The association of family history of premature cardiovascular disease or diabetes mellitus on the occurrence of gestational hypertensive disease and diabetes

Background: Gestational hypertensive diseases (GHD) and gestational diabetes mellitus (GDM) increase the risk of cardiovascular disease (CVD) later in life. However, the association between gestational medical diseases and familial history of CVD has not been investigated to date. In the present study, we examined the association between familial history of CVD and GHD or GDM via reliable questionnaires in a large cohort of registered nurses. Methods: The Korean Nurses' Survey was conducted through a web-based computer-assisted self-interview, which was developed through consultation with cardiologists, gynecologists, and statisticians. We enrolled a total of 9,989 female registered nurses who reliably answered the questionnaires including family history of premature CVD (FHpCVD), hypertension (FHH), and diabetes mellitus (FHDM) based on their medical knowledge. Either multivariable logistic regression analysis or generalized estimation equation was used to clarify the effect of positive family histories on GHD and GDM in subjects or at each repeated pregnancy in an individual. Results: In this survey, 3,695 subjects had at least 1 pregnancy and 8,783 cumulative pregnancies. Among them, 247 interviewees (6.3%) experienced GHD and 120 (3.1%) experienced GDM. In a multivariable analysis adjusted for age, obstetric, and gynecologic variables, age at the first pregnancy over 35 years (adjusted OR 1.61, 95% CI 1.02-2.43) and FHpCVD (adjusted OR 1.60, 95% CI 1.16-2.22) were risk factors for GHD in individuals, whereas FHH was not. FHDM and history of infertility therapy were risk factors for GDM in individuals (adjusted OR 2.68, 95% CI 1.86-3.86; 1.84, 95% CI 1.05-3.23, respectively). In any repeated pregnancies in an individual, age at the current pregnancy and at the first pregnancy, and FHpCVD were risk factors for GHD, while age at the current pregnancy, history of infertility therapy, and FHDM were risk factors for GDM. Conclusions: The FHpCVD and FHDM are significantly associated with GHD and GDM, respectively. Meticulous family histories should be obtained, and women with family histories of these conditions should be carefully monitored during pregnancy. © 2016 Choi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

관동맥 스텐트 재협착조직내의 세포외 기질의 축적 증가

Department of Medicine/석사[한글] 연구배경: 관동맥질환의 중재적치료술로 도입된 스텐트시술은 기존의 풍선성형술에 비하여 재협착율을 감소시키며 임상적 결과를 호전시킴으로써 그 시술이 점차 증가되는 추세이나, 스텐트재협착율 역시 15-30%에 달하고 있다. 그간의 연구에 의하면 스텐트재협착의 기전은 혈관이나 스텐트의 반동(recoil)에 의한 협착은 경미한데에 비하여, 스텐트내부로의 새로운 신생내막의 침입이 중요한 기전으로 알려져 있으나, 아직 병태생리학적 기전은 잘 알려져 있지 않다. 본 연구의 목적은 관동맥 스텐트 재협착조직의 세포 및 세포외 기질의 병리학적 성분 분석을 통하여 스텐트 재협착기전을 이해하고자 하였다. 연구방법: 관동맥에서 Palmaz-Schatz tm텐트시술후 생성된 스텐트 재협착조직 29표본(스텐트시술 후 평균 5.7개월: 0.5-23개뭘)을 25명의 환자(남/여 18/7; 59±13세)에서 경피적동맥경화반제거술(DCA)을 이용하여 얻은후 조직병리학적 분석을 하였다. 조직병리학적인 분석은 H & E 염색, modified Movat 염색을 통하여 세포의 특징 및 밀도, 세포외 기질의 특징을 분석하였으며, 면역항체를 이용한 면역조직화학염색을 통하여, 세포의 성분(α-actin양성 평활근세포, CD68양성 탐식세포)과 세포외 기질성분으로 hyaluronan 및proteoglycan (versican, biglycan, perlecan), fibrin (T2Gl항체 및 AD1350항체)을 분석하고,Ki67 핵항원 및 PCNA에 대한 항체를 이용하여 세포의 증식율을 측정하였으며, TGF-β1의 발현여부를 조사하였다 연구결과: myxoid tissue가 69%의 조직표본에서 관찰되었는데, 스텐트 시술후 시간경과에 따라서 감소하는 경향을 보였다. 이러한 myxoid tissue를 구성하는 세포외기질로는 versican과 hyaluronan이 풍부하였다. 저세포밀도부위 (48-320/mm**2 )가 59%의 조직표본에서 관찰되었는데 이는 스텐트시술후 4개월 이전에 비하여 4개월 이후에 더 빈번하게 관찰되었다 (4/13 vs 13/16, p<0.01). 이러한 저세포밀도부위를 구성하는 세포외 기질은 주로 collagen (9예) 또는 proteoglycan (1예)으로 두가지 종류 모두 관찰된 예가 6예이었다. 26예의 표본을 Ki67 핵항원염색 결과 16예 (62%) 에서 음성이었으며, 8예는 1% 미만의 양성율을 보였으며, 최대치는 4%이었다. perlecan은 세포주위의 기질에서 염색되었으며, biglycan은 collagen이 주된 저세포밀도부위에서 collagen과 동일 부위에 국한되는 경향이 약 3분의 2예에서 관찰되었다. fibrin염색은 T2G1염색에서 29%, ADI350염색에서 50%의 표본에서 염색되었고, TGF-β1은 조사한 20예중 16예(80%)에서 양성을 보였는데 주로 세포내기질에서 발현되었으며, 2예에서는 세포외 기질에서도 관찰할 수 있었다.Ruthenium red로 염색된 proteoglycan은 전자현미경에서도 확인되었다. 결론: 본 연구결과 스텐트재협착은 세포의 증식보다는 증가된 세포외기질의 축적이 중요한 기전으로 작용할 가능성이 있으며, hyaluronan/versican이 풍부한 hygroscopic matrix를 함유하는 이러한 재협착조직을 풍선성형술로 치료함은 일시적인 조직의 압축을 유발함으로써 치료적 효과를 기대하기는 어려울 것으로 사료된다. [영문] Background Neointimal ingrowth rather than stent recoil is thought to be important for coronary arterial in-stent restenosis. However only limited pathologic data are available to address the mechanisms of in-stunt restenosis. With the specific aim of measuring cell replication rate and of assessing cellularity and extracellular matrix (ECM) composition, we analyzed atherectomized coronary areterial in-stent restenotic specimens. Methods and Results In the present study, we analyzed 29 atherectomized coronary arterial in-stent restenotic tissue samples (14 LAD, 10 RCA, and 5 LCX) retrieved from 25 patients (m/f: 18/7; age 59±13 yr) at 0.5-23 (mean 5.7) months after deployment of Palmaz-Schatz stent. Histopathologic analysis of cellular composition and ECM was performed using H&E, modified Movat pentachrome, and immunocytochemical staining. Cellular proliferation rate, as estimated by use of antibodies to Ki-67 nuclear antigen showed low proliferation rate with the range of 0-4%, and no positive cells were found in 62% of cases. Myxoid tissue having ECM enriched with versican and hyaluronan was found in 69% of cases, and decreased over time after stenting, Foci of cell poor areas were found in 57% of cases, and could be classified into as: (1) containing collagen-rich ECM and (2) containing a proteoglycan rich ECM. Versican, biglycan, perlecan, and hyaluronan were identified with varying individual distributions in the proteoglycan rich area. Specimens with foci of cell poor area tended to increase over time after stenting (31% in <4 mo vs 81% in ≥4mo after stenting, p<0.01). α-smooth muscle actin staining identified the majority of cells as smooth muscle cells (SMCs) and occasional macrophages (712 cells per section) were detected by CD68 antibody. The nature of the ECM was confirmed by electron microscopic study, and shown to be enriched in ruthenium red positive proteoglycans. Positive TGF-β1 staining, mostly intracytoplasmic, was found in 80% of cases. Conclusions These data suggest that enhanced ECM accumulation rather than cell proliferation may be important mechanism for stent restenosis. Angioplasty of stent restenosis may therefore foil due to transient compression of this hygroscopic matrixrestrictio

Prognostic impact of early ST-segment resolution and biochemical markers in patients with ST-elevation myocardial infarction

[No abstract available

(A) pulsed doppler echocardiographic study of ventricular diastolic function in patients with mycardial infraction

의학과/석사[한글] 심근경색증 환자에서는 심실의 수축기능이상 뿐만 아니라 확장기능이상이 동반되 며 이러한 심실 확장기능의 장애는 수축기능이상의 정도에 관계없이 일어날 수 있어 심실확장기능의 측정은 심실기능확장의 조기 평가자료로서 이용되고 있다. 저자는 33명의 심근경색증 환자군(전벽 경색군 20명, 하벽경색군 13명)과 20명의 정상대조군을 대상으로 간헐파도폴러 심초음파검사를 이용하여 좌우심실 유입구에서 심실혈류곡선을 기록하여 심실의 확장기능을 평가하였다. 또한 급성 심근경색증 환자에서 시간경과에 따라 확장기능에 변화가 있는지를 관찰하고, 또한 간헐파도폴러 심초음파검사상의 좌심실 확장기능지표가 심도자술로 측정한 죄심실 확장기말압과 어떠한 상관성이 있는지를 밝히고자 전향적으로 본 연구를 시행하였다. 간헐파도플러 심초음파검사로 기록된 좌우심실 혈류유입속도 분광상을 얻어 초기 심실확장기 최고혈류유입속도(B), 심방수축시 최고혈루유입속도(A), A/E비와 교정압력반감시기를 구하고, phono cardiogram을 이용하여 고정등용적 이완시기를 구하였으며, E곡선과 A곡선 및 확장기 초기 1/3시기에 해당하는 곡선에서 가상의 직선을 그어 기저선과 만나는 면적을 총 면적에 대한 백분율을 구해 각각 E area fraction, A area fraction, 0.33 area fraction이라고 하여 각 환자군과 대조군을 비교하였다. 12명의 급성심근경색증 환자에서는 발병 후 3일 이내(1기), 2주 전우(2기)와 4주 이후(3기)에 추적검사를 하여 좌우심실에서 확장기능지표변화가 있는지를 관찰하였으며, 11멍의 환자에서는 간헐파도폴러 심초음파검사상의 확장기능지표와 심도자술을 이용한 좌심실확장기말압과의 상관관계를 조사하여 다음과 같은 결과를 얻었다. 1. 좌심실의 A 와 E는 환자군과 대조군간의 차이는 없었으나 A/E비 전벽 경색군(,1.04±0.18)과, 하벽 경색군 (1.07±0.23)이 대조군(0.64±0.10)보다 의의있개 높았다(각각 P<0.05). 교정 등용적 이완시기는 전벽 경색군(2.34±0.60√ms)과 하벽 경색군(2.43±0.70 √MS)이 대보군(1.83±7.31√MS)보다 연장되어 있었으며(각각 P<0.05), 0.33 area fraction과 E area fraction은 전벽경색군 (45±7%, 55±5%)과 하벽 경색군(43±9%, 53±8%)이 대조군(59±9%, 67±5%)보다 감소되어 있었고(각각 P<0.05), A area fraction은 전벽 경색군 대조군(43±6%)과 하벽 경색군(47±8%)이 대조군(33±5%)보다 증가하였다(각각 P<0.05). 2. 우심실의 E는 환자군과 대조군간의 차이는 없었으나, A는 하벽경색군 (0.44±0.09 m/s)이 전벽 경색군 (0.36±0.10 m/s)과 대조군(0.28±0.05 m/s)보다 높았다(각각 P<0.05). A/E비는 전벽경색군(0.86±0.23)과 하벽경색군 (1.01±0.19)이 대조군(0.62±0.10)보다 증가하였다(각각 P〈O.05). 0.33 area fraction 과 E area fraction은 전벽 경색군(43±7%, 52±5%)과 하벽 경색군(42±7%, 50±10%)이 대조군(56±9%, 63±7%)보다 감소되어 있 었으며(각각 P<0.05), A area fraction은 전벽 경색군(48±10%)과 하벽경색군 (49±7%)이 대조군 (37±7%) 보다 증가되어 있었다 (각각P〈 0.05.) 3. 12명의 급성 심근경색증 환자의 좌심실측 추적검사에서 A/E비는 1기 1.07±0.22, 2기 0.86±0.17, 3기 0.83±0.21)로 1기에 비하여 2기와 3기에서 감소하였으며(각각 P<0.05), 0.33 area fraction 과 E. area fraction 은 각각 1기에 43±8%, 49±9%, 2기에 53±10%, 59±8%, 3기에 55±9%, 59±7%로 1기에 비하여 2기와 3기에서 증가되었고(각각 P<0.05), A area fraction은 1기에 49±11%, 2기에 39±8%, 3기에 39±8%로 1기에 비하여 2기와 3기에서 감소하였다(각각 P<0.05). 이러한 지표들은 2기 와 3기간에는 차이가 없었다. 4. 12명의 급성 심근경색증 환자의 우심실측 추적검사에서 A는 1기 0.46±0.09(m/s), 2기 0.35±0.10(m/s), 3기 0.31 ±0.06(m/s)로 1기에얘 비하여 2기와 3기에서 감소되었으며 (각각 P<0.01), A/E비는 1기 1.10±0.19, 2기 0.92±O.26, 3기 0.78±0.18로 1기에 비하여 2기와 3기에서 감소되었다(각각 P<0.05, p<0.01), 0.33 area fraction과 E area fraction은 각각 1기에 41±10%, 49±8%, 2기에 49±11%, 53±10%, 3기에 50±7%, 58±8%로 1기에 비하여 2기와 3기에서 증가하였으며(각각 P<0.05), A area fraction은 1기에 50±7 %, 2기에 47±9%, 3기에 42±9%로 1기에 비하여 2기와 3기 애서 증가하였다(각각 P<0.01). 이러한 지표들은 2기와 3기간에는 차이가 없었다. 5. 11명의 심근경색증 환자에서 심도자술로 측정한 좌심실확장기말기압은 비슷한 시기에 측정한 간헐파도폴러 심초음파검사의복장기능지표인 좌심실측의 A/E비(r=0.76, p=0.01), 0.03 area fraction(r=-0.71, P=O.02), 및 E area fraction(r=-0.71, P=0.02)과 높은 상관관계를 보였다. 이상의 결과로 심근경색증 환자에서 전벽 및 하벽 경색군에서 모두 좌심실 및 우심실 확장기능의 이상을 관찰할 수 있었으며, 급성 심근경색증 환자에서 심실 확장기능의 호전이 발병 후 조기 2주 전후에 관찰할 수 있었고, 도플러 심초음파검사상 확장기능의지표인 A/E비, 0.33 area fraction, E area fraction등은 심실확장기 말압과 높은 상관관계를 보였다. [영문] Inflow characteristics of left and right ventricular filling were assessed in 33 patients with myocardial infarction and 20 normal subjects by pulled doppler echocardioraphy, The presence of left and right ventricular diastolic functional change in accordance to the infarct loation, serial change of left and right ventricular diastolic function in patients with acute myocardial infarction, andp correlation between left ventricular end-diastolic pressure and doppler echocardiographic indices function were asaessed. Patients with myocardial infarction were subdivided into two groups, anterior infarction group(20 patients) and inferiorin farction group(13 patient 7), according to the site of involved myocardium. Serial doppler echocardiogran were performed three time 7, within 3 days after onset( 1st phase ) ,about 12 days ( 2nd phase ), after 4 weeks ( 3rd phase). 1. Concerning left. ventricular diastolic function, A/E in anterior infarct group(1.04± 0.18) nod inferior inifarct group(1.07±0.23) was granter than in that of contol group(0.64±0.10)(P〈O.05), Corrected isovolumic relaxation tine in anterier infarct group (2.34± 0. 60√MS) and inferior infarct group (2.43±0.70√MS) was 1onger than in that of control(1.83±0.31√MS)(P<0.05), 0.33 area fraction ant E ares fraction in anterior infarct group(45± 7%, 55 ±5%, respectively and inferior infarct group ( 43±9%, 53±8%, respectively )were lesser than in thosee of control group(59±9%, 67±5%,respectively) (P<0.05, p<0.05, respectively) , and A area fraction in anterior infarct group ( 43±6%) end inferior infarct 970up(47±8%) was greater group(36±7%) (P<0.05). 2. In the right ventricular sided group (0.86±0.23) and inferior infarct group (1.01±0.16) was greater 7han in that of contol group (0. 62± 0.10) (P<0.05), peak A velucity in inferier infarct group (0.44±0.09 m/s) was higher than in those of anterior infarct group ( 0.36±0.10m/s) and control(0.28±0.05 m/s)(P<0.05) , 0.33 area fraction and E area fraction in anterior infarct group (43 ±7%, 52±10%, respectively) rand inferior infarct group (42± 9%, 50±10%,repectively) were lessser than in those of control group(56±9%,63±7%)(P<0.05, p<0.05, respectively), and A area fraction in anterior infarct group ( 48±10%) and inferior infarct group(49±9%) was greater than in that of control group(36±7%)(P<0.05). 3. Serial left ventricular pulsed doppler echocardiogram in 12 patients with acute myocardial infarction showed following results. A/E in phase 2(0.86±0.17) and phase 3(0.83±0.21) was lesser than in that of phase 1 (1.07±0.22)(P〈O.05), 0.33 area fraction and E area fraction in chase 2( 53±10%, 59±8%,rwspectively) and phase 3( 55±9%, 59±7%, respectively) were greater than in those of phase 1 (43±8%, 49±9%,respectively) (P<0.05, p<0.05, respectively) , A area fraction in phase 3 ( 39±8%) and chase 3( 39±8%) was lesser than in phase 1 (49±11%)(P<0.05), and these variables were net changed between phase 2 and phase 3. 4. Serial right ventricular pulsed doppler echooardiogram in 12 patients with acute myocardial infarction skewed following results, A in phase 2 (0.35±0.10 m/s) and please 3 (0.31±0.06ms) was low than in that of phase 1 (0.46±0.09m/s)(P<0.05), A/E in phase 2(0.92±0.26) and phase 3(0.78± 0.18) was lesser than in that of phase 1(1.10±0.16)(P〈0.05, P〈0.01, respectively), 0.33 area fraction and E area fraction in phase 2( 53±10%, 47±9%, respectively)and phase 3 (58± 8%, 42±9%, respectively) were greater than in those of phase 1 (41±10%, 49±8%, respectively)(P<0.05, P<0.05, respectively), and A area fraction in phase 2 ( 47±9%)and phase 3( 42±9%) was lesser than in that of phase 1(50±7%)(P〈O.05). 5. Left ventricular end0diastolic pressure had a significant high correlation with A/E (r=0.76, P=0.01), with 0.33 area fraction (r=-0.71, P=0.02), and with E area fraction(r=-0.71, P=0.02), in transmitral inflow velocity curve. In conclusion, limition of left and right ventricular early diastolic filling was observed both in patients with anterior and inferior wall infarction. An importment of impaired diastolic ventricular function was after onset of acute myocardial infarction infarction) in patients with acute myocardial infarction. The doppler echocardiographic indices of left ventricuar diastolic function had a significant correlation with left ventricular end-diasolic pressure measured by catheterization.restrictio

Clonal architecture of normal and atherosclerotic aorta: Implications for atherogenesis and vascular development

X chromosome inactivation studies indicate that smooth muscle cells in human atherosclerosis are monoclonal. Monoclonality could arise either by 1) proliferation of a single cell in the adult intima, eg, by selection or mutation, or 2) proliferation of many cells within a large, pre-existing clonal patch that formed during development. To determine whether clonal expansion occurs concomitantly with plaque growth or as part of normal development, X chromosome inactivation patterns were mapped in microdissected samples of aortic smooth muscle, using the human androgen receptor locus as a marker. As expected, 43% of plaque samples were skewed toward one X chromosome, indicating a monoclonal population. Surprisingly, 25% of normal medial samples and 31% of diffuse intimal thickening samples also were skewed toward one X chromosome, indicating a relatively large patch size. Furthermore, 30% of diffuse intimal thickening and 22% of medial samples showed contiguous regions of 4 mm skewed to the same allele, showing that patch length often exceeded 4 min. Intima and overlying media typically were skewed to the same allele (73% concordance), suggesting common cells of origin. Because patch size is large in normal arteries, X-inactivation analysis cannot discriminate between a monoclonal and a polyclonal origin of plaque smooth muscle cells. We propose that human arteries grow by expanding coherent smooth muscle clones, with little mixing of adjacent clones. Determining whether plaques arise by clonal expansion will require other approaches, such as analysis of somatic mutations; the finding of large X- inactivation patches raises the possibility that plaques arise from a pre- existing (developmental) clone

Overexpression of transforming growth factor-β1 in the valvular fibrosis of chronic rheumatic heart disease

For the purpose of determining the pathogenic role of transforming growth factor-β1 (TGF-β1) in the mechanism of chronic rheumatic heart disease, we evaluated the expression of TGF-β1, proliferation of myofibroblasts, and changes in extracellular matrix components including collagen and proteoglycan in 30 rheumatic mitral valves and in 15 control valves. High TGF-β1 expression was identified in 21 cases (70%) of rheumatic mitral valves, whereas only 3 cases (20%) of the control group showed high TGF-β1 expression (p&amp;amp;lt;0.001). Additionally, increased proliferation of myofibroblasts was observed in the rheumatic valves. High TGF-β1 expression positively correlated with the proliferation of myofibroblasts (p=0.004), valvular fibrosis (p&amp;amp;lt; 0.001), inflammatory cell infiltration (p=0.004), neovascularization (p=0.007), and calcification (p&amp;amp;lt;0.001) in the valvular leaflets. The ratio of proteoglycan to collagen deposition inversely correlated with TGF-β1 expression in mitral valves (p=0.040). In conclusion, an ongoing inflammatory process, the expression of TGF-β1, and proliferation of myofibroblasts within the valves have a potential role in the valvular fibrosis, calcification, and changes in the extracellular matrix that lead to the scarring sequelae of rheumatic heart disease. Copyright © The Korean Academy of Medical Sciences

Erratum: Catheter-based adenovirus-mediated local intravascular gene delivery of a soluble TGF-β type II receptor using an infiltrator in porcine coronary arteries: Efficacy and complications (Experimental and Molecular Medicine (2002) 34 (299-307))

[No abstract available

Blockade of TGF-β by catheter-based local intravascular gene delivery does not alter the in-stent neointimal response, but enhances inflammation in pig coronary arteries

Background: Extracellular matrix (ECM) accumulation significantly contributes to in-stent restenosis. In this regard, transforming growth factor (TGF)-β, a positive regulator of ECM deposition, may be implicated in in-stent restenosis. The goal of this study was to assess the effect of blockade of TGF-β on stent-induced restenosis in porcine coronary arteries. Methods: An adenovirus expressing the ectodomain of the TGF-β type II receptor (AdTβ-ExR) was applied onto a coronary arterial segment of a pig (n = 10) using an Infiltrator TM, followed by stent deployment. Controls consisted of adenoviruses expressing β-galactosidase (AdLacZ) or phosphate-buffered saline (PBS) applied onto the other segment (n = 10) of the same pig. Results: Computer-based pathological morphometric analysis of stented coronary arteries, performed 4 weeks after stenting, demonstrated no significant difference in morphometric parameters such as in-stent neointimal area and % area stenosis between the AdTβ-ExR group and control (n = 7 for each). However the AdTβ-ExR group had increased neointimal cell density, infiltration of inflammatory cells mostly consisting of CD3 + T cell, accumulation of hyaluronan, cell proliferation rate, and adventitial matrix metalloproteinase-1 (MMP-1) expression compared with control. The expression of connective tissue growth factor mRNA, measured by reverse transcription PCR, in cultured rat arterial smooth muscle cells was inhibited by AdTβ-ExR at moi 60. Conclusions: Blockade of TGF-β by catheter-based local intravascular gene delivery does not reduce stent-induced neointima formation 4 weeks after stenting in spite of modest inhibition of ECM accumulation, but it induces vascular inflammation and associated pathological changes that may potentially aggravate lesion progression. © 2009 Elsevier Ireland Ltd