지 선 하 연세대학교 보건대학원 서울시 대사증후군 연구사업단 제 15회 대한고혈압학회 춘계 학술대회, 2006. 5. 27 140/90 더 낮춰야 한다 지 선 하 연세대학교 보건대학원 서울시 대사증후군 연구사업단

“Prehypertension” 45 million Americans Systolic BP: 120-139 mm Hg OR Diastolic BP: 80-89 mm Hg JNC VI Report JAMA, 2003

CVD mortality risk doubles with each 20/10 mm Hg BP increment* 8 7 6 CV mortality risk 5 4 3 2 1 Slide Summary According to a meta-analysis of over 60 prospective studies, the risk of cardiovascular mortality doubles with each rise of 20 mm Hg in systolic blood pressure (BP) and 10 mm Hg in diastolic BP. Background In a meta-analysis of 61 prospective, observational studies conducted by Lewington et al involving one million adults with no previous vascular disease at baseline, the researchers found that between the ages of 40-69 years, each incremental rise of 20 mm Hg systolic BP and 10 mm Hg diastolic BP was associated with a twofold increase in death rates from ischemic heart disease and other vascular disease. The researchers also noted that when attempting to predict vascular mortality risk from a single BP measurement, the average of systolic and diastolic BP was “slightly more informative” than either alone, and that pulse pressure was “much less informative.” The seventh report Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) notes this study result as yet more information linking hypertension to high risk for cardiovascular events. Lewington S, Clarke R, Qizilbash H, et al. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet. 2003;361:1903-1913. JNC 7. JAMA. 2003;289:2560-2572. 115/75 135/85 155/95 175/105 Blood Pressure (mm Hg) *Individuals aged 40-70 years, starting at BP 115/75 mm Hg. Lewington S, et al. Lancet. 2002 JNC VII JAMA 2003

Impact of high-normal BP on CVD risk 16 16 14 14 Men Men High-normal BP 12 12 Cumulative incidence of CV events (%) 10 10 Normal BP 8 8 6 6 Optimal BP 4 4 2 2 12 12 Cumulative incidence of CV events (%) 10 10 Women Women High-normal BP 8 8 6 6 4 Normal BP High-normal blood pressure (BP) is associated with an increased risk for cardiovascular disease (CVD). The association between baseline BP and the incidence of CVD on follow-up was investigated in 6859 participants in the Framingham Heart Study who were initially free of hypertension and CVD [Vassan et al, 2001]. A stepwise increase in cardiovascular (CV) event rates was noted in subjects with higher baseline BP levels. The 10-year cumulative incidence of CVD in subjects aged 35 to 64 years with high-normal BP at baseline (systolic BP: 130-139 mm Hg; diastolic BP: 85-89 mm Hg) was 4% in women and 8% in men. In older subjects (aged 65 to 90 years), the CV incidence was 18% in women and 25% in men. Compared with optimal BP, high-normal BP was associated with a risk factor–adjusted hazards ratio of 2.5 in women and 1.6 in men. 4 2 2 Optimal BP 2 2 4 4 6 6 8 8 10 10 12 12 Years Years Optimal BP: <120/80 mm Hg; normal BP: 120-129/80-84 mm Hg high-normal BP: 130-139/85-89 mm Hg Optimal BP: <120/80 mm Hg; normal BP: 120 Vasan RS et al. N Engl J Med 2001

Baseline BP predicts progression to hypertension 4 year hypertension incidence rates, adjusted for sex, age, BMI, and baseline BP Optimal = <120/80 mm Hg Normal = 120-130/80-85 mm Hg High Normal = 130-139/85-89 mm Hg Vasan RS Lancet 2001

Age distribution of KCPS Men Women Age ≥65 60-64 55-59 50-54 45-49 40-44 35-39 30-34 % 15 10 5 5 10 15 %

Study population characteristics at baseline, KCPS, 1992-1995 Men Women Age, year 45.0 49.4 BMI, kg/m2 23.2 SBP, mmHg 124.5 121.5 FBS, mg/dl 92.1 89.9 Total cholesterol, mg/dl 191.7 194.4 Smoking, % Never 20 94 Former 2 Current 60 4

Distribution of Study Participants by Systolic and Diastolic BP in KCPS Diastolic BP, mmHg Systolic BP, mmHg

Selected Publications from KCPS Smoking and Cancer risk (CCC, 2004) Alcohol D., HBsAg and HCC (JNCI, 2004) Diabetes and Cancer risk (JAMA, 2005) WBC count and ASCVD risk (AJE, 2005)

Atherosclerotic Cardiovascular Disease (ASCVD) The principle outcome variables were morbidity and mortality IHD (ICD-9 410-414) Myocardial infarction (ICD-9 410) Cerebrovascular disease Hemorrhagic stroke (ICD-9 430-432) Thrombotic stroke (ICD-9 433-434) Other stroke (ICD-9 435-437) Other heart disease (426-429), sudden death(798), other vascular disease (440-444)

분석방법 12년 전향적 코호트 분석 Cox proportional hazard models adjusting for age, age2, diabetes, total serum cholesterol, and smoking status. Hypertension Attributable Risk (HAR) =[(p0 + p1(RR1) + p2(RR2)) –1]/ [(p0 + p1(RR1) + p2(RR2)] Estimating the Health Consequences of Hypertension Hypertension Attributable Mortality Estimating Years of Potential Life Lost Estimating the Heath-Related Economic Consequences of Hypertension

Systolic BP and ASCVD Risk in Korean Men RR 비교군을 110-119 로 할 경우 위험도 더 올라갈수 있다. 수축기혈압은 120 이하면 만족.. 즉 100-119 가 적정… 110-119 를 기본으로 한 그림이 필요하다.. Normal Pre hypertension Stage 1 Stage 2 Low Pre HTN H. Normal BP

Fig 1. Systolic BP and ASCVD Risk in Korean Men RR P < 0.0001 NS 비교군을 110-119 로 할 경우 위험도 더 올라갈수 있다. 수축기혈압은 120 이하면 만족.. 즉 100-119 가 적정… 110-119 를 기본으로 한 그림이 필요하다.. Normal Pre hypertension Stage 1 Stage 2 Low Pre HTN H. Normal BP

Fig 2. Systolic BP and ASCVD Risk in Korean Women RR P < 0.0001 NS 비교군을 110-119 로 할 경우 위험도 더 올라갈수 있다. 수축기혈압은 120 이하면 만족.. 즉 100-119 가 적정… 110-119 를 기본으로 한 그림이 필요하다.. Normal Pre hypertension Stage 1 Stage 2 Low Pre HTN H. Normal BP

Fig 3. Diastolic BP and ASCVD Risk in Korean Men RR P < 0.0001 * ** ** <65, 65-74??? Normal Pre hypertension Stage 1 Stage 2 Low Pre HTN H. Normal BP

Fig 4. Diastolic BP and ASCVD Risk in Korean Women RR P < 0.0001 * <65, 65-74??? Normal Pre hypertension Stage 1 Stage 2 Low Pre HTN H. Normal BP

Hypertension (JNC 7) and ASCVD Risk in Korean Men RR Normal 1 Normal 2 Normal 3 Pre hypertension Stage 1 Stage 2 Low Pre HTN H. Normal BP

Hypertension (JNC 7) and ASCVD Risk in Korean Men RR Normal 1 Normal 2 Normal 3 Pre hypertension Stage 1 Stage 2 Low Pre HTN H. Normal BP

Hypertension (JNC 7) and ASCVD Risk in Korean Women RR Normal 1 Normal 2 Normal 3 Pre hypertension Stage 1 Stage 2 Low Pre HTN H. Normal BP

Hypertension (JNC 7) and Total Stroke Risk in Korean Men – 발생<사망 RR 더 낮출 경우 5-10 % 위험도 줄인다. 혈압이 뇌졸중에 주는 위험도는 발생보다는 사망에 더 유의하다 –남자 Normal 1 Normal 2 Normal 3 Pre hypertension Stage 1 Stage 2 Low Pre HTN H. Normal BP

Hypertension (JNC 7) and Total Stroke Risk in Korean Women – 발생<사망 RR 더 낮출 경우 20-30 % 위험도 줄인다. 여성 100-109 충분 70-74 혈압이 뇌졸중에 주는 위험도는 발생보다는 사망에 더 유의하다 –여자 여성의 경우 더욱 낮추어도 문제 없다… Normal 1 Normal 2 Normal 3 Pre hypertension Stage 1 Stage 2 Low Pre HTN H. Normal BP

Hypertension and Total Stroke in Korean Men - 젊은 연령 RR Normal 1 Normal 2 Normal 3 Pre hypertension Stage 1 Stage 2 Low Pre HTN H. Normal BP

Hypertension and Total Stroke in Korean Women - 젊은 연령 RR Normal 1 Normal 2 Normal 3 Pre hypertension Stage 1 Stage 2 Low Pre HTN H. Normal BP

Hypertension and IHD in Korean Men - 젊은 연령 RR Normal 1 Normal 2 Normal 3 Pre hypertension Stage 1 Stage 2 Low Pre HTN H. Normal BP

Hypertension and IHD in Korean Women - 젊은 연령 RR Normal 1 Normal 2 Normal 3 Pre hypertension Stage 1 Stage 2 Low Pre HTN H. Normal BP

Risk of Hypertension varies by Age Substantial interest exists in estimating the future burden of hypertension as today’s younger people with hypertension and adults grow older

Distribution of Study Participants by Systolic and Diastolic BP in KCPS Diastolic BP, mmHg Systolic BP, mmHg

Systolic and Diastolic BP and Total Stroke in Korean Men Diastolic BP, mmHg Systolic BP, mmHg

Systolic and Diastolic BP and Total Stroke in Korean Women Diastolic BP, mmHg Systolic BP, mmHg

Systolic and Diastolic BP and Total Stroke in Korean Men and Women Diastolic BP, mmHg Systolic BP, mmHg

Fig 7. Systolic and Diastolic BP and ASCVD in Korean Men and Women Diastolic BP, mmHg Systolic BP, mmHg

Hypertension Attributable Risk (HAR, %) SBP DBP % Pop. HAR Cumul. Specif. 100-119 70-79 26.0 2.8 120-139 80-89 40.0 16.7 13.2 140-159 90-99 24.4 27.0 10.3 >160 >100 9.6 33.8 6.8 140/90 이하에서 심뇌혈관 질환 발생의 혈압기여도 절반이 된다.. 따라서 110/80 (75) 이하로 낮추는 것이 바람직하다..

Systolic and Diastolic BP and Total Stroke in Korean Men Fig 8. Distribution and Relative Risk of ASCVD

Prehypertension May be considered a starting point in the cardiovascular disease continuum. Heribert Schunkert. NEJM, 2006

Research Design for Prehypertension Average Average 1992 1994 1996 1998 Hypertension Pre Hypertension (40%) Pre Hypertension Normal

Incidence ASCVD IHD Stroke Research Design for Prehypertension Average Average Follow-up 1992 1994 1996 1998 1999-2004 Hypertension Incidence ASCVD IHD Stroke Pre Hypertension (40%) Pre Hypertension Normal Normal

Baseline BP predicts progression to hypertension 4 year hypertension incidence rates Vasan RS Lancet 2001 KCPS Optimal = <120/80 mm Hg Normal = 120-130/80-85 mm Hg High Normal = 130-139/85-89 mm Hg

Impact of hypertension status on ASCVD risk in Korea Years

Impact of hypertension status on Stroke risk in Korea Years

Does Treating Prehypertension Decrease ASCVD Risk (1999-2004)?

JNC VI Lifestyle modifications Lose weight if overweight Limit ETOH (<1 oz/day) Increase aerobic exercise (30-40 min./day) Reduce sodium intake (<2.4gNa or 6g NaCl) Maintain potassium intake(> 90mmol/d K+) Maintain calcium and magnesium Stop smoking Reduce dietary saturated fat and cholesterol JNC VI Arch Intern Med 1997

결 론 (1) Population Attributable risk, PAR 한국인에서 고혈압은 전체 ASCVD 발생에 약 34% 기여한다. 한국인 Prehypertension 환자는 전체 ASCVD 발생에 약 13.2% 기여하며, 이는 고혈압의 10.3% 보다 크다. 특히 54세 이하 젊은 층에서 고혈압이 ASCVD 에 미치는 영향은 대단히 크다.

결 론 (2) 정상혈압(120/80)에 비해 Prehypertension 환자는 ASCVD risk 를 약 10-50% 증가시킨다. 정상혈압(120/80)을 110/70 이하로 낮추면 ASCVD risk 를 약 20% 줄일 수 있다. Prehypertension 환자가 정상혈압으로 개선되면 ASCVD risk 를 약 30-40% 낮춘다. Prehypertension 환자가 고혈압으로 발전하면 ASCVD risk 를 2배 (100%) 올린다. 따라서 고혈압은 물론이고, Prehypertension 에 대한 적극적인 치료, 관리, 예방이 필요하다고 생각된다.

감사합니다..