Chronic kidney disease categories and renal–cardiovascular outcomes in type 2 diabetes without prevalent cardiovascular disease: a prospective cohort study (JDDM25)

Aims/hypothesis

In type 2 diabetic patients at low risk for cardiovascular disease (CVD), the relationship between the clinical course of nephropathy by stage of chronic kidney disease (CKD) and onset of CVD remains unclear. Clarification of this relationship is important for clinical decision-making for both low- and high-risk diabetic patients.

Methods

This 4?year prospective study enrolled 2,954 type 2 diabetic patients with no prevalent CVD, and serum creatinine <176.8?μmol/l. The risk for CVD onset (non-fatal and fatal CVD and stroke, and peripheral arterial disease) was assessed according to CKD stage categorised by urinary albumin-to-creatinine ratio (ACR; mg/mmol) and estimated GFR (eGFR; ml?min^?1 1.73?m^?2). Association of progression from ‘no CKD’ stage (ACR <3.5?mg/mmol and eGFR ≥90?ml?min^?1 1.73?m^?2) with risk for CVD onset was also evaluated.

Results

During follow-up (median 3.8?years), 89 CVD events occurred. Compared with patients with ‘no CKD’ as reference, those with ACR?≥?35.0?mg/mmol with co-existing eGFR 60–89?ml?min^?1 1.73?m^?2 or <60?ml?min^?1 1.73?m^?2 showed increased risk for CVD onset, whereas those with eGFR ≥90?ml?min^?1 1.73?m^?2 did not. Those with ACR <3.5?mg/mmol and eGFR <60?ml?min^?1 1.73?m^?2 did not show any increased risk. Among patients with ‘no CKD’ stage at baseline, those who progressed to ACR ≥3.5?mg/mmol during follow-up showed an increased risk compared with those who did not, whereas those who progressed to eGFR <90?ml?min^?1 1.73?m^?2 did not have increased risk.

Conclusions/interpretation

The risk for CVD was associated with progression of albuminuria stage rather than eGFR stage in type 2 diabetic patients at relatively low risk for CVD.     

Histopathological correlates of the napkin-ring sign plaque in coronary CT angiography

ObjectiveThe purpose of this study was to identify histologic characteristics of advanced coronary atherosclerotic plaques that are related with the detection of the napkin-ring sign (NRS) in coronary CT angiography (CCTA).MethodsCCTA was performed in 7 human donor hearts. Histological slicing and stainings were performed in 1 mm increments of each major coronary artery. Histology was co-registered with the CT-data and classified according to the modified AHA classification.ResultsAdvanced plaques (types IV–VI) were present in 139 (23%) of 611 cross sections. Of these 33 (24%) demonstrated an NRS in CCTA. NRS plaques were associated with greater non-core plaque area (median 10.2 vs. 6.4 mm², p < 0.01) and larger vessel area (median 17.1 vs. 13.0 mm², p < 0.01). The area of the necrotic/lipid core was larger in plaques with NRS (median 1.1 vs. 0.5 mm², p = 0.05). Angiogenesis tended to be more frequent in plaques with NRS (48% vs. 30%) whereas micro-calcifications tended to be more frequent in plaques without NRS (27% vs. 46%) (p = 0.06 and 0.07 respectively). In a multivariate analysis, necrotic/lipid core area (OR = 1.9), non-core plaque area (OR = 1.6), and total vessel area (OR = 0.9) independently predicted the appearance of the NRS in coronary CT angiography.ConclusionDelineation of NRS in CCTA is independently linked to the size of the necrotic/lipid core, the size of the non-core plaque and to the vessel area as measured in histology of advanced coronary atherosclerotic plaques.     

Distributions of calcitonin gene-related peptide and substance P in the human maxillary sinus of Japanese cadavers

BackgroundSubstance P (SP) and calcitonin gene-related peptide (CGRP) are released by the nociceptive sensory nerve and are involved in blood flow, pain and inflammation in the nasal mucosa. The purpose of this study was to assess the distribution of the SP and CGRP nerve fibres related to blood supply within human Schneiderian membrane of the maxillary sinus (MS).Material and methodsIn this study, the MS from Japanese cadavers was examined by whole-mount immunohistochemistry. Human male cadavers (ranging in age from 80 to 90 years) were used in this study.ResultsSP- and CGRP-positive fibres were found around large vessels of the medialis superior alveolar branches and also within the floor region of the MS. The floor region of the MS was composed of complex branches of these fibres.ConclusionOur results give useful information for surgical sinus floor elevation in this region of the MS. These anatomical features may assist in the execution of a successful surgical procedure.     

Plasma Level of Homocysteine Associated with Severe Vertebral Fracture in Postmenopausal Women

The aim of this cross-sectional cohort study was to clarify risk factors for severe vertebral fractures in postmenopausal Japanese women. Subjects were ambulatory volunteers age over 50 years who were recruited from a population of outpatients at a primary care institute. At registration, age, body mass index (BMI), bone mineral density (BMD), and present illness were investigated. Biochemical parameters including urinary levels of type I collagen cross-linked N-telopeptides (NTXs), and pentosidine and plasma levels of homocysteine were measured. Values were compared with different fracture grades (grade 0–3). A total of 1,475 postmenopausal women (66.6 ± 9.0 years) were included in the present study. Distributions of vertebral fracture grades were grade 1, 137 cases (9.3 %); grade 2, 124 cases (8.4 %); and grade 3, 162 cases (11.0 %). Age, BMI, BMD, NTX, pentosidine, and homocysteine were significantly associated with vertebral fracture in unadjusted analysis. In addition, a higher prevalence of hypertension was observed in patients with severe fracture. When comparing vertebral fracture grade 0 versus grade 2–3 by multiple regression analysis, pentosidine and homocysteine levels were a significant risk for moderate/severe vertebral fracture (odds ratio [OR] = 1.17, 95 % confidence interval [CI] 1.00–1.38, p = 0.049; OR = 1.22, 95 % CI 1.03–1.46, p = 0.013). Homocysteine levels were also a significant risk when comparing vertebral fracture grade 0 versus grade 3 (OR = 1.27, 95 % CI 1.04–1.58, p = 0.021). Plasma level of homocysteine was an independent risk for severe vertebral fractures.