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1 대한류마티스학회지 Vol. 16, No. 3, September, 2009 DOI: /jkra 원저 폐경기이후의섬유근통환자에서심장기능의평가 메리놀병원류마티스내과 1, 순환기내과 2 강지현 1 ㆍ이지현 1 ㆍ조경임 2 ㆍ김태익 2 ㆍ권혁용 1 ㆍ김현진 1 ㆍ김명준 1 ㆍ황치성 1 =Abstract= Assessing the Myocardial Function of Postmenopausal Women with Fibromyalgia Ji-Hyun Kang 1, Ji-Hyun Lee 1, Kyoung-Im Cho 2, Tae-Ik Kim 2, Hyuk-Yong Kwon 1, Hyeon-Jin Kim 1, Myoung-Joon Kim 1, Chi-Sung Hwang 1 Divisions of Rheumatolgy 1 and Cardiology 2, Department of Internal Medicine, Maryknoll Hospital, Buasn, Korea Background: Aberrations of cardiovascular regulation have been reported in patients who suffer with fibromyalgia (FM). Abnormalities of the cardiovascular autonomic regulation, as well as the correlation between coronary heart disease and depression, have been considered to be the causative factors. The clinical features of transient left apical ballooning syndrome with the patients under acute stress have been clearly described, but the effect of chronic stress such as FM on the myocardium is unknown. We investigated the cardiac strain in FM patients by strain imaging with using the 2D grayscale images, and we quantified the regional myocardial deformation properties. Methods: We investigated 30 consecutive postmenopausal women (mean age: 48±8 years) who satisfied the criteria for fibromyalgia with atypical chest pain by performing standard and 2-dimensional strain echocardiography (2DS). Those patients with hypertension, coronary heart disease or diabetes were excluded. The global and segmental longitudinal deformation parameters of the LV from 3 apical views were analyzed, and the patients underwent a manual tender point survey for determining the number of tender points and tender point counts, and the patients completed the fibromyalgia impact questionnaire (FIQ), the brief fatigue inventory (BFI), and Beck depression inventory (BDI). Results: The global longitudinal LV strain was significantly reduced in the FM patients with <접수일 :2009년 6월 2일, 수정일 :2009년 7월 10일, 심사통과일 :2009년 7월 16일> 통신저자 : 이지현부산시중구대청동 4가 12번지메리놀병원류마티스내과 Tel:051) , Fax:051) , ete@lycos.co.kr 189

2 대한류마티스학회지제 16 권제 3 호 2009 a high FIQ score (>40) as compared to the patients with a low FIQ score ( 18.61% vs %). Also, both the global and segmental longitudinal LV strains were negatively associated with fatigue or the tender point counts. However, there was no significant association between depression and the LV strain. Conclusion: This study showed the reduced myocardial longitudinal deformation in FM patients. This suggested that strain imaging is a feasible approach to assess the regional ventricular function in FM patients. Key Words: Fibromyalgia, Stress, Echocardiography, Strain 서 론 대상및방법 섬유근통증후군은주위에서흔히접할수있는만성적인근골격계질환으로광범위한근골격계의통증과강직및특정부위의압통, 이상감각, 수면장애, 잦은피로감을특징으로하는질환이다 (1,2). 이질환의원인은아직명확히밝혀지지는않았으나현재신체적외상, 감염질환, 정신적인스트레스, 유전적요인으로생각되어진다 (3). 섬유근통환자들에서심혈관조절에이상이있는것은이미몇몇연구에서보고되어져왔다 (4,5). 우울증에서관찰되어지는심혈관질환과마찬가지로섬유근통에서도심혈관기관의자동조절능력의이상이심혈관질환의원인의일부로생각되어지고있다 (6,7). 만성적인스트레스시지속적인교감신경의항진과시상하부-뇌하수체-부신축 (HPA axis) 의활성화를통해심혈관의내피세포에부정적인영향을주는것으로알려져있으며 (8) 심한스트레스상황에서는심첨풍선증후군 (apical ballooning syndrome) 과같은심질환도발병하는것으로보고되고있다 (9-11). 또한섬유근통환자에서압통점의개수및 Fiboromyalgia Impact Questionnaire (FIQ) 점수가관상동맥조영술시관찰되는병적인소견과관련이있다는보고도있다 (12). 본연구에서는섬유근통환자를대상으로새로운초음파방법인이면성그레이스케일영상 (2-dimension grayscale image) 을이용, 심장변형 (cardiac strain) 값을구하여심장기능을조사하고환자들의임상적특징을분석하여섬유근통의정도와심장기능사이의연관성을조사하였다. 1. 연구대상대상환자군은 2008년 9월에서 2009년 3월까지본원류마티스내과와순환기내과를방문한환자중비전형적인흉통을호소하는폐경기이후의섬유근통환자 30명을대상으로하였다. 심초음파검사는신체검사및병력청취, 설문지조사후에시행하였으며허혈성심질환을배제하기위해운동부하검사를시행하였다. 대조군은동일연령의건강한여성 20명을대상으로하였으며정상적인심초음파검사소견및운동부하검사결과를가지는사람들을포함시켰다. 대상환자중고혈압, 심혈관질환, 당뇨, 뚜렷한판막질환자및진행된부정맥을가진환자들은이조사에서제외시켰다. 2. 연구방법위환자들을대상으로, 내과전공의가 1:1 면담을통해연구목적의취지및방법등을설명하고동의서를받은후에신체검사및병력청취, 사회인구학적인특성, 건강관련삶의질, 질환특이건강상태, 삶의질에영향을미치는기타요소등을다음과같은방법으로조사하였으며이들에대한심장기능의평가는새로운초음파방법인표준이면성변형심초음파검사 (2-dimensional strain echocardiography (2DS)) 를이용하여심장변형값을구하였다. 1) 신체검사및병력청취섬유근통을진단하기위해 1990년개정된미국류마티스학회 (ACR) 의진단기준을사용하였다 (1). 2) 질환별임상특성-통점 (Tender point) 한명의류마티스내과전문의가모든환자들을대 190

3 강지현외 : 섬유근통환자에서심장기능의평가 상으로엄지손가락을이용하여통점을측정하였으며오른쪽, 왼쪽각각 18군데의압점에대한통각을정도에따라 0점에서 3점까지로구분하여통점값 (tender point count) 을구하였다. 3) 사회인구학적특성 (Sociodemographic feature) 이번연구에참석한환자군을대상으로이름, 성별, 키, 몸무게, 생년월일, 교육정도, 결혼유무, 최종학력, 의료보험가입상태, 동반질환유무를설문을통하여조사하였다. 4) 질환특이건강상태측정도구 (Korean Fibromyagia Implact Questionnaire (KFIQ)) FIQ는 1991년 Bennett 등에의해개발된도구로 (13), 본연구에서는교차-문화적적응작업과확인과정을시행한한국어판 KFIQ (14) 를사용하였다. KFIQ는신체적능력, 기분, 업무능력, 통증, 피로, 휴식, 강직, 우울, 불안등에관한 20개의문항으로구성되어있으며, 각증상의정도를기록하도록되어있다. 우선 1번부터 11번까지의문항은일상생활의수행정도를평가하는것으로항상할수있다, 대부분할수있다, 가끔할수있다, 절대못한다의네가지로구분하여응답하도록하였으며 12번문항은환자의기분을평가하는것으로지난일주일간기분좋았던날수를기록하도록하였으며 13번문항은섬유근통으로인한일 ( 집안일혹은직장일 ) 이불가능한날수를기록하도록하였다. 14번부터 20번까지의문항은통증, 피곤함, 강직, 불안, 우울등의항목에대해지난주에경험하였던각증상의정도를 0 에서 10까지나누어가장심한정도를 10으로하여응답하도록하였다. 우리는이값에기초하여섬유근통환자를높은 FIQ값을가지는군 A (FIQ 40) 와낮은 FIQ값을가지는군 B (FIQ<40) 로각각나누어조사하였다. 5) 건강관련삶의질측정도구-Brief fatigue inventory Brief Fatigue Inventory (BFI) 는원래암환자에서피로도 (fatigue) 와이와관련된장애의정도를측정하여그들의삶의질을평가하기위해고안된설문지 (15) 로총 9가지의질문으로구성되어있으며각각의문항은 0 10점으로평가된다. 피로도의정도는크게경함 (mild), 보통 (moderate), 심함 (severe) 으로구분하며각각 1 3점, 4 6점, 7 10점으로나누어진다. 6) 심리사회적인자-Brief depression inventory 전세계적으로널리사용되고있는 Brief Dpression Inventory (BDI) 는우울증상의유무와그심각성을측정하기위해고안된개개문항의자기보고식질문지 (16) 로우울증의인지적, 정서적, 동기적, 신체적증상영역을포함하는 21가지의문항으로 21 개문항에대해각각 0 3점으로평가되며전체점수는 0 63점으로점수가높을수록우울증이심한것을나타낸다. 7) 심초음파검사표준이면성변형심초음파검사는 Vivid 7 dimension ultrasound (General Electric, Horten, Norway) 의 3.5-MHz 탐촉자 (transducer) 를이용하여환자의좌측와위 (left lateral supine position) 에서시행하였다. 이면성심초음파영상 (frame rate 70s) 과조직도플러영상 (color Doppler tissue imaging (frame rate 115s)) 은좁은각 (narrow sector angle) 을이용하여 2방도 (2 chamber view), 3방도 (3 chamber view), 4방도 (4 chamber view) 의검사를시행하였다 ( 그림 1). 좌심실의심첨방도 (apical chamber view image) 는환자에게끝까지숨을내쉬고참게한후에얻은것이고그후에 offline 분석을통해 cineloop format에저장하였다. 각시야 (view) 로부터얻은세가지심장박동 (three heartbeat) 은 EchoPAC Dimension system (General Electric, Horten, Norway) 으로분석하였고심근의장축에대한국소적인기능 (Longitudinal myocardial regional function) 을평가하기위해최대수축변형 (Peak systolic strains) 을측정하고평균값을구하였다. 전반적인좌심실변형 (Global LV strain, GLS) 값은심첨 4방도 (apical 4 chamber view), 2방도및장축단면도 (long asix view) 의각각의국소변형값 (segmental value) 의평균을통해구하였다. 3. 통계분석모든측정결과는중간값 (median), 사분위수범위 (interquartile range), 퍼센트등으로제시하였다. 측정결과들은 standard statistical software (SPSS package version 11.0, Chicago, IL) 을이용하여평가하였으며모든측정값들의비교는 Mann-Whitney U test를통하여분석하였다. 상관관계값을구하기위해서 Spearman correlation coefficient를이용하였으며 p값은

대한류마티스학회지 제 16 권 제 3 호 2009 Fig. 1. Longitudinal strain was obtained from the 3 apical chamber views by 2-dimensional speckle tracking strain analysis.

대상 환자의 사회 인구학적, 임상적 특성 섬유근육통 환자의 평균 연령은 48±8세(42 66세) BMI (kg/m2) 였으며 전반적인 좌심실 수축력, 좌심실 방 차원(LV chamber dimension)과 벽 두께는 모든 섬유근통 환자 에서 정상이었다.

임상적 특징을 살펴보면 신 체 점수(physical score), 통점의 수(number of tender point) 등은 두 그룹간에 유의한 차이를 보이지 않았 다.

HR (bpm) Disease duration after diagnosis (years) Group A Group B (n=20) (n=10) Control (n=20) 46 (9.75) 23.18 (3.6275) 125.5 (15.5) 79.5 (10.25) 72 (6.

4 대한류마티스학회지 제 16 권 제 3 호 2009 Fig. 1. Longitudinal strain was obtained from the 3 apical chamber views by 2-dimensional speckle tracking strain analysis. 미만인 것을 통계적으로 유의한 것으로 판정하였다. 결 Table 1. Baseline demographic characteristics of the FMS patients and the controls 과 Age (years) 1. 대상 환자의 사회 인구학적, 임상적 특성 섬유근육통 환자의 평균 연령은 48±8세(42 66세) BMI (kg/m2) 였으며 전반적인 좌심실 수축력, 좌심실 방 차원(LV chamber dimension)과 벽 두께는 모든 섬유근통 환자 에서 정상이었다. 전반적인 대상자들의 사회인구학 Systolic BP (mmhg) Diastolic BP (mmhg) 적 특성은 표 1과 같다. 임상적 특징을 살펴보면 신 체 점수(physical score), 통점의 수(number of tender point) 등은 두 그룹간에 유의한 차이를 보이지 않았 다. 그러나 신체 점수, 기분 점수(peel score), 통점값, 피로도(BFI) 및 일을 하지 못한 날(work miss) 값은 높은 FIQ값을 가지는 군에서 낮은 FIQ값을 가지는 군과 비교하여 높게 나타났으며 이중 일을 하지 못 한 날과 피로도는 높은 FIQ값을 가지는 군에서 월 HR (bpm) Disease duration after diagnosis (years) Group A Group B (n=20) (n=10) Control (n=20) 46 (9.75) (3.6275) (15.5) 79.5 (10.25) 72 (6.6) 11 (9.25) 48 (11.25) (3.125) 125 (15.25) 78.5 (12.75) 74 (14.5) 0 50 (10.5) (1.95) (10.25) 80 (15) 74 (5.325) 5 (4.75) All the values are described as medians (interquartile range), Group A: (FIQ 40), Group B: (FIQ 40), FMS: fibromyalgia syndrome, FIQ: fibromyalgia impact questionnaire, BMI: body mass index, BP: blood pressure, HR: heart rate 192

5 강지현외 : 섬유근통환자에서심장기능의평가 등히높게나타났다 ( 표 2). 2. 변형심장초음파소견 (Strain echocardiographic finding) 심근수행정도 (Myocardial perfomance state) 와승모판유입지표 (mitral inflow parameters) 에서는두그룹간에유의한차이가없었다 ( 표 3). 그러나전반적인 Table 2. Comparisons of the clinical variables between the FMS patients Group A Group B (n=20) (n=10) FIQ (10.11) (5.645) Physical impairment subscale (12.75) (3.5) Feel good subscale (2.86)* (1.43) Work missed subscale (15.5)* (3.5) Number of tender point (2) (3.5) Tender point counts (7.75)* (5.5) Fatigue subscale (BFI) (17.5)* (17.5) Depression subscale (BDI) (13.75)* (6.25) All the values are described as median (interquartile range), Group A: (FIQ 40), Group B: (FIQ<40), FMS: fibromyalgia syndrome, FIQ: fibromyalgia impact questionnaire, *p<0.05 vs. group B p 좌심실변형 (global LV strain, GLS) 은높은 FIQ값을가지는 A군 (FIQ 40) 에서낮은 FIQ값을가지는 B군 (FIQ<40) 과비교하여 ( 18.8 VS 23.2) 뚜렷하게감소하였으며특히심첨장축도 (apical long asix view) 에서의더낮은수축변형 (systolic strain) 값 ( VS 23.5) 을가졌다 ( 표 4). FIQ는전반적인좌심실변형과국소적인좌심실변형 (segmental LV strain, SLS) 모두강한상관관계가있는것으로나타났으며그중일상생활에서의수행정도, 기분과 GLS값과는뚜렷한상관관계가증명되었으며그들의 Spearman의상관계수는각각 r=0.47, 0.57, p<0.05으로통계적으로의미있는상관관계를보였다. GLS의값은 FIQ 의모든문항과강한상관관계를가지고있었으며 Table 3. Parameters of the 2-dimensional echocardiography between the FMS patients and the controls Group A Group B Control (n=20) (n=10) (n=20) LVEDd (mm) (4.875) 44.2 (1.85) (3.125) FS 35.5 (4) 35 (1.75) 34.5 (3.5) EF (%) 65 (5) 65 (1.75) 67 (3) RWT 0.42 (0.065) 0.42 (0.035) 0.41 (0.04) LVMI (g/m 2 ) 97.5 (23.75) 90 (11.5) 92.5 (15.25) LAD (mm) 37.8 (2.9) 34.8 (0.9) 36.8 (1.8) All the values are described as medians (interquartile range), Group A: (FIQ 40), Group B: (FIQ<40), FMS: fibromyalgia syndrome, LVEDd: left ventricular end diastolic dimension, FS: fractional shortening, EF: ejection fraction, RWT: relative wall thickness, LVMI: left ventricular mass index, LAD: left atrial dimension, *p<0.05 vs. group B, **p<0.05 vs. control Table 4. Parameters of the mitral inflow pattern and strain between the FMS patients Group A (n=20) Group B (n=10) Control (n=20) E velocity (cm/sec) 75 (20) 72 (19.5) 74 (14.5) A velocity (cm/sec) 68.5 (10.75) 68 (9.75) 68 (12.5) E/Ea 8.15 (1.97) 8.66 (1.365) 8.05 (2.13) Peak systolic strain, LAX (%) (4.2)*,** 23.5 (2.975) 22.5 (3.125) Peak systolic strain, A4C (%) 19 (2.925)*,** 23.2 (1.575) 23.5 (1.225) Peak early diastoic strain, A2C (%) (3.6)*,** 23 (1.375) 24 (2.8) Global LV strain (%) 18.8 (3.45)*,** 23.2 (2.125) 23.5 (1.875) All the values are described as medians (interquartile range), Group A: (FIQ 40), Group B: (FIQ<40): FMS: fibromyalgia syndrome, E: peak early velocity, A: peak atrial velocity, Ea: early diastolic mitral annular velocity, LAX: apical long axis view, A4C: apical 4-chamber view, A2C: apical 2-chamber view, *p<0.05 vs. group B, **p<0.05 vs. control 193

6 대한류마티스학회지제 16 권제 3 호 2009 Table 5. Correlation analysis of the parameters between the patients with FMS; Spearman s correlation coefficient (r) Global LV strain of patients with FMS r p FIQ score ** Physical score * Feel score ** Work miss * Number of tender point Depression (BDI) Fatigue (BFI) * E/Ea FMS: fibromyalgia syndrome, BDI: beck depression inventory, BFI: brief fatigue inventory, FIQ: fibromyalgia impact questionnaire, E: peak early velocity, Ea: early diastolic mitral annular velocity, *p<0.05, **p<0.01 그중에서도통점값, 일을하지못한날, 피로도와각각 r=0.45, 0.40, 0.46로의미있는관계를가졌다 ( 표 5). 그러나 BDI와통점의수는유의한상관관계가없었다. 고 섬유근통은광범위한통증및통각과민 (hyperalgesia), 무해자극통증 (allodynia) 으로특징지어지는질환으로섬유근통환자는잦은피로, 수면장애, 두통, 불안등을경험한다 (1,2). 섬유근통에대한원인은여러가지가설들이분분하나아직명확히밝혀진것이없다. 다양한형태의신체적외상 (17), 감염성질환 (18), 정신적인충격, 그리고유전적소인 (19) 이연관성이있는것으로생각되고그중신체적혹은정신적스트레스가밀접한관계가있는것으로생각된다. 이러한스트레스가심혈관질환과연관성이있다는것은이미알려진사실이며만성적인스트레스상황, 예를들어과중한업무, 결혼에대한스트레스, 낮은사회적지위, 낮은소득, 만성질환등이심혈관질환및심장에대한나쁜영향을미칠수있는위험요소를증가시킨다는것도이미알려진사실이다 (20,21). 우리는이번연구에서이면성심초음파기계를이용하여섬유근통에서심장기능의이상유무를조사하고환자들의임상적특징을분석 찰 하여섬유근통과심장기능과의연관성에관해조사하였다. 변형 (strain) 과변형률 (strain rate) 이란가해진힘에비례한조직의상대적인변화의양과속도를뜻하는것으로 (22), 심근에서의변형은가해진힘에대한심근조직의상대적변형으로이완기말상태 (L 0) 에대한수축기말상태로변형된정도 (ΔL) 를나타내며단위는없거나 % 로표시된다 (23). 이러한변형은공간적으로방사변형 (radial strain), 장축변형 (longitudinal strain), 원주변형 (circumferential strain) 으로구분되며음의값을가지는것은심근이짧아지거나, 얇아지거나, 눌리는것 (shortening, thinning, compression) 을의미한다 (24). 최근연구에서는최고변형 (peak strain) 값은좌심실의박출률 (LVEF) 과관련이있고변형률은심실의수축력과연관성이있으며, 정상인의심장한부위의변형및변형률은전체좌심실의수축기기능을반영한다고보고하고있다 (25,26). 본연구에서전반적인좌심실변형값 (GLS) 은높은 FIQ 값을가지는그룹이낮은 FIQ값을가지는그룹을비교하였을때적은수축변형값을가졌으며그외에도전반적및국소적인좌심실변형둘다가피로, 통점값과음의상관관계가있는것으로나타났다. 그러나우울정도와심장변형사이에는별다른연관성을보이지않았다. 본연구에서는섬유근통환자에서 FIQ score, 피로도, 통점값에따라장축변형 (longitudinal deformation) 이변화되는것을보여주었고이는교감신경계의항진으로인한미세순환장애 (microcirculatory impairment) 혹은내피세포기능장애에의해생기는것으로생각되어진다 (27,28). 본연구의제한점으로, 우선낮은 FIQ값을가진그룹에서대조군과비교하여변형값에있어별다른차이가없었다는것으로이는좌심실기능에충분히영향을미칠만큼스트레스가심하지않았거나혹은낮은 FIQ값을가지는군의환자들이스트레스에민감하지않은것으로생각되어진다. 그러나높은 FIQ 값을가지는섬유근통환자군에서좌심실기능이상대적으로감소된것은스트레스그자체로인한것인지아니면질병의특성인지는명확하지않다. 두번째로본연구는단면조사연구로참가한환자의수가적었으며앞으로대규모의전향적인연구가필요할것으로생각된다. 194

7 강지현외 : 섬유근통환자에서심장기능의평가 이번연구에서우리는섬유근통환자에서그정도에따라심장의기능에부정적인영향을미친다는것을알수있었고이는섬유근통이만성적인스트레스로작용하여교감신경계의항진으로인한심근의손상을가져올것이라고생각된다. 참고문헌 1)Wolfe F, Smythe HA, Yunus MB, Bennett RM, Bombardier C, Goldenberg DL, et al. The American College of Rheumatology 1990 Criteria for the Classification of Fibromyalgia. Report of the Multicenter Criteria Committee. Arthritis Rheum 1990;33: ) Pongratx DE, Sievers M. Fibromyalgia-symptom or diagnosis: a definition of the position. Scans J Rheumatol Suppl 2000;113:3-7. 3) Bradely LA. Pathophysiologic mechanisms of fibromyalgia and its related disoders. J clin psychiatry 2008;69 Suppl 2: ) Furlan R, Colombo S, Perego F, Atzeni F, Diana A, Barbic F, et al. Abnormalities of cardiovascular neural control and reduced orthostatic tolerance in patients with primary fibromyalgia. J Rheumatol 2005;32: ) Naschitz JE, Rozenbaum M, Rosner I, Sabo E, Priselac RM, Shaviv N, et al. Cardiovascular response to upright tilt in fibromyalgia differs from that in chronic fatigue syndrome. J Rheumatol 2001;28: ) Naschitz JE, Rozenbaum M, Fields MC, Enis S, Manor H, Dreyfuss D, et al. Cardiovascular reactivity in fibromyalgia: evidence for pathogenic heterogeneity. J Rheumatol 2005;32: ) Patten SB, Beck CA, Kassam A, Williams JV, Barbui C, Metz LM. Long-term medical conditions and major depression: strength of association for specific conditions in the general population. Can J Psychiatry 2005;50: ) McEwen BS. Protective and damaging effects of stress mediators: central role of the brain. Dialogues Clin Neurosci 2006;8: ) Wittstein IS. Acute stress cardiomyopathy. Curr Heart Fail Rep 2008;5: )Pavin D, Le Breton H, Daubert C. Human stress cardiomyopathy mimicking acute myocardial syndrome. Heart 1997;78: ) Prasad A, Lerman A, Rihal CS. Apical ballooning syndrome (Tako-Tsubo or stress cardiomyopathy): a mimic of acute myocardial infarction. Am Heart J 2008;155: ) Ablin JN, Beilinson N, Aloush V, Elkayam O, Finkelstein A. Association between fibromylagia and coronary heart disease and coronary catheterization. Clin Cardiol 2009;32: ) Burckhardt CS, clark SR, Bennett RM. The fibromyalgia impact questionnaire: development and validation. J Rheumatol 1991;18: ) Kim YA, Lee SS, Park K. Validation of a Korean version of the fibromyagia impact questionnaire. J Korean Med Sci 2002;17: ) Mendoza TR, Wang XS, Cleeland CS, Morrissey M, Johnson BA, Wendt JK, et al. The rapid assessment of fatigue severity in cancer patients: use of the brief fatigue inventory. Cancer 1999;85: ) Richter P, Werner J, Heerlein A, Kraus A, Sauer H. On the validity of the beck depression inventory. Psychopathology 1998;31: ) Buskila D, Neumann L, Vaisberg G, Alkalay D, Wolfe F. Increased rates of fibromyalgia following cervical spine injury. A controlled study of 161 cases of traumatic injury. Arthritis Rheum 1997;40: ) Adak B, Tekeoğlu I, Ediz L, Budancamanak M, Yazgan T, Karahocagil K, et al. Fibromyalgia frequency in hepatitis B carriers. A. J Clin Rheumatol 2005;11: ) Ablin JN, Cohen H, Buskila D. Mechanisms of disease: genetics of fibromyalgia. Nat Clin Pract Rheumatol 2006;2: ) Blumenthal JA, Babyak MA, Moore KA, Craighead WE, Herman S, Khatri P, et al. Effects of exercise training on older patients with major depression. Arch Intern Med 1999;159: ) Rozanski A, Blumenthal JA, Davidson KW, Saab PG, Kubzansky L. The epidemiology, pathophysiology, and management of psychosocial risk factors in cardiac practice: the emerging field of behavioral cardiology. J Am Coll Cardiol 2005;45: ) Pislaru C, Abraham TP, Belohlavek M. Strain and strain rate echocardiography. Curr Opin Cardiol 2002; 17: ) Gilman G, Khandheria BK, Hagen ME, Abraham TP, Seward JB, Belohlavek M. Strain rate and strain: a step-by-step approach to image and data acquisition. J Am Soc Echocardiogr 2004;17: ) D'hooge J, Heimdal A, Jamal F, Kukulski T, Bijnens B, Rademakers F, et al. Regional strain and strain rate 195

8 대한류마티스학회지제 16 권제 3 호 2009 measurements by cardiac ultrasound: principles, implementation and limitations. Eur J Echocardiogr 2000;1: ) Pislaru C, Abraham TP, Belohavek M. Strain and strain rate echocardiography. Curr Opin Cardiol 2002; 17: ) Lee YA, Lee BH, Kang HS, Park JY, Choue CW, Song JS, et al. The change of tissue velocity and strain rate after exercise in patients with coronary artery disease. Korean Circ J 2003;33: ) Ghiadoni L, Donald AE, Cropley M, Mullen MJ, Oakley G, Taylor M, et al. Mental stress induces transient endothelial dysfunction in humans. Circulation 2000;102: ) Rozanski A, Blumenthal JA, Kaplan J. Impact of psychological factors on the pathogenesis of cardiovascular disease and implications for therapy. Circulation 1999;99:

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<4D F736F F F696E74202D20BFA1C4DA5FC0D3BBF3C3CAC0BDC6C42E BC8A3C8AF20B8F0B5E55D> 심장 (Heart) 심초음파 서울대병원내과 김용진 심장은평생몇번이나뛸까요? 1) 3 백만번 2) 3 천만번 3) 3 억번 4) 30 억번 30 억박동, 2 억리터의혈액 Cause 심장질환 6.2 12.4 11.1 16.2 뇌졸중 4.3 8.5 7.7 11.3 기타심혈관질환 2.6 5.1 6.0 8.8 심혈관질환 13.1 26.0 24.8 36.3 총사망 50.4