LDL cholesterol is by far the best established “causal” cardiovascular risk. It is distributed normally, and the mean value ranges around 100~120 mg/dl. In terms of preventive cardiology, we now know very well that the lower the LDL cholesterol, the better. Clinical usefulness of aggressive LDL-lowering therapies using statin, ezetimibe, and proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors have been shown in primary and in secondary prevention settings. Additionally, the idea, based on recent randomized controlled trials (RCT), that the lower LDL cholesterol the better appears to be true for LDL as low as ~ 30 mg/dl. According to those data, recent guidelines in Europe and in Japan suggest the lowering of LDL cholesterol level ＜70 mg/dl for high-risk patients. However, the attainment rates of such “strict” goals seem to be quite low, probably because most cardiologists still have a sense of anxiety of “low” LDL cholesterol level. But “low” indicates no more than “lower” than the “average” range, which is not always implying the optimal range. Additionally, Mendelian randomization studies focusing on individuals exhibiting “low” LDL cholesterol suggest that “normal” LDL cholesterol levels might be too much for us. Moreover, LDL cholesterol levels of other primates are substantially lower than those in humans. In this review article, based on a series of evidence from clinical trials, human genetics, and biology, we provide the idea that we need to rethink what is the optimal range of LDL cholesterol level, instead of “normal” or “average” range.

Aim: Patients with obstructive sleep apnea (OSA) are likely to show increased arterial stiffness and progressive systemic atherosclerosis. Chest radiography reveals atherosclerotic changes in the aorta via measurement of aortic knob width. However, to our knowledge, aortic knob width in patients with OSA has never been evaluated.

Methods: We measured the aortic knob width in chest radiographs of 549 patients (age: 52.5±13.2 years; 69 women) who underwent overnight polysomnography. Moreover, we evaluated the association between aortic knob width and other clinical characteristics, including cardio–ankle vascular index (CAVI) and apnea–hypopnea index (AHI). Multivariate linear regression analysis was conducted to identify factors associated with aortic knob width.

Results: A significant direct correlation between aortic knob width and CAVI and between aortic knob width and AHI was observed. In multivariate linear regression analysis, either CAVI or AHI was independently associated with aortic knob width (p=0.004 and p＜0.001, respectively) in addition to age, male gender, body mass index, and systolic blood pressure.

Conclusion: A significant independent correlation between aortic knob width and OSA severity was observed. Our findings suggest that an increase in the aortic knob width suggests atherosclerotic changes in the aorta and may be associated with OSA and increased arterial stiffness.

Aim: An inverse association between diabetes mellitus (DM) and aortic dilatation has recently been reported. However, little is known about the association between DM and the progression of aortic dilatation/calcification as atherosclerosis progresses.

Methods: We identified 216 patients who had undergone percutaneous coronary intervention (PCI) and abdominal computed tomography (CT) during the PCI and follow-up phases. The patients were classified into two groups: those with DM (DM+ group; n=107) and those without DM (DM− group; n=109). The infrarenal aortic diameter and aortic calcification index (ACI) were measured, and annual changes were calculated using measurement results obtained during the PCI and follow-up phases.

Results: Infrarenal aortic diameters were significantly shorter in the DM+ group than in the DM- group during the PCI phase, and no significant ACI differences were observed between the DM+ and DM− groups. The median duration between the PCI and follow-up phase CT was 3.0 years. The growth rate of the infrarenal aortic dilatation from the PCI phase in the DM+ group was similar to that in the DM− group. Annual ACI changes were significantly larger in the DM+ group than in the DM− group. Multivariate logistic regression analysis indicated that the prevalence of DM was an independent predictor of rapid aortic calcification progression (odds ratio: 2.51; 95% confidence interval: 1.23-5.14; p=0.01).

Conclusion: Our findings suggest that DM negatively affects aortic dilatation during an earlier phase of atherosclerosis progression and positively affects the progression of aortic calcification in a later phase.

Aim: To investigate the impact of institutional volume on clinical outcomes after aortoiliac (AI) stenting in patients with symptomatic peripheral artery disease (PAD).

Methods: We analyzed the clinical database from the Observational prospective Multicenter registry study on the Outcomes of peripheral arTErial disease patieNts treated by AngioplaSty tHerapy in the aortoIliac artery (OMOTENASHI) registry. The volume of each institution was evaluated as the number of endovascular therapy (EVT) procedures performed in 2 years (2014–2015). High-volume centers were defined as being in the highest tertile of the procedural volume (≥ 611 EVT procedures in 2 years). Clinical outcomes, treatment strategies, and endovascular procedures were compared between high- and low-volume centers using a propensity score matching.

Results: The propensity score matching extracted 236 pairs of patients (as many patients treated at high-volume centers and 519 patients treated at low-volume centers), with no remarkable intergroup differences in the baseline characteristics. Patients treated at high-volume hospitals had a significantly lower 12-month restenosis rate than that of patients treated at low-volume hospitals (6.5% vs. 15.8%, P=0.032), although comparable outcomes between the two groups included the technical success rate (99.6% vs. 99.8%, P=0.58) and the rate of 30-day major adverse events (0.4% vs. 0.8%, P=0.59).

Conclusion: Institutional volume was associated with the 12-month restenosis rate after AI stenting for PAD, although comparable perioperative outcomes were also observed between high-volume and low-volume hospitals.

Aim: Posterior circulation stroke (PCS) has different clinical features and prognosis compared with anterior circulation stroke (ACS), and whether the effect of statin therapy on stroke prevention differs according to infarction location remains unclear. This post hoc analysis of the J-STARS study aimed to compare the usefulness of statin at different infarction locations (i.e., ACS and PCS).

Methods: In the J-STARS study, 1578 patients were randomly assigned to the pravastatin or control group. The subjects were divided into two subgroups (ACS and PCS groups) based on the arteries responsible for the infarction. Cox proportional hazards models were used to investigate whether the all stroke recurrence rate was different between the ACS and PCS groups.

Results: The PCS group (n=499) had a significantly higher prevalence of diabetes than the ACS group (n=1022) (30.7% vs. 19.8%, P＜0.001). During the follow-up (4.9±1.4 years), the incidence of all stroke was significantly lower in the pravastatin group than in the control group among patients with PCS (adjusted hazard ratio [HR] 0.46, 95% confidence interval [CI] 0.25–0.83, P=0.009); however, the stroke recurrence rates were not significantly different between both groups among patients with ACS (adjusted HR 1.32, 95% CI 0.93–1.88,P=0.123). A significant interaction between the ACS and PCS groups in terms of pravastatin effects was noted (P=0.003 for interaction).

Conclusions: Pravastatin significantly reduced the recurrence rate of all stroke among patients with PCS. Thus, the effect of statin on the recurrence of stroke may differ according to infarction location.

Aims: Metabolic syndrome (MetS) has become a worldwide epidemic; however, few studies have described its status in Chinese children. This study aimed to estimate MetS status and its associations with geography, economic development, birth weight, and parental education of Chinese children and adolescents.

Methods: Data were derived from 15,045 participants aged 7–18 years across seven Chinese provinces. Physical measurement and blood tests were conducted to assess the five classical MetS components described by the International Diabetes Federation, including abdominal obesity (the essential component), high blood pressure, low high-density cholesterol (HDL-C), high triglyceride, and elevated fasting glucose (FG). Logistic regression was adopted to explore possible associations between MetS and other factors.

Results: Overall, MetS prevalence was 2.3%, higher in males (2.8% vs. 1.7% in females), northern regions (3.1%), more developed regions (2.9%), and older participants (aged 16–18 years) (P＜0.05 for all). Among the five MetS components, abdominal obesity and low HDL-C level were most prevalent (21.8% and 14.4%), and 35.9% of the participants had at least one component. In logistic regression, MetS itself did not correlate with birth weight or parental education. High birth weight was positively correlated with abdominal obesity (odds ratio, 1.48) butnegatively associated with elevated FG (odds ratio, 0.49).

Concusions: MetS itself was not common in Chinese children and adolescents, whereas its certain components were far more prevalent. Children from North China, more-developed areas, and at an older age were more likely to develop MetS. Strategies designed to prevent pediatric MetS in China should focus on prevalent components as well as its geographic and economic development predilections.

Aim: Exosome-derived microRNAs (miRNAs) are potential diagnostic biomarkers. However, little is known about their effectiveness as diagnostic biomarkers of intracranial aneurysms (IAs). This study aimed to explore miRNA levels in plasma exosomes of patients with IA to identify potential biomarkers that predict the development and progress of IA.

Methods: A total of 69 patients with IA and 30 healthy controls (HC) were recruited, among whom 30 had unruptured IA (UA), and 39 had ruptured IA (RA). The miRNA expression profiles of plasma exosomes in 12 IA patients (4 UA and 8 RA) and 4 HC were determined using next-generation sequencing. In addition, significantly differentially expressed miRNAs were further analyzed by Quantitative Real-Time PCR (qRT-PCR) in a validation cohort of 99 subjects.

Results: From the sequencing analysis, 181 miRNAs were identified to be differently (p＜0.05) expressed. Of these, 9 miRNAs were up-regulated, and 20 were down-regulated in patients with UA compared with HC. Also, 21 were up-regulated, and 10 were down-regulated in patients with RA compared with HC. In addition, compared with UA, 92 miRNAs were up-regulated in RA, whereas 29 were down-regulated. Furthermore, qRT-PCR analysis confirmed that miR-145-5p and miR-29a-3p were up-regulated in IA samples. To distinguish IA patients from controls, the area under the receiver operating characteristic curve was 0.791 for miR-29a-3p, while that of miRNA-145-5p was 0.773 in terms of discriminating whether the aneurysm was ruptured.

Conclusions: Circulating exosomal miRNAs can serve as biomarkers of the development and progression of IA.

Aims: Arterial stiffness is known to be an important surrogate marker for atherosclerosis and predictor of peripheral vascular and cardiovascular (CV) disease. Whether high cardio-ankle vascular index (CAVI) is associated with the development of rapid glomerular filtration rate (GFR) decline remains uncertain. The study aimed to determine the relationship between CAVI and renal function progression among patients with high CV risk.

Methods: This study employed a prospective cohort design with 1-year follow-up among patients with high CV risk. Arterial stiffness was measured using CAVI method. GFR was estimated using the chronic kidney disease (CKD) epidemiology collaboration equation, and rapid decline in GFR was defined with decrease in GFR ≥ 5 mL/min/1.73 m² yearly.

Results: Of 352 patients with mean age 67.8±10.1 years, 224 patients (63.6%) were suspected to have arteriosclerosis (CAVI ≥ 9), and 208 patients (59.1%) had CKD (GFR ＜60 mL/min/1.73 m²). Annual decline of GFR was −0.75 [interquartile range (IQR), −1.16 to 6.08] mL/min/1.73 m²/year, and 30.1% of patients experienced a rapid decline in GFR. Compared with normal CAVI (CAVI ＜8), high CAVI (CAVI ≥ 9) and borderline CAVI (CAVI 8-8.9) in all subjects and subgroup of baseline GFR ＞60 mL/min/1.73 m² were associated with rapid GFR decline. Multivariable analysis showed that high CAVI and borderline CAVI were associated with 2.47-fold (95% CI, 0.89-6.84; P=0.082) and 4.04-fold (95% CI, 1.46-11.18; P=0.007) increased odds ratio of rapid GFR decline, respectively.

Conclusion: Among patients with high risk of CV with or without CKD, high CAVI (cut point of ≥ 9) was independently associated with a rapid decline in GFR, suggesting that systemic vascular stiffness predicted a decrease in renal function in this population.