) subjects had carotid plaque progression at re-examination. Subjects in the intermediate and highest tertiles of ox-LDL had a significantly higher adjusted risk of atherosclerosis progression than those in the lowest tertile [relative risk (95% confidence interval) 1.17 (1.01–1.34) for the intermediate tertile and 1.23 (1.07–1.42) for the highest tertile]. This association was independent of baseline levels of LDL-C, total LDL particle number, and small LDL particle number.

Conclusion: This study demonstrates that serum ox-LDL levels predict 10-year progression of subclinical atherosclerosis. Moreover, this effect is independent of the cholesterol content, the number, and the size of LDL particles.

Aim: Increased epicardial fat volume (EFV) is an independent risk factor for acute coronary syndrome (ACS). Although EFV increases with body mass index (BMI), some ACS patients have an increased EFV but normal BMI. We here investigated the clinical characteristics of nonobese ACS patients with an increased EFV.

Methods: A total of 197 Japanese patients hospitalized for ACS was evaluated for EFV, abdominal visceral fat area (VFA), and lipid and glucose profiles. Control subjects comprised 141 individuals who were suspected of having ACS but whose coronary computed tomography findings were normal.

Results: EFV was increased in ACS patients compared with control subjects (120±47 versus 95±45 mL, P＜0.01). ACS patients were divided into four groups based on average EFV (120 mL) and a BMI obesity cutoff of 25 kg/m². For the 30 nonobese ACS patients with an above-average EFV, EFV was positively correlated with VFA (r=0.23, P=0.031). These individuals were significantly older (74±10 years) and tended to have a higher homeostasis model assessment–insulin resistance value (5.5±3.8) compared with other ACS patients. Among nonobese study subjects, EFV was independently associated with ACS (odds ratio=2.01, P=0.021) and correlated with abdominal circumference (r=0.26, P=0.017).

Conclusion: Nonobese ACS patients with an increased EFV were elderly and tended to manifest insulin resistance. Measurement of EFV may prove informative for evaluation of ACS risk among elderly nonobese individuals with an increased abdominal girth.

Aim: It remains unclear whether measures used in carotid ultrasonography such as the intima–media thickness (IMT) and ultrasonic tissue characterization of the carotid using the gray-scale median (GSM) can add prognostic information beyond the conventional cardiovascular risk markers in patients with diabetes.

Methods: This study employed a combined analysis of data obtained in five longitudinal studies including a total of 3263 patients with diabetes but without apparent cardiovascular disease (CVD) at baseline. The associations between carotid ultrasonography measures and the first occurrence of CVD (488 cases), which were defined as cardiovascular death, coronary artery diseases, stroke, or peripheral artery disease, were analyzed.

Results: Common carotid artery (CCA)-mean-IMT, CCA-max-IMT, Max-IMT, plaque-GSM, and the presence of low-GSM echolucent plaques at baseline were prognostic factors for CVD even after adjustment for conventional risk factors. Time-dependent receiver-operating-characteristic (ROC) curve analysis indicated that the use of CCA-mean-IMT, CCA-max-IMT, and Max-IMT in addition to the conventional risk factors improved significantly the prediction of occurrence of CVD. Increments in the CCA-mean-IMT (hazard ratio [HR] 2.37 for every 0.1-mm/year increment [95% confidence interval [CI]: 1.63–3.47], p＜0.001), Max-IMT (HR 1.51 for every 0.1-mm/year increment [95% CI: 1.07–2.14], p=0.020), and Mean-GSM (HR 0.22 for every 10-U/year increment [95% CI: 0.06–0.76], p=0.016) during the observation period were also prognostic factors for CVD even after adjusting for the baseline value of the respective measure.

Conclusions: Addition of carotid ultrasonography measures to conventional risk factors significantly improved the stratification of patients by cardiovascular risk. Changes over time in carotid ultrasonography measures may be used as therapeutic outcome measures.

Aim: Progress in neuroimaging techniques allows us to investigate the microvasculature characteristics including lenticulostriate arteries (LSA), which are closely associated with lacunar infarction. Because ischemic stroke is a more critical health problem in East Asian than in other populations, in order to clarify pathological changes underlying cerebral small vessel disease (SVD), we projected an imaging analysis of LSA using high-resolution brain magnetic resonance imaging (MRI) in middle-aged Japanese subjects with type 2 diabetes.

Methods: Twenty-five subjects with type 2 diabetes and 25 non-diabetic control subjects underwent 7 Tesla (7 T) brain MRI. The prevalences of SVD and LSA structural changes were determined in each group.

Results: SVD prevalence did not differ significantly between the type 2 diabetes and control groups. The average numbers of stems, as well as numbers of branches, of LSA were significantly smaller in diabetic subjects than non-diabetic control subjects. The signal intensity of LSA was markedly decreased, indicating reduced blood flow in type 2 diabetes.

Conclusion: In spite of the prevalence of SVD being similar, structural changes and decreased signal intensity of LSA were highly detected in diabetic subjects compared with non-diabetic controls, suggesting that 7 T MRA enables us to determine LSA impairment prior to the development of SVD. Early detection of LSA impairment allows us earlier interventions aimed at the prevention of atherosclerotic events.

We report a case of Tangier disease with Leriche syndrome and bleeding tendency. In this male patient, nasal hemorrhage had been observed frequently throughout childhood. At 46 years old, he experienced effort angina, and coronary angiography demonstrated 75% stenosis in the right coronary artery. Orange-colored tonsils, mild hepatosplenomegaly and very low levels of serum high-density lipoprotein cholesterol (HDL-C) were observed, and the patient was diagnosed with Tangier disease. At 52 years old, effort angina recurred. Coronary angiography revealed 75% stenosis of the left main trunk, left anterior descending, and right coronary arteries. Stenosis of the brachiocephalic and right common iliac arteries was also recorded. Stents were implanted, and coronary artery bypass surgery was performed. At 53 years old, 15 months after surgery, the patient reported intermittent claudication, coldness of feet, and impotence. Aortic angiography showed progression of the stenosis at the bifurcation of the common iliac artery. The patient was diagnosed with Leriche syndrome, and aorta–left external iliac artery graft bypass surgery was performed. After surgery, oozing from subcutaneous tissue and leaking from the anastomotic region were observed. Additional analysis revealed two single-nucleotide polymorphisms (V825I and N935T) in the ATP-binding cassette transporter A1 (ABCA1) gene, and accumulation of small dense low-density lipoprotein together with low levels of HDL-C. In Tangier disease, HDL-C is markedly decreased because of ABCA1 deficiency. However, this is the first reported case to exhibit extensive atherosclerosis and bleeding tendency. This patient had atypical extensive and multiple atherosclerotic lesions, accompanied by Leriche syndrome and uncontrollable bleeding.