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1 고혈압환자관리의질향상방안 Hae-Young Lee, MD Seoul National University Hospital, South Korea

2 순서 고혈압조절의고위험군파악 생활습관조절의필요성 고혈압약제치료의개선방안

3 Obesity, aging and high salt intake: Triple threat against hypertension control in Korea Aging Obesity High salt

4 Am J Hypertens 2008; 21:

5 Higher blood pressure in patients with associated clinical conditions Current Status and Characteristics of Hypertension Treatment by Primary Physicians in Korea: Data from Korean Epidemiology Study on Hypertension (KEY Study) Kwang-Il Kim 1,2, Yooni Kim 3, Hee-Jin Kim 3, Duk-Hyun Kang 4, Jeong Bae Park 5, Dong-Ju Choi 1,2 and Cheol-Ho Kim 1,2 ; KEY Study Group SBP Percent DBP SBP-DBP 일반 140/90mmHg 당뇨병 130/80mmHg 신질환 130/80mmHg 전체

6 Age-specific and age-standardized prevalence of overweight or obesity (BMI 25 kg/m 2 ) Men Women BMI 25 kg/m 2 (%) * * * 0 Age Age 50 0 Age Age #

Prevalence of the Metabolic syndrome in KNHANES Percent (%) Percent (%) 70 60 50 40 30 20 10 0 70 60 50 40 30 20

2% Percent (%) 70 60 50 40 30 20 10 0 Men Women 20 30 40 50 60 70 80 Age (yr) 30.4% 2007 31.

7 Prevalence of the Metabolic syndrome in KNHANES Percent (%) Percent (%) Men Women Age (yr) Men Women Age (yr) 24.9% % Percent (%) Men Women Age (yr) 30.4% % Percent (%) Men Women Age (yr) Lim Soo, Kwang-Kon Koh et al. Diabetes Care 34: , 2011 #

8 Increased prevalence of metabolic syndrome parallel to BP elevation % % 26.1% 59.9% Metabolic syndrome (+) MetS (-) 20 0 Normotension Prehypertension Hypertension Lee HY, et al. International J Cardiol. 2012

9 Increased target organ damage in hypertensive population combined with metabolic syndrome Prevalence (%) * * MetS0 MetS(-)DM(-) MetS1 MetS(+)DM(-) 2 0 Stroke MI,angina CKD3 Stroke Myocardial infarction, angina Chronic renal disease Lee HY, et al. Kor J Hypertension, 2011

10 Obesity, aging and high salt intake: Triple threat against hypertension control in Korea Aging Obesity High salt

11 Aging Society in 2000 Aged Society in 2014

12 High prevalence of hypertension among elderly population About 2.5% (340,000 Pts) of HT Pts in KNHANES 3 are over > 80 years All M F 60 %

13 Decreased awareness, treatment and control rate in elderly hypertensive population

14 Exclusion of Pseudohypertension, Minimization of BP fluctuation Pseudohypertension a condition with a major discrepancy between intraarterial and arm-cuff BPs caused by sclerotic changes in media of the brachial artery BP should be measured at the wrist or finger Far more variable BP in the elderly more readings should be taken initially than for patients in the general population. BP should be measured in both the sitting and standing positions High frequency (as much as 30%) of a 20mmHg or greater fall in BP in patients with a systolic BP over 160 mmhg. Standing BP should be used to guide treatment decisions. Treatment of high blood pressure in elderly and octogenarians: European Society of Hypertension statement on blood pressure targets. BLOOD PRESSURE, 2016;25:

15 Thiazide-associated hyponatremia in the elderly Chronic hyponatremia causes fatigue, cognition impairment, gait deficits, falls and fractures and even increased mortality One study reported that 14% of thiazide-treated outpatients had hyponatremia (serum Na < 135 mmol/l), whereas age > 70 years was associated with a fourfold increase in hyponatremia risk. Only 10% of elderly hypertensive women with diuretic-associated hyponatremia received a low dose of hydrochlorothiazide (12.5 mg/day), suggesting that the effects of thiazides are dose-dependent. Even the low dose of indapamide (SR 1.5 mg daily) can induce severe hyponatremia (serum sodium < 125 mmol/l) in elderly individuals. Concominant administration of drugs affecting water homeostasis, such as SSRIs, NSAIDs or even benzodiazepines is important risk factors Thiazide associated hyponatremia in the elderly: what the clinician needs to know. Journal of Geriatric Cardiology. 2016;13:

16 Obesity, aging and high salt intake: Triple threat against hypertension control in Korea Aging Obesity High salt

17 High sodium intake in Korean population Sodium intake WHO 및우리나라최대섭취권고량 : 2,000mg 우리국민 1 인당하루나트륨섭취량 : 4,878mg(`10) = 12gram/day Increased sodium intake `07 년 `08 년 `09 년 `10 년 4,388mg 4,553mg 4,646mg 4,878mg

18 Renal pressure natriuresis is reset in salt-sensitive hypertension 6 Urinary Sodium Output and Intake (x normal) Normotension High Intake Normal Intake Hypertension Salt-Insensitive Salt-Sensitive Mean Arterial Pressure (mmhg)

19 동양인저레닌성고혈압빈도 1997 년 Komiya 등이일본인고혈압환자 741 명을대상으로한연구결과에의하면일본인에서의저 - 레닌고혈압의빈도는흑인및백인의빈도보다낮은 10-14% 인것으로나타났다 서양백인에서보고된저 - 레닌고혈압의빈도는약 25% 이다. 우리나라고혈압환자에서의저 - 레닌고혈압의빈도는 24% 로나타났다. 우리나라의저 - 레닌성고혈압의빈도를확인한기존소규모연구결과에서는박등에의한연구에서의빈도는 29.9% 로본연구에서의결과와비슷한양상을보이나, 서등의연구에서는이보다높은 47% 의빈도를보고하고있다.

20 Salt load test suggests that half of hypertensives might belong to salt-sensitive phenotype Rodriguez-Iturbe, et al. Am J Kidney Dis. 2007;50:

21 Same distribution of renin activity status as White Westerners observed in Korean HT population : Data from 1243 patients with essential hypertension visiting SNUH, Korea Prevalence (%) P= Total Male Female Low renin Medium renin ng/mL/hour High renin Lee HY, et al. Kor Hypertens J 2007

22 Clinical factors associated with Salt Sensitivity of blood pressure Age: loss of nephrons Race: African-Americans - kidney disease Genetic or familial: (e.g., Liddle s syndrome) Kidney Diseases: loss of nephrons Diabetes mellitus, insulin resistance Renin-angiotensin-aldosterone abnormalities: - low renin hypertension, primary aldosteronism

23 Low renin, salt sensitive phenotype significantly increases with age Prevalence (%) Log renin Low Medium High < > 65 Age Significant difference in renin activity between age groups, p < Age Correlation btw age and renin activity p < , r = 0.33 Lee HY, et al. Kor Hypertens J 2007

24 Salt Consumption was similarly high in the Northern Part of Japan in 1950s Year Population Sex Number Salt (g/day) Methods Authors 1950 Farmers M hr Urine A Fukuda 1951,52 City residents M hr Urine A Fukuda and Farmers F hr Urine 1953 Farmers M hr Urine M Takamatsu 1954 Farmers M hr Urine M Takamatsu 1956 Farmers M hr Urine T Mitsuhashi F hr Urine Source: Dr. S Kojima

25 However, salt consumption in Japan has decreased markedly to around 12-13g/day (about 15g reduction in 50 years) (g/day) years

26 Age- and sex-adjusted proportion of salt sensitivity according to metabolic status Metabolic syndrome and salt sensitivity of blood pressure in non-diabetic people in China. Lancet 2009;373:829-35

27 Greater BP response to high salt diet observed in metabolic syndrome

28 Sodium-sensitivity in obese hypertension is reversible by weight loss 250 vs 30 mmol Na+; 2-weeks Weight loss > 1 kg by 20-week program Weight excess is a main determinant of sodiumsensitivity of blood pressure Rocchini AP, NEJM 1989: 322: 476-7

Higher prevalence of HT among lower income population Population numbers Category of monthly income: 1=< 500,000 Won 2=500,000-1,000,000 Won, 3=1,000,000-1,500,000 Won 4=1,500,000-2,000,000

29 Higher prevalence of HT among lower income population Population numbers Category of monthly income: 1=< 500,000 Won 2=500,000-1,000,000 Won, 3=1,000,000-1,500,000 Won 4=1,500,000-2,000,000 5=2,000,000-3,000,000 6=3,000,000-4,000,000 7=4,000,000-6,000,000 8= > 6,000,000 Monthly incomes (2004, per capita income 17,260,000won/yr = 1,400,000 won/m) Hypertension Pre-hypertension Normal BP

30 Higher prevalence of HT among lower income population

31 Education as the most important explanatory variable of inequalities in hypertension in low-income population

32 No significant difference in obesity or diabetes mellitus according to income status

33 순서 고혈압조절의고위험군파악 생활습관조절의필요성 고혈압약제치료의개선방안

34 내용 : Issues on sodium intake 24 시간소변수집을통한나트륨섭취량평가 1 회소변, 혈액검사, 설문조사를통한 나트륨섭취평가가능성

35 24 시간소변수집을통한나트륨섭취량평가 첫아침소변을버리고모으기시작해다음날아침첫소변까지수집 24시간요크레아티닌으로적절히수집되었는지검정 20-25mg/kg/day ( 남성 ), 15-20mg/kg/day ( 여성 ) Underestimation: 검체소실등소변수집이부정확할때, 영양부족이나근육량이적은여성 Overestimation: 실제사구체여과율이저하된경우 Sodium excretion of 100 mmol/day for low sodium diet, and 200 mmol/day for high sodium diet.

36 설문을통한염분섭취량추정 :24 시간회상법 국민건강영양조사영양부문원시데이터의식품 및영양소섭취수준 개인별 24 시간회상법을이용하여조사 조리시에첨가된소금, 간장등양념의양을정확 하게측정하기어려움

37 식품교환표 / 식품성분표추정치와실측치비교 식품교환표 식품성분표 음식별절대값비교시식품교환표, 식품성분표로계산한나트륨추정치가모두실측치와유의한차이 양념이많은주요리, 부식, 국물요리에서큰차이 장류, 김치등의사용이많은한국음식에서추정치와실측치의차이가컸음

38 1 회소변측정을통한나트륨섭취량추정

39 1 회소변측정을통한나트륨섭취량추정 24-hr urine creatinine level was estimated based on the spot random urine creatinine. Cockcroft-Gault (CG) equation: 24-hr urine Cr level (mg) = {8 [0.2 age (yr)]} weight(kg), (if women, 0.85) 24-hr urine sodium level calculated XNA XNA = {spot urine Na (meq/l)/[10 spot urine Cr (mg/dl)]} x estimated 24-hr urine Cr level

40 1 회소변측정을통한나트륨섭취량추정의신뢰도 The correlation coefficients between the estimated and measured 24-hr urine Cr was 0.896, After estimating the 24-hr urine sodium levels, the correlation coefficients between the estimated and measured 24-hr urine sodium levels was The sensitivity to estimate the measured 24-hr urine sodium 100 meq/day using the estimated amount 100 meq/day was and 84.8%. In the Bland-Altman plot, the probability that the difference between the measured and estimated values existed within SD and+1.96 SD of the mean value was 95.5%

41 Use of a Single Baseline Versus Multi-Year 24-Hour Urine Collections for Estimation of Long-Term Sodium Intake and Associated CV Risk 574 subjects with 9, hour urine samples. Relative to a single baseline measurement, 50% of the subjects had a >0.8 gram sodium difference in sodium intake with long-term estimations. 45%, 49% and 50% of all subjects switched between tertiles of sodium intake when using 1, 5, or 15-year averages, respectively. Conclusions Relative to a single baseline 24-hour sodium measurement, the use of subsequent 24- hour urine samples resulted in different estimations of an individual s sodium intake, while population averages remained similar.

42 순서 고혈압조절의고위험군파악 생활습관조절의필요성 고혈압약제치료의개선방안

43 백의고혈압 (White coat hypertension) 정의 진료실혈압이 140/90mmHg 이상이고 활동혈압모니터상주간혈압이 135/85mmHg 미만일때

44 백의고혈압이배제안된상태의 initial combination therapy

45 Incidence rates and incidence rate ratios of cardiovascular events Incidence rates and incidence rate ratios of healthcare resource use

46 What is automated office BP (AOBP) technique?

9 mmhg lower than awake ambulatory BP. Mean awake ambulatory SBP in <120 mmhg target group at 27 months was 126.

47 AOBP is well-known to be significantly lower than conventional office BP measurement AOBP, awake ambulatory BP, home BP have the same range of BP measurement. In a SPRINT ABPM substudy, clinic BP (measured by AOBP method) in SBP <120 mmhg group was 6.9 mmhg lower than awake ambulatory BP. Mean awake ambulatory SBP in <120 mmhg target group at 27 months was mmhg, which is equivalent to a BP reading at least 10 mmhg higher in routine clinical practice. Blood Pressure Monitoring 2001;6: , J of Am Soc of HT 2016;10:

48 Follow-up of hypertensive patients After initiating anti-ht drug therapy, it is important to see the patient at 2- to 4-week intervals to evaluate the effects on BP and the possible side effects. Once the target is reached, a visit interval between 3- and 6-month is evidenced to be not different.

49 3 개월, 6 개월추적방문의차이 Patient satisfaction and adherence to treatment were similar in the groups. Bmj 2004

50 ㅠㅇㄹ 선생님, 1 달이상장기처방하면삭감되요.

51 장기처방에대한제도적지원이필요 짜장면은한달에한번정도만드시는게건강에좋습니다. 이번달에는또오시지마세요 매달같은진료비 x 4 회대비 (4 개월에 4 번방문 ) 대비 3 회분의진료비 x 3 회분의만성질환진료시간 (4 개월마다방문 )

52 새벽에혈압이오르는가면고혈압 Blood Pressure (mmhg) Beta Blocker ACE Inhibitor alpha-blocker Office BP 126/76mmHg Systolic BP Diastolic BP TIME

53 Masked Hypertension in Korean Epidemiology study on Hypertension II (KEY II) Observed in 940 / 5009 patients (21.2%) in 500 primary care clinics Risk factors Male gender (odds ratio 1.35, p = 0.049) Old age (odds ratio th Q vs 1 st Q, p = 0.004) Smoking (odds ratio 1.28, p = 0.014) No significant correlation with obesity, DM, MetS or FHx of CVD Prevalence and risk factors of masked hypertension identified by multiple self blood pressure measurement Hae-Young Lee, Jeong Bae Park, on behalf of KEY2 investigators Hypertension,

54 우리나라고혈압환자의고혈압약제수 3 종이상의처방례가외국보다적어, Difficult-to-treat 고혈압환자의치료가부족한경향을보인다 2017 년 1 월 SNUH 에서고혈압상병으로진료받은환자

55 2017 년 SNUH 에서고혈압상병으로진료받은환자의고혈압약제군 (%) * 병합요법의경우중복집계되므로합계가 100% 가넘음 2017 년 1 월 SNUH 에서고혈압상병으로진료받은환자

56 저용량에서 24 시간지속이어려운약제군의비율 (%) * 병합요법의경우중복집계되므로합계가 100% 가넘음 2017 년 1 월 SNUH 에서고혈압상병으로진료받은환자

57 ARB 처방례에서저용량대일반용량 / 고용량의비율 2017 년 1 월 SNUH 에서고혈압상병으로진료받은환자

58 Mean hourly BP change in ABPM 마스터제목스타일편집 Mean hourly ambulatory diastolic blood pressure (mmhg) Fimasartan 60 mg/d were associated with greater reductions in 마스터텍스트스타일을편집합니다 Least-squares mean reduction from baseline (mmhg) 둘째수준 셋째수준 Valsartan 80mg (n=29) DBP 넷째수준» 다섯째수준 Fimasartan 60mg (n=30) SBP ambulatory BP toward the end of the dosing interval compared with that with valsartan 80 mg/d, which resulted in higher individual and global T/P ratios. Mean hourly ambulatory systolic blood pressure (mmhg) Time after dose (h) Time after dose (h) Clin Ther. 2013;35(9):

59 요약 비만, 대사증후군, 노령화는혈압조절을가로막는중요방해요인이다. 염분섭취는여전히중요위험요인이며특히노인, 대사이상이동반될경우혈압상승의중요위험요인이된다. 저소득층의고혈압유병률, 발생률증가현상은당뇨병에서는관찰되지않는특성이다. 특히교육수준이떨어질경우위험성은증가한다. 3분진료, 무한경쟁체제의열악한의료환경에서백의고혈압이배제안된상태의강압제증량과, 반면충분한용량이처방되지않는상황모두환자순응도저하의큰요인이되고있다. 고혈압의효과적인조절을위해서는충분한설명과적정간격의진료가필요하며이에대해서는의사의윤리성에호소하는것보다제도적뒷받침이필요하다.

60 Thank you very much for your attention!

전립선암발생률추정과관련요인분석 : The Korean Cancer Prevention Study-II (KCPS-II)

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