There are still many patients suffering from ischemic stroke and related disabilities worldwide. To develop a treatment that promotes functional recovery after acute ischemic stroke, we need to elucidate endogenous tissue repair mechanisms. The concept of a neurovascular unit (NVU) indicates the importance of a complex orchestration of cell–cell interactions and their microenvironment in the physiology and pathophysiology of various central nervous system diseases, particularly ischemic stroke. In this concept, microvascular pericytes play a crucial role in regulating the blood–brain barrier integrity, cerebral blood flow (CBF), and vascular stability. Recent evidence suggests that pericytes are also involved in the tissue repair leading to functional recovery following acute ischemic stroke through the interaction with other cell types constituting the NVU; pericytes may organize CBF recovery, macrophage-mediated clearance of myelin debris, intrainfarct fibrosis, and periinfarct astrogliosis and remyelination. In this review, we will discuss the physiological and pathophysiological functions of pericytes, their involvement in the molecular mechanisms underlying tissue repair and functional recovery after ischemic stroke, and a therapeutic strategy to promote endogenous regeneration.

Recently, the Cerebrovascular and Cardiovascular Disease Control Act was enacted, for which it was necessary to establish a comprehensive and accurate nationwide database and promote rational and economical stroke countermeasures in Japan, thus serving the public interest. Among the many studies on stroke registries, the Fukuoka Stroke Registry, a regional cohort, provides highly accurate information, and the Japanese Stroke Data Bank, a nationwide cohort, is highly comprehensive. The findings of these studies have contributed to the construction of evidence and the establishment of guidelines for stroke management. In the Nationwide survey of Acute Stroke care capacity for Proper dEsignation of Comprehensive stroke CenTer in Japan, research on improving the quality of medical care to close the gap between guidelines and clinical practice was performed using electronic medical records. This has enabled the recommendation of medical policies in Japan by visualizing medical care. In the era of healthcare big data and the Internet of Things, plenty of healthcare information is automatically recorded electronically and incorporated into databases. Thus, the establishment of stroke registries with the effective utilization of these electronic records can contribute to the development of stroke care.

Aim: The relationship between handgrip strength (HGS) and clinical outcomes after percutaneous coronary intervention (PCI) has not yet been thoroughly investigated.

Methods: This was a single-center, observational study. A total of 469 patients who underwent PCI and whose periprocedural HGS was measured were included. Patients were divided into two groups: the low HGS group (men, ＜28 kg; women, ＜18 kg) and the high HGS group (men, ≥ 28 kg; women, ≥ 18 kg). The primary outcome was the composite endpoint of all-cause death, myocardial infarction (MI), and heart failure readmission.

Results: There were 151 patients in the low HGS group and 318 patients in the high HGS group. The age of patients in the low HGS group was significantly higher (median [interquartile range]: 78 [71–82] vs. 70 [61–75] years, p＜0.001), while the body mass index and serum albumin level were significantly lower (body mass index: 22.5 [20.2–24.3] vs. 24.3 [22.3–26.6] kg/m², p＜0.001; serum albumin: 3.6 [3.1–3.9] vs. 4.0 [3.7–4.3] g/dL, p＜0.001) than those in the high HGS group. During the median follow-up period of 778 days, the low HGS group had a higher incidence of composite endpoint than the high HGS group (p＜0.001). The low HGS group had a higher risk of all-cause, cardiac, and non-cardiac death (p＜0.001). Multivariable Cox proportional hazards analysis showed that low handgrip strength was an independent predictor for the composite endpoint (hazard ratio 1.80, 95% confidence interval 1.04–3.12, p=0.04).

Conclusions: Low HGS was independently associated with adverse outcomes after PCI.

Aims: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor is a powerful low density lipoprotein cholesterol (LDL-C)-lowering therapy, but this drug is expensive. This study aimed to describe the real-world treatment conditions in patients initiating PCSK9 inhibitor in Taiwan.

Methods: This was a multicenter, retrospective, and observational study. The clinical characteristics, baseline lipid-lowering therapy, and changes in the lipid profile of patients receiving PCSK9 inhibitor treatment were obtained from 11 major teaching hospitals in Taiwan.

Results: A total of 296 patients (age 57±13 years, male 73%) who received PCSK9 inhibitor treatments (73.3% alirocumab and 26.7% evolocumab) from 2017 to 2021 were included. Among the patients, 62.8% had history of coronary artery disease, and 27.7% had myocardial infarction. High intensity statin (HIS) monotherapy or HIS＋ezetimibe treatment was used in 32.5% when initiating PCSK9 inhibitor treatment. Among alirocumab users, 21.2% received 75 mg every 3 to 4 weeks, whereas among evolocumab users, 8.9% received 140 mg every 3 to 4 weeks. Almost all the non-standard-dosing PCSK9 inhibitors were paid by the patients themselves but were not reimbursed by the Taiwan National Health Insurance. Overall, the LDL-C levels at baseline and 12 weeks after treatment were 147.4±67.4 and 69.7±58.2 mg/dL (p＜0.01), corresponding to a 49.6%±31.8% LDL-C reduction.

Conclusions: In the real-world practice in Taiwan, the LDL-C reduction efficacy of PCSK9 inhibitors was slightly lower than that reported in the clinical trials. The use of non-standard-dosing PCSK9 inhibitors was not uncommon in Taiwan.

Aim: Central systolic blood pressure (cSBP) was closely related to hypertension-related organ damage rather than peripheral systolic blood pressure (pSBP). We aimed to estimate cSBP from pSBP without generalized transfer function in normal and Kurosawa and Kusanagi-hypercholesterolemic (KHC) rabbits aged 12 months.

Methods: Two catheter-tip transducers were advanced into the ascending aorta (AA) and distal end of the right brachial artery (Br) through the right common carotid and right radial arteries, respectively, under pentobarbital anesthesia. Pressure waves in response to the intravenous administration of angiotensin II and sodium nitroprusside were simultaneously recorded in AA and Br under regular cardiac pacing.

Results: The first (pSBP) and second peaks (pSBP₂) of the brachial blood pressure and their average (pSBP_m) were significantly correlated with cSBP, despite Murgo’s wave pattern of central pressure waves in both rabbit groups. In Bland–Altman plot and its modification as a function of the peripheral augmentation index (pAI) analyses, the differences between pSBP and cSBP decreased, and those between pSBP₂ and cSBP increased significantly in their average- or pAI-dependent manner, with undeniable mean biases in both rabbit groups. When the same analyses for SBP_m were performed instead, the mean bias was around zero, with reduced variance in the two rabbit groups. The observed pressure or pAI-dependent systematic biases for pSBP and pSBP₂ disappeared, representing the precise feature of pSBP_m as a cSBP estimate.

Conclusions: We conclude that pSBP_m could be more precise than pSBP₂ as a cSBP estimate, irrespective of blood pressure levels, pAI, or the presence of atherosclerosis.

Aim: This study aimed to reveal whether a larger postprocedural minimum lumen area (MLA) would reduce restenosis risk after endovascular therapy (EVT) using drug-coated balloons (DCBs) in femoropopliteal (FP) lesions.

Methods: This retrospective, nonrandomized, single-arm, and multicenter registry analyzed patients with FP lesions undergoing intravascular ultrasound (IVUS)-guided EVT with DCB between 2017 and 2021. The primary outcome was restenosis 1 year after EVT. The association between IVUS-based MLA and restenosis risk was investigated using a generalized propensity score (GPS) method to address imbalance of baseline covariates. The dose–response function of IVUS-measured MLA for restenosis risk was developed using the GPS-adjusted Cox proportional hazards regression model.

Results: This study enrolled consecutive 489 patients with 595 lesions undergoing DCB treatment. The median MLA (interquartile range) was 13.20 (9.90–16.91) mm². Kaplan–Meier estimates showed that freedom from restenosis was 84.4% at 1 year. The GPS-adjusted dose–response function showed that MLA was inversely associated with restenosis risk. The upper limit of 95% confidence interval (CI) of the slope was lower than 0 between 10.6 and 17.0 mm² of MLAs. The 1-year cumulative incidence of restenosis was estimated to be 9.8% (95% CI, 5.8%–13.7%) for the 3rd quartile of MLA (16.91 mm²) versus 18.5% (12.3%–24.1%) for the 1st quartile (9.90 mm²), with a hazard ratio of 0.51 (95% CI, 0.39–0.67; p＜0.001).

Conclusions: The present GPS analysis suggested that larger IVUS-measured MLA might be associated with lower risk of 1-year restenosis after DCB treatment for FP lesions.

Aim: Serum levels of cholesterol absorption and synthesis markers are known to be associated with cardiovascular risk. Familial hypercholesterolemia (FH) is a well-known inherited disorder presenting elevated low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) levels and premature coronary disease. In this study, we aim to examine the differences in terms of serum markers of cholesterol metabolism between FH and non-FH individuals and to examine their associations with serum lipid levels.

Methods: In this study, we utilized data on serum markers of cholesterol metabolism, namely, lathosterol (Latho, synthesis marker), campesterol (Campe, absorption marker), and sitosterol (Sito, absorption marker) measured by gas chromatography of the CACHE consortium, which comprised of 13 research groups in Japan. Clinical data were compiled using REDCap system. Among the 2944 individuals in the CACHE population, we selected individuals without lipid-lowering medications and hemodialysis patients for this CACHE study FH analysis. Multivariable adjustment was performed to assess the associations.

Results: In this study, we analyzed data from 51 FH patients and 1924 non-FH individuals. After adjustment for possible confounders, the FH group was shown to have significantly higher Campe and Sito concentrations and insignificantly higher Latho concentrations than the non-FH group. These marker concentrations showed nonlinear associations with TC in the FH group. Campe/Latho and Sito/Latho ratios were significantly higher in the FH group than in the non-FH group.

Conclusion: FH group had significantly elevated serum Campe and Sito concentrations and insignificantly elevated Latho concentrations; thus, intestinal cholesterol absorption relative to hepatic cholesterol synthesis was suggested to be elevated in patients with FH. Serum Latho, Campe, and Sito concentrations showed nonlinear associations with TC in the FH group.

Aim: Wall shear stress (WSS) is the frictional force caused by viscous blood flowing along the vessel wall. Decreased WSS is associated with local vascular endothelial dysfunction and atherosclerosis. The vector flow mapping (VFM) technique detects the direction of intracardiac blood flow and WSS on the vessel wall with echocardiography. In this study, we examined carotid WSS by applying the VFM technique to the carotid arteries and evaluated its relationship with cerebral small vessel disease (SVD).

Methods: This is a single-center, prospective, observational study. We investigated the association between carotid WSS and SVD imaging, and cognitive outcomes in consecutive 113 patients with acute lacunar infarction.

Results: Carotid WSS was negatively associated with age (r=-0.376, p＜0.001). Lower WSS was correlated with total SVD scores (ρ=-0.304, p=0.004), especially with enlarged perivascular space (EPVS) in the basal ganglia ＞10 (p＜0.001). The carotid intima-media thickness was not associated with the total SVD score (ρ=-0.183, p=0.052). Moreover, lower WSS was associated with executive dysfunction.

Conclusion: EPVS has recently been reported as a marker of early SVD imaging, and executive dysfunction is common in vascular cognitive impairment. These results suggested that decreased carotid WSS based on vascular VFM, which can be measured easily, is associated with imaging and cognitive changes in the early stages of SVD.

Aims: Acute rupture or erosion of unstable atherosclerotic plaques is a major cause of adverse consequences of atherosclerotic cardiovascular disease, often leading to myocardial infarction or stroke. High uric acid (HUA) is associated with the increasing risk of cardiovascular events and death. However, the mechanism by which HUA promotes atherosclerosis and whether HUA affects plaque stability are still unclear.

Methods: We constructed an atherosclerotic Apoe−/− mouse model with HUA. The progression of atherosclerosis and plaques was determined by Oil Red O staining, hematoxylin and eosin (H&E) staining, and Masson staining. TdT-mediated dUTP nick-end labeling assay and immunohistochemistry were used to observe the changes of apoptosis and autophagy in plaques, respectively. Then, we validated the in vivo results with RAW 264.7 cell line.

Results: HUA promoted atherosclerosis and exacerbated plaque vulnerability, including significantly increased macrophage infiltration, lipid accumulation, enlarged necrotic cores, and decreased collagen fibers. HUA increased cell apoptosis and inhibited autophagy in plaques. In vitro results showed that HUA decreased cell viability and increased cell apoptosis in foam cells macrophages treated with oxidized low-density lipoprotein. An activator of autophagy, rapamycin, can partially reverse the increasing apoptosis.

Conclusion: HUA promoted atherosclerosis and exacerbated plaque vulnerability, and HUA facilitates foam cell apoptosis by inhibiting autophagy.

Aim: The relationship between carotid artery ultrasound findings and clinical outcomes in patients who undergo percutaneous coronary intervention (PCI) has not been completely elucidated.

Methods: This single-center retrospective study investigated 691 patients who underwent PCI and carotid ultrasound testing. Maximum carotid intima-media thickness (CIMT) was defined as the greatest CIMT at the maximally thick point among the common carotid artery, carotid bulb, and internal carotid artery. A carotid plaque was defined as vessel wall thickening with a CIMT ≥ 1.5 mm. The characteristics of carotid plaque (heterogeneity, calcification, or irregular/ulcerated surface) were evaluated visually. Patients were divided into those with and without heterogeneous carotid plaque (maximum CIMT ≥ 1.5 mm and heterogeneous texture). The endpoint was the incidence of a major adverse cardiovascular event (MACE) defined as a composite of cardiovascular (CV) death, myocardial infarction, and ischemic stroke.

Results: Among 691 patients, 309 were categorized as having a heterogeneous plaque. Patients with heterogeneous plaques were at a higher risk of MACE than those without (p=0.002). A heterogeneous plaque was independently associated with MACE after adjusting for covariates (hazard ratio [HR], 1.71; 95% confidence interval [CI], 1.01–2.90; p=0.046). Calcified or irregular/ulcerated plaques were correlated with a higher incidence of MACE, but both were not independently associated with MACE (HR, 1.35; 95% CI, 0.69–2.64, p=0.38 and HR, 0.98; 95% CI, 0.57–1.69; p=0.95, respectively).

Conclusion: The presence of a heterogeneous carotid plaque in patients who underwent PCI predicted future CV events. These patients may require more aggressive medical therapy and careful follow-up.

Aims: We aimed to assess the prognostic impact of hyperhomocysteinemia (HHcy) on the recurrent vascular event risk in stroke patients with or without chronic kidney disease (CKD).

Methods: In this prospective observational study, 621 patients (mean age, 69.5 years; male, 62.2%) with ischemic stroke or transient ischemic attack were consecutively enrolled within 1 week of onset and followed-up for 1 year. HHcy was defined as elevated levels of fasting total homocysteine ＞15 µmol/L. CKD was defined as an estimated glomerular filtration rate of ＜60 mL/min/1.73 m² or a history of renal replacement therapy. The primary outcome was a composite of major adverse cardiovascular events (MACEs), including nonfatal stroke, nonfatal acute coronary syndrome, major peripheral artery disease, and vascular death.

Results: The prevalence of HHcy was 18.5%. Patients with HHcy were more likely to have intracranial (37.4% versus 24.8%; p=0.008) and extracranial (20.9% versus 13.0%; p=0.037) artery stenosis than were those without HHcy. At 1 year, patients with HHcy were at a greater risk of MACE than were those without HHcy (annual rate, 17.8% versus 10.4%; log-rank p=0.033). In the Cox proportional hazard regression models, HHcy was independently associated with an increased risk of MACE in patients with CKD (adjusted hazard ratio [HR], 2.06; 95% confidence interval [CI], 1.02-4.20), whereas HHcy was not predictive of MACE in those without CKD (adjusted HR, 1.00; 95% CI, 0.30-3.32).

Conclusions: Elevated levels of serum homocysteine can be an important modifiable risk factor in stroke patients with CKD, but not in those without CKD.

Aim: Cardiovascular disease is a life-threatening chronic kidney disease (CKD) complication. Although cardiovascular risk factor management is significant in patients with CKD, there are few reports that detail the frequency of complications and the treatment of cardiovascular risk factors at different stages of CKD in clinical practice.

Methods: There were a total of 3,407 patients with non-dialysis-dependent CKD who participated in the Fukuoka Kidney disease Registry Study, and they were cross-sectionally analyzed. The patients were classified into five groups based on their estimated glomerular filtration rate and urinary albumin to creatinine ratio according to Kidney Disease: Improving Global Outcomes 2012 guidelines, which recommend low, moderate, high, very high, and extremely high risk groups. The primary outcomes were the cardiovascular risk factor burden and the treatment status of cardiovascular risk factors. Using a logistic regression model, the association between the CKD groups and the treatment status of each risk factor was examined.

Results: The proportion of patients with hypertension, diabetes mellitus, and dyslipidemia significantly increased as CKD progressed, whereas the proportion of patients who achieved cardiovascular risk factor treatment targets significantly decreased. In the multivariable analysis, the odds ratios (ORs) of uncontrolled treatment targets were significantly higher for hypertension (OR 3.68) in the extremely high risk group than in the low risk group.

Conclusions: Patients with non-dialysis-dependent CKD demonstrate an increased cardiovascular risk factor burden with greater severity of CKD. Extremely high risk CKD is associated with difficulty in managing hypertension.

Aims: Complex and high-risk intervention in indicated patients (CHIP) is an emerging concept in the contemporary percutaneous coronary intervention (PCI). CHIP is known to consist three factors, namely, (1) patient factors, (2) complicated heart disease, and (3) complex PCI. However, it remains unclear whether additional CHIP factors further increase the incidence of complications in complex PCI. Thus, in this study, we aim to compare the incidence of complications among definite CHIP, possible CHIP, and non-CHIP in terms of complex PCI and to further investigate the association between CHIP and complications.

Methods: The primary aim of this study was to determine the major complications in PCI. We included 989 PCI lesions and divided those into definite CHIP (n=140), possible CHIP (n=397), and the non-CHIP groups (n=452).

Results: The incidence of major complications was noted to be the highest in the definite CHIP, followed by the possible CHIP, and lowest in the non-CHIP (p=0.001). The multivariate logistic regression analysis using a generalized estimating equation revealed definite CHIP (versus non-CHIP: odds ratio (OR) 2.099, 95% confidence interval (CI) 1.062–4.150, p=0.033) was significantly associated with major complications after controlling for confounding factors. Another multivariate logistic regression analysis revealed immunosuppressive drugs (OR 3.040, 95% CI 1.251–7.386, p=0.014), unstable hemodynamics (OR 5.753, 95% CI 1.217–27.201, p=0.027), and frailty (OR 2.039, 95% CI 1.108–3.751, p=0.022) were significantly associated with major complications among CHIP factors.

Conclusions: The incidence of major complications in complex PCI was determined to be the highest in the definite CHIP, followed by the possible CHIP and lowest in the non-CHIP. Thus, more attention should be given to the three components of CHIP to prevent major complications in complex PCI.

Aim: Patients with end-stage kidney disease (ESKD) have an unparalleled risk of left ventricular hypertrophy (LVH) and vascular calcification (VC), both of which introduce excessive cardiovascular risk. However, it remains unclear whether LVH geometry co-modulates cardiovascular outcomes with VC in this population.

Methods: A retrospective cohort study was conducted. Patients with ESKD requiring chronic hemodialysis were identified from Shin Kong Wu Ho-Su Memorial Hospital between October and December 2018, with echocardiographic LVH geometry and aortic arch calcification (AoAC) determined. They were divided into four groups according to AoAC severity and eccentric or concentric LVH. We used Kaplan–Meier analysis and Cox proportional hazard regression to analyze their cardiovascular and all-cause mortality after multivariate adjustment.

Results: Overall, 223 patients with ESKD with LVH were analyzed, among whom 29.1%, 23.3%, 25.1%, and 22.4% had non-to-mild AoAC with eccentric and concentric LVH and moderate-to-severe AoAC with eccentric and concentric LVH, respectively. After 3.5 years of follow-up, patients with ESKD with moderate-to-severe AoAC and concentric LVH had a significantly higher risk of cardiovascular mortality than those with non-to-mild AoAC and eccentric LVH (hazard ratio 3.35, p=0.002). However, those with moderate-to-severe AoAC but eccentric LVH did not have higher cardiovascular mortality. Similarly, patients with ESKD with moderate-to-severe AoAC and concentric LVH had a significantly higher all-cause mortality than those with non-to-mild AoAC and eccentric LVH, whereas the other two groups did not have higher risk.

Conclusion: LVH geometry could help stratify the risk of patients with ESKD when they had severe VC, and co-existing severe VC and concentric LVH aggravated cardiovascular risk.

Aim: Little is known regarding the association between breakfast type and cardiovascular mortality. We examined the associations between breakfast type and risks of mortality from stroke, coronary heart disease (CHD), and total cardiovascular disease (CVD).

Methods: A total of 85,319 males and females aged 40 to 79 years who were free from CVD and cancers at baseline were involved in this study. The participants were divided into five groups according to their self-reported breakfast types: Japanese breakfast, Western breakfast, mixed Japanese–Western breakfast, other breakfast, and skipping breakfast groups. All hazard ratios (HRs) were estimated using Cox proportional hazards regression models after adjusting for the potential confounding factors.

Results: During the median 19-year follow-up, we identified CVD deaths of 5,870 subjects. Compared to the Japanese breakfast, the multivariable HRs (95% CIs) of total CVD were 0.64 (0.52–0.79) for mixed Japanese–Western breakfast, 0.90 (0.77–1.04) for Western breakfast, 1.24 (0.95–1.61) for other breakfast, and 1.31 (1.00–1.71) for skipping breakfast. The corresponding HRs (95% CIs) of total stroke were 0.67 (0.49–0.91), 0.83 (0.66–1.05), 1.15 (0.76–1.74), and 1.25 (0.82–1.92), and those of CHD were 0.73 (0.48–1.12), 1.08 (0.81–1.44), 1.09 (0.60–1.98), and 1.77 (1.11–2.83).

Conclusion: Compared to Japanese breakfast, mixed Japanese–Western breakfast may have a protective role in cardiovascular mortality whereas skipping breakfast may harm cardiovascular health.

Aim: Some observational studies suggested that atherosclerosis increased the risk of venous thromboembolism (VTE), and vice versa. However, the results were conflicting, and the causal relationship is yet to be established. Therefore, we applied Mendelian randomization (MR) analyses to assess the bidirectional causality between coronary heart disease (CHD) and VTE, deep venous thrombosis (DVT), and pulmonary embolism (PE).

Methods: A total of 184,305 individuals with CHD were included from the CARDIoGRAMplusC4D Consortium. Information on VTE, DVT, and PE were obtained from the FinnGen biobank. Genetic instruments for CHD and VTE were constructed using 37 and 12 single-nucleotide polymorphisms, respectively. Inverse-variance weighted meta-analysis under a random-effect model was used as the preliminary estimate. Five complementary MR methods were also used, including weighted median, MR-Egger, multivariable MR (adjusted for the body mass index), simple mode, and weighted mode methods.

Results: The genetically instrumented VTE (odds ratio [OR]: 1.05; 95% confidence interval [CI]: 1.00–1.11; P=0.06), DVT (OR: 1.03; 95% CI: 0.99–1.08; P=0.19), or PE (OR: 1.07; 95% CI: 0.98–1.16; P=0.11) showed no causal relationships with CHD. There was also no clear evidence showing the causal effects of CHD on VTE (OR: 1.00; 95% CI: 0.82–1.22; P=0.98), DVT (OR: 1.00; 95% CI: 0.79–1.27; P=0.97), or PE (OR: 0.98; 95% CI: 0.82–1.18; P=0.87). No pleiotropic bias was found in the MR analyses. As heterogeneity was significant, a random model was used to minimize the effect of heterogeneity.

Conclusions: No causal associations existed between CHD and VTE. Arterial and venous thromboses may represent separate entities.

Aims: Information is limited about the influence of obstructive sleep apnea (OSA) on developing cardiovascular disease (CVD) among Asian community-dwelling populations. We examined the association between nocturnal intermittent hypoxia as a surrogate marker of OSA and the risk of CVD in a Japanese community-based cohort study.

Methods: We used baseline surveys from 2000 to 2008 to study the cohort data of 5,313 residents from three Japanese communities who were between the ages of 40 and 74 years and initially free from ischemic heart disease and stroke. We assessed the number of 3% oxygen desaturation index (ODI) as the indicator of nocturnal intermittent hypoxia. We divided individuals into two groups depending on 3% ODI (3% ODI ≥ 5 or 3% ODI ＜5). Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for CVD according to 3% ODI. Age, sex, body mass index, alcohol, and smoking were adjusted in the multivariable models.

Results: During 12.8 years of the median follow-up with 66,796 person-years, 185 cases with CVD (115 stroke and 70 coronary heart disease [CHD]) were recorded. The multivariable HRs (95% CIs) were 1.49 (1.09–2.03), 2.13 (1.08–4.22), and 1.93 (1.16–3.19) for the 3% ODI ≥ 5 group versus the 3% ODI ＜5 group of developing CVD, lacunar infarction, and CHD, respectively.

Conclusions: Nocturnal intermittent hypoxia may increase the risk of developing lacunar infarction and CHD among community-dwelling Japanese populations. However, we could not find a significant risk of developing total stroke or stroke subtypes such as intraparenchymal hemorrhage, subarachnoid hemorrhage, and total ischemic stroke.