Transitional medicine refers to the seamless continuity of medical care for patients with childhood-onset diseases as they grow into adulthood. The transition of care must be seamless in medical treatment as the patients grow and in other medical aids such as subsidies for medical expenses in the health care system. Inappropriate transitional care, either medical or social, directly causes poorer prognosis for many early-onset diseases, including primary dyslipidemia caused by genetic abnormalities. Many primary dyslipidemias are designated as intractable diseases in the Japanese health care system for specific medical aids, as having no curative treatment and requiring enormous treatment costs for lipid management and prevention of complications. However, there are problems in transitional medicine for primary dyslipidemia in Japan. As for the medical treatment system, the diagnosis rate remains low due to the shortage of specialists, their insufficient link with generalists and other field specialists, and poor linkage between pediatricians and physicians for adults. In the medical care system, there is a mismatch of diagnostic criteria of primary dyslipidemias between children and adults for medical care expense subsidization, as between The Program for the Specific Pediatric Chronic Diseases and the Program for Designated Adult Intractable Diseases. This could lead some patients subsidized in their childhood to no longer be under the coverage of the aids after transition. This review intends to describe these issues in transitional medicine of primary dyslipidemia in Japan as a part of the efforts to resolve the problems by the Committee on Primary Dyslipidemia under the Research Program on Rare and Intractable Disease of the Ministry of Health, Labour and Welfare of Japan.

Aim: This study aimed to investigate the association between vitamin D deficiency and novel biomarkers of atherogenic dyslipidemia among young adults.

Method: A total of 976 young adults were recruited between 2011 and 2019. Their serum 25(OH)D levels were measured, and lipid profile markers, including low-density lipoprotein cholesterol (LDL-C), low-density lipoprotein triglyceride (LDL-TG), and small-dense low-density lipoprotein cholesterol (sdLDL-C), were assessed as novel biomarkers of atherogenic dyslipidemia. Multivariable linear regression was used to analyze the association between vitamin D levels and lipid profile markers. Odds ratios were calculated to assess the risk of atherogenic dyslipidemia in individuals with serum 25(OH)D levels below 30 ng/mL compared to those with levels above 30 ng/mL. Structural equation modeling (SEM) was employed to explore potential mediation pathways.

Results: The study found a significant association between vitamin D levels and lower levels of LDL-C, LDL-TG, sdLDL-C, non-high-density lipoprotein cholesterol (non-HDL-C), triglycerides, and total cholesterol. Individuals with serum 25(OH)D levels below 30 ng/mL exhibited significantly higher odds ratios for developing atherogenic dyslipidemia in a dose–response pattern compared to those with vitamin D levels above 30 ng/mL. Notably, structural equation modeling (SEM) analysis revealed that vitamin D did not affect atherogenic lipid markers through the mediation of insulin resistance markers or high-sensitivity C-reactive protein.

Conclusion: This study provides evidence of an association between vitamin D deficiency and atherogenic dyslipidemia in young adults. It further highlights that individuals with serum 25(OH)D levels below 30 ng/mL are at a significantly higher risk of developing atherogenic dyslipidemia in a dose–response manner compared to those with higher vitamin D levels. These findings underscore the potential role of vitamin D in dyslipidemia management and emphasize the importance of maintaining sufficient vitamin D levels for cardiovascular health in young adults.

Aim: In patients with end-stage kidney disease (ESKD), it is unclear whether an imbalance between myocardial oxygen supply and demand leads to myocardial injury (MI). This study clarifies the association between the balance of the rate pressure product (RPP), consisting of the systolic blood pressure multiplied by the pulse rate (PR), a marker for myocardial oxygen demand, and hemoglobin (Hb), a marker for oxygen supply, with MI.

Methods: A total of 283 consecutive unselected patients for hemodialysis were enrolled in this retrospective, cross-sectional study, and were divided into four groups according to Hb levels (high or low) and RPP. Potential imbalances between myocardial oxygen supply and demand were defined as patients with simultaneous high RPP and low Hb levels. The odds ratio (OR) for MI, defined as cardiac troponin T (cTnT) of ≥ 0.15 ng/mL was investigated using logistic regression analysis between the four patient groups.

Results: The mean age was 68.7 years, 71.3% were men, and 52.6% had diabetes. The mean Hb level was 9.0 g/dL, and 20.5% of patients were latently diagnosed with MI. The median RPP and cTnT level was 12,144 and 0.083 ng/mL, respectively. When exposed to simultaneous high RPP with low Hb, OR significantly increased compared with that of the well-balanced group (RPP ＜12,500 and Hb ≥ 9.0 g/dL; OR 3.63, p＜0.05). Similar results were obtained in multivariate analysis after adjusting for confounding variables. These associations were enhanced or weakened when the Hb cut-off level became lower (Hb=8 g/dL) or higher (Hb=10 g/dL).

Conclusions: As the myocardial oxygen supply and demand balance in patients with ESKD is potentially associated with MI, appropriate management for blood pressure, PR, and anemia may prevent MI.

Aim: In 2022, the Japan Atherosclerosis Society (JAS) has revised its clinical diagnostic criteria of familial hypercholesterolemia (FH) and adopted the use of definite, probable, possible, and unlikely FH according to the Dutch Lipid Clinic Network (DLCN) FH criteria. However, these strata have not been validated and their impact on coronary artery disease (CAD) is yet to be elucidated.

Methods: In this study, we retrospectively examined the patients with FH aged ≥ 15 years (N=857, male=431) who were admitted to Kanazawa University Hospital between 2010 and 2022. We assessed the prevalence of patients with a pathogenic variant as FH and odds ratio (OR) of CAD among each group determined by the JAS criteria 2022 for adults.

Results: In total, 414, 128, 142, and 173 patients were found to have definite, probable, possible, and unlikely FH, respectively, in this population. The prevalences of patients with a pathogenic variant as FH were 77.1%, 28.7%, 13.0%, and 1.2 %, respectively, among the definite, probable, possible, and unlikely FH patients (P-trend ＜0.001). Compared with the reference group of unlikely FH, patients with definite, probable, and possible FH were noted to have significantly higher adjusted odds of developing CAD (OR, 9.1; 95% confidence interval [CI], 3.2–12.6; P＜0.001 and OR, 4.2; 95% CI, 1.7–6.4; P＜0.001, and OR, 2.8; 95% CI, 1.2–4.4; P=0.002, respectively).

Conclusion: The new JAS diagnostic criteria for FH have been noted to work well in terms of diagnosing definitive, probable, or possible FH patients. Thus, it is seen to be of great help in terms of risk discrimination.

Aims: Coronary vasospasm is associated with acute coronary syndrome (ACS) and may persist during primary percutaneous coronary intervention (PCI). We aimed to elucidate the incidence, morphological characteristics, and prognostic impact of residual vasospasm in plaque rupture (PR) and plaque erosion (PE) lesions using optical coherence tomography (OCT).

Methods: We enrolled 142 patients with ACS who underwent OCT-guided primary PCI. All patients received intracoronary vasodilators before OCT examination. Residual vasospasm was identified as intimal gathering and categorised as polygonal- or wavy- patterned depending on the luminal shape. A wavy pattern was defined as a curved intimal surface line. A polygonal pattern was defined as a lumen with multiple angles. The incidence of major cardiovascular events, defined as death, non-fatal myocardial infarction, stroke, and any revascularization, within 1-year of PCI was identified.

Results: The prevalence of residual vasospasm in PR and PE was 15.1% (13 of 86) and 21.4% (12 of 56), respectively. Wavy pattern was the major shape of the residual vasospasm. Polygonal-patterned lumen was more frequently observed in PR than in PE (38.5 vs. 8.3 %). The polygonal-patterned lumens had significantly larger lipid arcs (257.9 vs. 78.0 °; P＜0.01), and significantly smaller areas (1.27 vs. 1.88 mm²; P=0.05) than wavy-patterned lumens. Residual vasospasm had a prognostic impact on PR but not PE at 1-year of successful primary PCI.

Conclusion: Considerable proportion of ACS including both PR and PE had residual vasospasm with variable morphological feature and different prognostic impact.

Aims: Critical limb ischemia (CLI) is an emerging public health threat and lacks a reliable score for predicting the outcomes. The Age, Body Mass Index, Chronic Kidney Disease, Diabetes, and Genotyping (ABCD-GENE) risk score helps identify patients with coronary artery disease who have cytochrome P450 2C19 (CYP2C19) polymorphism-related drug resistance and are at risk for cardiovascular adverse events. However, its application to CLI remains unknown. In this study, we aim to validate a modified ACD-GENE-CLI score to improve the prediction of major adverse limb events (MALEs) in patients with CLI receiving clopidogrel.

Methods: Patients with CLI receiving clopidogrel post-endovascular intervention were enrolled prospectively in two medical centers. Amputation and revascularization as MALEs were regarded as the outcomes.

Results: A total of 473 patients were recruited, with a mean follow-up duration of 25 months. Except for obesity, old age, diabetes, chronic kidney disease (CKD), and CYP2C19 polymorphisms were significantly associated with MALEs. Using bootstrap regression analysis, we established a modified risk score (ACD-GENE-CLI) that included old age (≥ 65 years), diabetes, CKD, and CYP2C19 polymorphisms. At a cutoff value of 8, the ACD-GENE-CLI score was superior to the CYP2C19 deficiency only, and the conventional ABCD-GENE score in predicting MALEs (area under the curve: 0.69 vs. 0.59 vs. 0.67, p=0.01). The diagnostic ability of the ACD-GENE-CLI score was consistent in the external validation. Also, Kaplan–Meier curves showed that in CYP2C19 deficiency, the ABCD-GENE and ACD-GENE-CLI scores could all differentiate patients with CLI who are free from MALEs.

Conclusions: The modified ACD-GENE-CLI score could differentiate patients with CLI receiving clopidogrel who are at risk of MALEs. Further studies are required to generalize the utility of the score.

Aim: Studies on the relationship between remnant cholesterol (RC) and arterial stiffness (AS) are limited. This study aims to investigate the relationship between RC and AS and to explore RC, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), non-HDL-C, LDL-C/HDL-C, TG/HDL-C, lipoprotein combine index (LCI), and TC/HDL-C, which are lipid parameters most strongly associated with AS.

Methods: A total of 4653 participants from the REACTION (Risk Evaluation of Cancers in Chinese Diabetic Individuals) study were recruited. AS was defined as a brachial–ankle pulse wave velocity of ≥ 1400 cm/s. Multiple logistic regression analyses were performed to detect its association with lipid parameters (RC, TG, TC, HDL-C, LDL-C, non-HDL-C, LDL-C/HDL-C, TG/HDL-C, LCI, and TC/HDL-C).

Results: Logistic regression analysis showed that compared with other traditional or non-traditional lipid parameters, the association between RC and AS was the strongest (odds ratio (OR) 1.59, 95% confidence interval (CI) 1.30–1.95, P＜0.001). In the stratified analysis, RC was significantly associated with AS in both sexes and at any age, as well as blood glucose, blood pressure, and body mass index levels. Besides, RC and AS were still significantly associated when TG＜1.7 mmol/L (OR:1.58, 95% CI: 1.02–2.45, P=0.04), LDL-C ＜3.4 mmol/L (OR:1.32, 95% CI: 1.01–1.73, P=0.041), HDL-C ≥ 1.0 mmol/L (OR:1.67, 95% CI: 1.34–2.08, P＜0.001), or non-HDL-C＜4.1 mmol/L (OR: 1.42, 95% CI: 1.10-1.82, P=0.007) are controlled within the appropriate range.

Conclusion: In conclusion, compared with traditional lipids and lipid ratios, RC is more strongly associated with AS. The association between RC and AS remains significant even when TG, LDL-C, HDL-C, or non-HDL-C levels are controlled within the appropriate range.

Aim: A close relationship exists between resting heart rate (RHR) and obstructive sleep apnea (OSA). Still, the prognostic importance of nighttime RHR in patients with acute coronary syndrome (ACS) with or without OSA remains unclear.

Methods: In this prospective cohort study, OSA was defined as an apnea–hypopnea index of ≥ 15 events/h, and the high nighttime RHR (HNRHR) was defined as a heart rate of ≥ 70 bpm. The primary endpoint was a major adverse cardiovascular and cerebrovascular event (MACCE), including cardiovascular death, myocardial infarction, stroke, ischemia-driven revascularization, or hospitalization for heart failure.

Results: Among the 1875 enrolled patients, the mean patient age was 56.3±10.5 years, 978 (52.2%) had OSA, and 425 (22.7%) were in HNRHR. The proportion of patients with HNRHR is higher in the OSA population than in the non-OSA population (26.5% vs. 18.5%; P＜0.001). During 2.9 (1.5, 3.5) years of follow-up, HNRHR was associated with an increased risk of MACCE in patients with OSA (adjusted HR: 1.56, 95% CI: 1.09–2.23, P=0.014), but not in patients without OSA (adjust HR: 1.13, 95% CI: 0.69–1.84, P=0.63).

Conclusions: In patients with ACS, a nighttime RHR of ≥ 70 bpm was associated with a higher risk of MACCE in those with OSA but not in those without it. This identifies a potential high-risk subgroup where heart rate may interact with the prognosis of OSA. Further research is needed to determine causative relationships and confirm whether heart rate control impacts cardiovascular outcomes in patients with ACS-OSA.

Aims: Blood pressure variability (BPV) was associated with the clinical outcomes in patients with acute ischemic stroke (AIS) due to large-vessel occlusion (LVO) after endovascular treatment (EVT). This study aimed to investigate whether the use of antihypertensive drugs could affect this association in patients with AIS-LVO after EVT.

Methods: We retrospectively screened consecutive patients with AIS-LVO who had successful recanalization after EVT and calculated their systolic BPV (SBPV) during the first 24 h after EVT using eight statistical methodologies based on previously published literature. Poor outcome was defined as a modified Rankin Scale score of 3–6 at 90 days. Logistic regression analysis was performed to assess this association, and different prediction models were constructed to assess the effect of the use of antihypertensive drugs.

Results: A total of 214 patients were finally included, including 92 (43.0%) with good outcomes, and 136 (63.6%) who received antihypertensive drugs. SBPV indicators were significantly lower in patients with good outcomes versus those with poor outcomes. The logistic analysis showed that all SBPV indicators were consistently associated with poor outcomes (odds ratio, 1.031–1.282, all P＜0.05) in all populations, which was confirmed in patients not using antihypertensive drugs. However, no SBPV indicator was found to be associated with poor outcomes in patients using antihypertensive drugs. Receiver operating characteristic curves showed that the area under the curve (AUC) was larger in the model adjusting for antihypertensive drugs (AUC 0.774–0.783) compared with the one not adjusted for antihypertensive drugs (AUC 0.739–0.754).

Conclusion: In the anterior circulation of patients with AIS-LVO who had successful recanalization after EVT, the utilization of antihypertensive drugs may have some impact on the relationship between SBPV and clinical outcomes.

Aim: The concept of risk age may help overcome an excessive weight of age in cardiovascular risk functions. This study aimed to evaluate the equivalence of risk age with arterial stiffness by comparing people with increased risk age and individuals with the same chronological and risk age. In order to materialize this aim, we categorized individuals based on cardiovascular risk and compared groups with increased risk factors (other than age) and groups with normal levels.

Methods: This is a cross-sectional population-level study carried out in Girona province within the context of the REGICOR study (Girona Heart Registry). In this study, individuals aged 35–90 years who had a brachial–ankle pulse wave velocity measurement and with no previous cardiovascular disease or peripheral arterial disease were included. Cardiovascular risk was estimated with the FRESCO (in 35–79 year-olds), SCORE2 (in 35–69 year-olds), and SCORE2-OP (in 70–90 year-olds) functions and categorized to calculate and compare (in each category) the median chronological age in the group with increased risk factors and the reference. Arterial stiffness was assessed with the brachial–ankle pulse wave velocity (baPWV). The analyses were carried out separately by sex.

Results: In this study, 2499 individuals were included, with a mean age of 59.7 and 46.9% of men. Men presented worse health condition, including a higher mean cardiovascular disease risk score. Both men and women with increased levels of risk factors showed worse health condition than the respective men and women with optimal levels. In each risk category, the groups with higher risk age than chronological age (increased risk factors) were similar in baPWV values to the groups with the same chronological and risk ages (reference), who were consistently older.

Conclusions: In categories with the same cardiovascular risk, the arterial stiffness of participants with a higher risk factor burden (increased risk age) matched that of older participants with the rest of the risk factors at optimal levels (same chronological and risk age). These results support the guidelines on the utilization of risk age to explain heightened cardiovascular risk, particularly among individuals in middle age.