Cardiovascular disease (CVD) is the leading cause of death in patients with chronic kidney disease (CKD). Multiple factors account for the increased incidence of cardiovascular morbidity and mortality in patients with CKD. Traditional risk factors for atherosclerosis and arteriosclerosis, including age, hypertension, dyslipidemia, diabetes mellitus, and smoking, are also risk factors for CKD. Non-traditional risk factors specific for CKD are also involved in CVD pathogenesis in patients with CKD. Recently, CKD–mineral and bone disorder (CKD–MBD) has emerged as a key player in CVD pathogenesis in the context of CKD. CKD–MBD manifests as hypocalcemia and hyperphosphatemia in the later stages of CKD; however, it initially develops much earlier in disease course. The initial step in CKD–MBD involves decreased phosphate excretion in the urine, followed by increased circulating concentrations of fibroblast growth factor 23 (FGF23) and parathyroid hormone (PTH), which increase urinary phosphate excretion. Simultaneously, the serum calcitriol concentration decreases as a result of FGF23 elevation. Importantly, FGF23 and PTH cause left ventricular hypertrophy, arrhythmia, and cardiovascular calcification. More recently, calciprotein particles, which are nanoparticles composed of calcium, phosphate, and fetuin-A, among other components, have been reported to cause inflammation, cardiovascular calcification, and other clinically relevant outcomes. CKD–MBD has become one of the critical therapeutic targets for the prevention of cardiovascular events and is another link between cardiology and nephrology. In this review, we describe the role of CKD–MBD in the pathogenesis of cardiovascular disorders and present the current treatment strategies for CKD–MBD.

Aims: We examined whether secondhand smoke exposure in childhood affects the risk of coronary heart disease (CHD) in adulthood.

Methods: In the Japan Collaborative Cohort Study, we analyzed data on 71,459 participants aged 40–79 years, with no history of CHD, stroke, or cancer at baseline (1988–1990) and who completed a lifestyle questionnaire including the number of smoking family members in childhood (0, 1, 2, and 3+ members) and followed them up until the end of 2009. The Cox proportional hazards model was used to calculate the multivariable hazard ratios (HRs) with 95% confidence intervals (CIs) of CHD mortality according to the number of smoking family members in childhood.

Results: During the median 18.9 years’ follow-up, 955 CHD deaths were reported. There was a dose–response relationship between the number of smoking family members at home and CHD mortality among middle-aged individuals (40–59 years); the multivariable HRs (95% CIs) were 1.08 (0.76–1.54) for 1, 1.35 (0.87–2.08) for 2, and 2.49 (1.24–5.00) for 3+ smoking family members compared with 0 members (p for trend=0.03). The association for 3+ smoking family members among the middle-aged group was more evident in men than in women (the multivariable HRs [95% CIs] were 2.97 [1.34–6.58] and 1.65 [0.36–7.52], respectively) and more evident in non-current smokers than in current smokers (the multivariable HRs [95% CIs] were 4.24 [1.57–11.45] and 1.93 [0.72–5.15], respectively).

Conclusions: Secondhand smoke exposure in childhood was associated with an increased risk of CHD mortality in adulthood, primarily in middle-aged men and non-current smokers.

Aims: Thrombin exerts various pathophysiological functions by activating protease-activated receptors (PARs), and thrombin-induced activation of PARs promotes the development of non-alcoholic fatty liver disease (NAFLD). Since heparin cofactor II (HCII) specifically inactivates thrombin action, we hypothesized that plasma HCII activity correlates with the severity of NAFLD.

Methods: A cross-sectional study was conducted. Plasma HCII activity and noninvasive clinical markers of hepatic fibrosis including fibrosis-4 (FIB-4) index, NAFLD fibrosis score (NFS) and aspartate aminotransferase-to-platelet ratio index (APRI) were determined in 305 Japanese patients with type 2 diabetes mellitus (T2DM). The relationships between plasma HCII activity and the clinical markers were statistically evaluated.

Results: Multiple regression analysis including confounding factors showed that plasma HCII activity independently contributed to decreases in FIB-4 index (p＜0.001), NFS (p＜0.001) and APRI (p=0.004). In addition, logistic regression analysis for the prevalence of advanced hepatic fibrosis defined by the cutoff points of the clinical scores showed that plasma HCII activity was the sole and common negative factor for prevalence of advanced hepatic fibrosis (FIB-4 index: p=0.002, NFS: p=0.026 and APRI: p=0.012).

Conclusions: Plasma HCII activity was inversely associated with clinical hepatic fibrosis indices including FIB-4 index, NFS and APRI and with the prevalence of advanced hepatic fibrosis in patients with T2DM. The results suggest that HCII can serve as a novel biomarker for assessment of hepatic fibrosis of NAFLD in patients with T2DM.

Aim: To identify the most differentiated serum lipids, especially concerning particle size and fractions, between Japanese living in Japan and Japanese-Americans in Hawaii, in the absence of possible genetic confounders, and cross-sectionally examine the associated modifiable lifestyle factors.

Methods: Overall, 1,241 (aged 40–59 years) Japanese living in Japan and Japanese-Americans in Hawaii were included. We quantified 130 serum lipid profiles (VLDL 1-5, IDL, LDL 1-6, high-density lipoprotein [HDL] 1-4, and their subfractions) using Bruker’s ¹H-nuclear magnetic resonance spectrometer for the primary outcome. Modifiable lifestyle factors included body mass index (BMI), physical activity, alcohol and smoking habits, and 70 nutrient parameters. We evaluated the different lipids between the groups using partial least squares-discriminant analysis and association between extracted lipids and lifestyle factors using multivariable linear regression analysis.

Results: Concentrations of HDL4, HDL with the smallest particle size, were lower in Japanese than in Japanese-Americans of both sexes. Higher fish-derived omega-3 fatty acid intake and lower alcohol intake were associated with lower HDL4 concentrations. A 1% higher kcal intake of total omega-3 fatty acids was associated with a 9.8-mg/dL lower HDL4. Fish-derived docosapentaenoic acid, eicosapentaenoic acid, and docosahexaenoic acid intake were inversely associated with HDL4 concentration. There was no relationship between country, sex, age, or BMI.

Conclusions: Japanese and Japanese-Americans can be differentiated based on HDL4 concentration. High fish intake among the Japanese may contribute to their lower HDL4 concentration. Thus, HDL particle size may be an important clinical marker for coronary artery diseases or a fish consumption biomarker.

Aim: Several clinical trials using intravascular ultrasound (IVUS) evaluation have demonstrated that intensive lipid-lowering therapy by statin or a combination therapy with statin and ezetimibe results in significant regression of coronary plaque volume. However, it remains unclear whether adding ezetimibe to statin therapy affects coronary plaque composition and the molecular mechanisms of plaque regression. We conducted this prospective IVUS analysis in a subgroup from the CuVIC trial.

Methods: The CuVIC trial was a prospective randomized, open, blinded-endpoint trial conducted among 11 cardiovascular centers, where 260 patients with coronary artery disease who received coronary stenting were randomly allocated into either the statin group (S) or the combined statin and ezetimibe group (S＋E). We enrolled 79 patients (S group, 39 patients; S＋E group, 40 patients) in this substudy, for whom serial IVUS images of nonculprit lesion were available at both baseline and after 6–8 months of follow-up.

Results: After the treatment period, the S＋E group had significantly lower level of low-density lipoprotein cholesterol (LDL-C; 80.9±3.7 vs. 67.7±3.8 mg/dL, p=0.0143). Campesterol, a marker of cholesterol absorption, and oxysterols (β-epoxycholesterol, 4β-hydroxycholesterol, and 27-hydroxycholesterol) were also lower in the S＋E group. IVUS analyses revealed greater plaque regression in the S＋E group than in the S group (−6.14% vs. −1.18% for each group, p=0.042). It was noteworthy that the lowering of campesterol and 27-hydroxycholesterol, but not LDL-C, had a significant positive correlation with plaque regression.

Conclusions: Compared with statin monotherapy, ezetimibe in combination with statin achieved significantly lower LDL-C, campesterol, and 27-hydroxycholesterol, which resulted in greater coronary plaque regression.

Aims: Plasma HDL has evidently increased for decades among Japanese, exclusively in HDL particles containing apoA-I but not A-II. Its metabolic background is yet to be elucidated.

Methods: Trends in plasma lipoproteins were analyzed by examining data on total cholesterol, triglyceride and HDL-cholesterol, which are available in the public database of the National Health and Nutrition Examination Survey of Japan (NHNESJ) and in the clinical data of SRL Co., from 1989 to 2019, estimating cholesterol (C) in non-HDL, VLDL, LDL, and sub-fractions of LDL using the equations by Sampson et al. Food intake and supply data in NHNSJ and in the UN Food and Agriculture Organization were also analyzed in relation to the lipoprotein analysis.

Results: HDL-C levels showed a steady increase in men and women throughout the period as per the data retrieved in NHNSJ and SRL data. It is noted to be higher in women than men (from 46.8 to 52.7, and from 58.4 to 68.3 in mg/dl, respectively). Triglyceride and VLDL-C were higher in men but sex difference was not apparent in non-HDL-C and LDL-C levels, while these parameters slightly decreased in both sexes. The increase in HDL was most prominent in women in the age of 50 - 59 (from 57.0 to 73.4). The age-dependent HDL trend was reversed among women during the study period, as increasing instead of decreasing. This increase in HDL was found to coincide with lowered fish/meat ratio in food intake among Japanese.

Conclusion: Marked increase in plasma HDL among Japanese is age- and sex-dependent and exhibited an apparent paradoxical association with lowered fish/meat ratio in their diet. Further investigation is required to elucidate the background for these findings.

Aim: Epidemiological evidence regarding the relationship between fish and fatty acid intake and carotid intima–media thickness (CIMT) has been limited and inconsistent. The current cross-sectional study investigated this issue using baseline data from the Aidai Cohort Study.

Methods: Study subjects were 2024 Japanese men and women aged 34–88 years. Right and left CIMT were measured at the common carotid artery using an automated carotid ultrasonography device. Maximum CIMT was defined as the largest CIMT value in either the left or right common carotid artery. Carotid wall thickening was defined as a maximum CIMT value ＞1.0 mm.

Results: The prevalence of carotid wall thickening was 13.0%. In men, intake of n-3 polyunsaturated fatty acids (PUFA) was independently positively related to the prevalence of carotid wall thickening, while no associations were found between intake of fish and the other fatty acids and carotid wall thickening or maximum CIMT. In women, intake levels of fish, n-3 PUFA, eicosapentaenoic acid, docosahexaenoic acid, and arachidonic acid were independently inversely associated with carotid wall thickening and intake levels of fish, n-3 PUFA, α-linolenic acid, n-6 PUFA, and linoleic acid were independently inversely associated with the maximum CIMT. No significant relationships were found between intake of total fat, saturated fatty acids, or monounsaturated fatty acids and carotid wall thickening or maximum CIMT regardless of sex.

Conclusions: In women, higher intake of fish and n-3 and n-6 PUFA may be associated with a lower prevalence of carotid wall thickening and a decrease in maximum CIMT.

Aim: The aim of this study was to investigate the effects of continuous cilostazol use on emergency department (ED) visits, hospitalizations, and vascular outcomes in patients with hemodialysis (HD) with peripheral artery disease (PAD).

Methods: This retrospective cohort study recruited 558 adult patients, who had received chronic HD for at least 90 days between January 1, 2008 and December 31, 2012, from the National Health Insurance Research Database. Eligible patients were divided into two groups based on continuing or discontinuing cilostazol treatment. Outcome measures were ED visits, hospitalizations, mortality, and vascular outcomes such as percutaneous transluminal angioplasty, surgical bypass, lower leg amputation, ischemic stroke, hemorrhagic stroke, and cardiovascular events.

Results: Patients with continuous cilostazol use had significantly higher prevalence of stroke, cancer, vintage, and the use of angiotensin receptor blocker and β-blocker, but significantly lower incidence of ischemic stroke and cardiovascular events, as well as lower mortality, than those without continuous cilostazol use (all p＜.05). Continuous cilostazol use was independently associated with lower risk of ED visits, hemorrhagic stroke, and cardiovascular events (adjusted hazard ratios: 0.79, 0.29, and 0.67; 95% confidence intervals: 0.62–0.98, 0.10–0.84, and 0.48–0.96, respectively; all p＜.05). Continuous cilostazol use was significantly associated with higher ED visit-free and cardiovascular event-free rates (log-rank test; p＜.05).

Conclusion: Continuous treatment of cilostazol in patients with HD with PAD significantly decreases the risk of ED visits, hemorrhagic stroke, and cardiovascular events and improves ED visit-free and cardiovascular event-free rates during long-term follow-up.

Aims: Few studies have investigated the subclinical atherosclerotic changes in the brain and carotid artery, and in East Asian populations. We sought to investigate whether gravidity, delivery, the age at menarche and menopause and estrogen exposure period are associated with subclinical atherosclerosis of the brain and carotid arteriopathy.

Methods: This cross-sectional study formed part of a cohort study of Ohasama residents initiated in 1986. Brain atherosclerosis and carotid arteriopathy were diagnosed as white matter hyperintensity (WMH) and lacunae evident on brain magnetic resonance imaging (MRI) and carotid intimal media thickness (IMT) or plaque revealed by ultrasound, respectively. The effect of the reproductive events on brain atherosclerosis and carotid arteriopathy was investigated using logistic regression and general linear regression models after adjusting for covariates.

Results: Among 966 women aged ≥ 55 years in 1998, we identified 622 and 711 women (mean age: 69.2 and 69.7 years, respectively) who underwent either MRI or carotid ultrasound between 1992–2008 or 1993–2018, respectively. The highest quartile of gravidity (≥ 5 vs. 3) and delivery (≥ 4 vs. 2), and the highest and second highest (3 vs. 2) quartiles of delivery were associated with an increased risk of WMH and carotid artery plaque, respectively. Neither of age at menarche, menopause, and estrogen exposure period estimated by subtracting age at menarche from age at menopause was associated with atherosclerotic changes of brain and carotid arteries.

Conclusions: Higher gravidity and delivery are associated with subclinical atherosclerosis of the brain and carotid plaque.

Aim: Sampson et al. proposed a method to calculate small dense low-density lipoprotein-cholesterol (sdLDL-C) concentrations using common lipid measurements, but its accuracy remains unresolved. We examined the difference between Sampson’s equation and direct measurement in patients with diabetes.

Methods: sdLDL-C was measured directly by our established homogeneous assay and estimated by Sampson’s equation in patients with diabetes (n=1542) and healthy control subjects (n=673). Large-buoyant (lb)LDL-C was estimated using triglycerides and LDL-C, and sdLDL-C was obtained by subtracting lbLDL-C from LDL-C. The effect of fasting/nonfasting state or lipid-lowering drug therapy on sdLDL-C values was also examined in 30 and 43 patients with diabetes, respectively.

Results: The coefficient of determination (R²) between calculated sdLDL-C and direct measurement was 0.73 and 0.61 for healthy controls and patients with diabetes, respectively. The R² between calculated sdLDL-C and nonHDL-C or apolipoprotein B was 0.64 and 0.65, respectively. Calculated sdLDL-C was 4–5 mg/dl or 17%–18% higher than the direct measurement. The lower the plasma lipids, especially sdLDL-C, the greater the dissociation between the two methods. Sampson sdLDL-C was also found to give a positive bias when calculated for the nonfasting samples. Statins and pemafibrate significantly reduced sdLDL-C, but their therapeutic effect was underestimated by 5 mg/dl (24%) via Sampson’s equation.

Conclusions: The correlation between Sampson’s equation and direct measurements of sdLDL-C was reduced in patients with diabetes. Furthermore, the correlations with nonHDL-C and apolipoprotein B were even higher than those with direct sdLDL-C. The accuracy of Sampson’s equation decreased with lower sdLDL-C concentrations and was also influenced by diet.

Aims: Coronary calcification detected by coronary angiography is a simple risk marker for long-term clinical outcomes in stable coronary artery disease. However, the significance of angiographic coronary calcification in the culprit lesion of acute myocardial infarction (AMI) has not been fully discussed. The purpose of this retrospective study was to assess the usefulness of angiographic coronary calcification as a risk marker for long-term clinical outcomes following percutaneous coronary intervention to the culprit lesions of AMI.

Methods: We included 1209 patients with AMI and divided them into the none–mild calcification group (n=923) and the moderate–severe calcification group (n=286) according to angiographic coronary calcification in the culprit lesion of AMI. The primary endpoint was the occurrence of major adverse cardiac events (MACE), which was defined as a composite of all-cause death, nonfatal MI, readmission for heart failure, and ischemia-driven target vessel revascularization.

Results: The median follow-up duration was 542 (Q1: 182, Q3: 990) days. A total of 345 MACE were observed during the study period. The occurrence of MACE was significantly greater in the moderate–severe calcification group than in the none–mild calcification group (43.4% vs. 23.9%, p＜0.001). In the multivariate Cox hazard model, moderate–severe calcification was significantly associated with MACE (hazard ratio 1.302, 95% confidence interval 1.011–1.677, p=0.041) after controlling multiple confounding factors.

Conclusions: Angiographically moderate to severe calcification in AMI culprit lesion was associated with long-term worse clinical outcomes. Angiographic coronary calcification can be a simple risk marker in patients after AMI.

Aims: Whether the multi-dimensional data of serially measured blood pressure contains information for predicting the future risk of death in elderly individuals in nursing homes is unclear.

Methods: Of the elderly individuals staying in a nursing home, 19,740 and 40,055 individuals with serially measured blood pressure from day 1 to 365 (for AI-long) and 1 to 90 (for AI-short) along with the death information at day 366 to 730 and 91-365 were included. The neural network-based artificial intelligence (AI) was applied to find the relationship between BP time-series and the future risks of death in both populations.

Results: AI-long found a significant relationship between the serially measured BP from day 1 to day 365 days and the risk of death occurring 366-730 days with c-statistics of 0.57 (95% CI: 0.51-0.63). AI-short also found a significant relationship between the serially measured BP from day 1 to day 90 and the rate of death occurring 91-365 days with c-statistics of 0.58 (95%CI: 0.52-0.63).

Conclusion: Our results suggest that neural network-based AI could find the hidden subtle relationship between multi-dimensional data of serially measured BP and the future risk of death in apparently healthy elderly Japanese individuals under nursing care.

Aims: The role of cilostazol after intracranial or extracranial artery stent implantation is still unclear. Therefore, we designed this trial to explore the efficacy and safety of cilostazol in this particular population.

Methods: In this retrospective study, patients were divided into the cilostazol or clopidogrel group by the antiplatelet therapy received after artery stent implantation. The primary efficacy endpoint was ischemic stroke. Bleeding events and other antiplatelet drug-related adverse reactions (ADRs) were also recorded. Neurological function prognosis was evaluated by the modified Rankin Scale (mRS) after discharge.

Results: A total of 156 patients were enrolled; 56 underwent intracranial artery stenting, 95 underwent extracranial artery stenting, and 5 underwent intracranial combined with extracranial artery stenting. Any stroke and bleeding events in the hospital of the two groups were comparable (P=0.38, P=0.34, respectively). The incidence of stroke recurrence tended to be lower in the cilostazol group, although not significant (cilostazol vs. clopidogrel, 1.35% vs. 4.88%, P=0.25). There was a significant difference of any bleeding events between the two groups (cilostazol vs. clopidogrel, 5.41% vs. 20.73%, P=0.02). During follow-up, we did not observe an apparent increase of ADRs in the cilostazol group (cilostazol vs. clopidogrel, palpitation 4.05% vs. 2.44%, P=0.58; gastrointestinal discomfort events 8.11% vs. 12.20%, P=0.80). There were no differences between the two groups of neurological function prognosis (P=0.29).

Conclusions: Cilostazol-based dual antiplatelet therapy could be recommended as an effective and safe therapy regimen among patients undergoing intracranial or extracranial artery stent implantation.

Aim: Impaired lung function is associated with atherosclerotic vascular events. Carotid intima-media thickness (cIMT) is a marker for subclinical atherosclerosis. However, few studies have examined the association between lung function and cIMT among never smokers or individuals stratified by age. We investigated the association between lung function and cIMT in the Japanese population.

Methods: We conducted a cross-sectional study of 3,716 men and 8,765 women aged 20 years or older living in Miyagi Prefecture, Japan. Lung function was evaluated using forced expiratory volume at 1 s (FEV₁) and forced vital capacity (FVC) was measured using spirometry. The maximum common carotid artery was measured using high-resolution B-mode ultrasound. An analysis of covariance was used to assess associations between lung function and cIMT and adjusted for potential confounders. A linear trend test was conducted by scoring the categories from 1 (lowest) to 4 (highest) and entering the score as a continuous term in the regression model.

Results: After adjusting for potential confounders including passive smoking, lower FEV₁ and FVC were associated with higher cIMT in both men and women (P＜0.001 for linear trend). This association was confirmed even when we restricted our study to never smokers. Furthermore, even when we stratified by age, an inverse association between lung function and cIMT was confirmed in middle-aged (40–64 years) and elderly participants (65–74 years).

Conclusions: Lower lung function was associated with higher cIMT in the Japanese population independent of age and smoking. Assessment of atherosclerosis or lung function may be required for individuals with lower lung function or atherosclerosis.

Aim: Irisin, an exercise-induced myokine, is a potential neurotrophic factor; however, its relationship with cerebral small vessel disease (CSVD) remains unknown. Therefore, we investigated whether serum irisin levels are associated with CSVD in healthy Japanese men.

Methods: We analyzed data from 720 men free of stroke and participated in this observational study. Serum irisin levels were measured by enzyme-linked immunosorbent assay. CSVD was assessed on deep and subcortical white matter hyperintensities (DSWMHs), periventricular hyperintensities (PVHs), lacunar infarcts (LIs), and cerebral microbleeds (CMBs) on brain magnetic resonance imaging. We calculated the total CSVD score (ranges 0–4) to express the total CSVD burden. We computed the adjusted odds ratios (ORs), with 95% confidence intervals (CIs), of the total CSVD score and individual CSVD features using logistic regression models according to the quartiles of irisin (reference: Q1).

Results: Serum irisin levels were associated with lower ORs of higher (vs. zero or lower score) total CSVD score, with the lowest risk (OR, 0.63; 95% CI, 0.41–0.97) being observed in Q3 compared to Q1 after adjustment of potential covariates. Similar results were obtained for younger adults (＜65 years). Among individual CSVD features, irisin was associated with a reduced risk of LIs in the total sample and PVHs, LIs, and CMBs in younger adults. No relationship was observed in older adults (≥ 65 years).

Conclusions: Serum irisin levels were associated with less burden of total CSVD in healthy Japanese men. Serum irisin levels were also related with a reduced risk of PVHs, LIs, and CMBs, but not DSWMHs.

Aim: The dual-antiplatelet therapy (DAPT) score is recommended for predicting the risk of ischemia and bleeding for patients undergoing percutaneous coronary intervention (PCI). This study aimed to investigate the long-term prognostic value of the DAPT score in older PCI patients.

Methods: This study enrolled 10,724 consecutive patients who underwent PCI from January 2013 to December 2013 in Fu Wai hospital, among whom 2,981 (27.8%) were aged ≥ 65 years. The ischemic endpoint was major adverse cardiovascular and cerebrovascular events (MACCE, including myocardial infarction, all-cause death, and stroke). The bleeding endpoint was Bleeding Academic Research Consortium (BARC) 2, 3, or 5 bleeding.

Results: After a 5-year follow-up, 256 (12.0%) MACCEs and 53 (2.5%) BARC 2, 3, or 5 bleeding occurred. The patients were divided into two groups according to the DAPT score: the low-score (＜2, n=1,646) and high-score (≥ 2, n=485) group. Multivariate Cox regression revealed that the risk of MACCE was similar between the two groups [hazard ratio (HR): 1.214, 95% confidence interval (CI): 0.916–1.609, P=0.178], whereas the risk of bleeding was significantly higher in the high-score group than in the low-score group (HR: 2.447, 95% CI: 1.407–4.257, P=0.002). The DAPT score did not show prognostic value in MACCE [area under the receiver operating characteristic curve (AUROC), 0.534; 95% CI: 0.496–0.572, P=0.079]; however, it demonstrated a certain prognostic value in BARC 2, 3, or 5 bleeding (AUROC, 0.646; 95% CI: 0.573–0.719, P＜0.001).

Conclusion: This study suggested that in older PCI patients, the DAPT score did not show predictive value for MACCE; however, it had a certain predictive value for 5-year BARC 2, 3, or 5 bleeding.

Lecithin–cholesterol acyltransferase (LCAT) plays a significant role in the progression from premature to mature high-density lipoprotein (HDL) in circulation. Consequently, primary or secondary LCAT deletion or reduction naturally results in low serum HDL cholesterol levels. Recently, rare cases of acquired HDL deficiency with LCAT autoantibodies have been reported, mainly from Japan, where LCAT autoantibodies of immunoglobulin G (IgG) caused the HDL deficiency. Here to our knowledge, we report for the first time two cases of acquired HDL deficiency caused by IgG4 linked LCAT autoantibodies with or without a high serum IgG4 level. Furthermore, these cases can extend to a new concept of “IgG4 autoimmune disease” from the viewpoint of verifying the serum autoantibody and/or renal histopathology.