HYPERLIPIDEMI Gleder og sorger ved behandling med sta;ner

Transkript

1 HYPERLIPIDEMI Gleder og sorger ved behandling med sta;ner Kje;l Re>erstøl Avdeling for ernæringsvitenskap, UiO Og Lipidklinikken, OUS- Rikshospitalet Tirsdag 16. februar 2016

2 Folke sykdommer Hyperlipidemi Hypertensjon Diabetes

3 2013 Kilde: Reseptregisteret

4 Forebyggende medisins dillemma Pasienten Frisk innà syk ut? Deilig nå kan jeg slappe av spise sunt nå? Uff da - er det så ille, må jeg virkelig bruke piller Legen Jeg = pillepusher? Pille på blå resept i stedet for å spise sunt? Må pasienten bruke piller?

5 Hvor mye skal man mase? Påfører vi pasientene unødig engstelse? Høy risk kan ikke føles. Har pasienten forstå>? Mul;farmasi Bivirkninger Compliance Medikalisering av samfunnet Varer resepten lenge nok? Tror du selv på behandlingsmålene? Har du definert et behandlingsmål for din pasient? Er du bli> enig med din pasienten om en ru;ne for oppfølging (eks 1-2 per år)

6 Verktøy for å nå behandlingsmål Vektøyet er: Kost og livss;l Medikamenter BT Lipider Blodsukker

7 I SCORE er høyrisiko definert som minst 5 % risiko for kardiovaskulær død de neste 10 år. Denne Den ;lsvarer omtrent en total hendelsesrate på 20 % basert på Framingham- funksjonen 137 sider

8 I primærforebygging kan man anse at lipidnivået er ;lfredss;llende dersom: totalkolesterol < 5,0 mmol/l LDL- kolesterol < 3,0 mmol/l HDL- kolesterol > 1,0 mmol/l (menn) eller > 1,3 mmol/l (kvinner) total- /HDL- kolesterol- ra;o < 5 triglyserider < 1.7 mmol/l

9 Hva er behandlingsmål? Meget høy risiko Høy risiko Moderat risiko Lav risiko Risiko kan beregnes/ es;meres på bakgrunn av risikokalkulatorer. Forskjellige styrker og svakheter ved de ulike kalkulatorene

10 Behandlingsmål ESC/EAS Guidelines 2011 For pasienter med meget høy CV risiko er anbefalt behandlingsmål basert på å ekstrapolere fra ;lgjengelige data: LDL <1,8 mmol / L eller minst 50% rela;v reduksjon i LDL

11 Eksempel Før Max sta;n Totalkolesterol 8,2 4,5 LDL- kolesterol 5,8 2,2 Triglyserid 2,6 1,7 HDL 1,3 1,3

12 Eksempel Max sta=n LDL - 63% Max sta=n & Ezi LDL - 21 % Totalkolesterol 8,2 4,5 3,9 mmol/l LDL- kolesterol 5,8 2,2 1,8 mmol/l Triglyserid 2,6 1,7 1,7 mmol/l HDL 1,3 1,3 1,3 mmol/l

13 Eksempel Totalkolesterol 8,2 mmol/l LDL- kolesterol 5,8 mmol/l Triglyserid 2,6 mmol/l HDL 1,3 mmol/l

14 Summary of Product Characteris;cs Atorvasta;n 80 mg: Rosuvasta;n 40 mg: total- C 46% LDL- C 61% triglycerides 33% total- C 46% LDL- C 63% triglycerides 28% h>p:// medicine/1424 h>p:// medicine/11976

15 Summary of Product Characteris;cs Among sta;n- treated pa;ents LDL- C: Eze;mib - 25% Placebo - 4% h>p://

16

17 Behandling av lipider ved diabetes

18 Sta;nbehandling ved diabetes Nasjonale faglige retningslinjer- diabetes. Forebygging, diagnos;kk og behandling

19 20-30% av høyrisikopasientene når behandlingsmålene for lipider

20 Hvorfor så mange over behandlingsmål? Stoler dere på behandlingsmålene? Guidelines og gjennomsni>spasienten Er det rik;g å pøse på med medisiner og formaninger Passer disse behandlingsmålene for min pasient?

21 Uoppdaget høy risiko Kolesterol 8 mmol/l BT 170 og / eller diast 100 mmhg 9 8,4 25 Prevalens % ,4 2,4 2,7 2,2 0,90,8 1,1 30 år år 75 år Menn Kvinner Prevalens % ,4 10,5 6,9 2,6 1,2 0,40,2 30 år år 75 år Menn Kvinner Tidsskr Nor Laegeforen Oct 4;127(19): Risk factors for myocardial infarction, stroke and diabetes in Norway.Graff-Iversen S, Jenum AK, Grøtvedt L, Bakken B, Selmer RM, Søgaard AJ.

22 Det finnes ikke lenger noe Statens helseundersøkelser Tar pulsen på Oslo-helsen Gratis helsesjekk. Statens helseundersøkelser inviterer bestemte aldersgrupper til en gratis helsesjekk. Resultatene kommer i posten. Personer født i 1924, 1925, 1940, 1941, 1955, 1960 og 1970 har fått invitasjon i posten.

23 Kostråd 2014

24 Main Protocol

25

26 Study design 0 yr 5 yr Interventio n Invitation letter S R 25,915 16,202 1,232 Control

27 Study Par=cipants Men years 16,202 men screened (65% of invited) Inclusion criteria in RCT: Total cholesterol mmol/l Healthy, no CVD, no hypertension (BP< 150 mmhg) CVD risk score upper 25% 79% smokers Not on a lipid lowering diet

28 Baseline characteris;ca N=1,232 Interven=on Control Age 45.2 (40-49) 45.2 (40-49) Smokers (%) Cigare>es/day 13.0 ± ± 9.9 Body weight 77.3 ± ± 9.8 Cholesterol (mmol/l) 8.36 ± ± 0.76 TG (mmol/l) 2.21 ± ± 1.1 TGs non- fas;ng (mmol/l) 2.80 ± ± 1.5 BP systolic (mmhg) ± ± 11.5 BP diastolic (mmhg) 81.4 ± ± 8.8 Diet score 14.8 ± ± 6.1

29 The interven;on Hjermann Individual talk in the interven;on group (10-15 min) Blood sampling Clinical examina;on ECG at screening Die;st (30 min) A diet record for each by a standardised ques;onnaire Dietary advice based on The diet record Body weight Serum cholesterol and triglyceride levels General background Adherence to diet was assessed at each follow- up examina;on in the interven;on group.

30 Study End Points Diagnos;c criteria strictly defined prior to start of study All CVD events were diagnosed by two cardiologists (blinded) Sudden death Death by first MI MI: Fatal, non- fatal, all combined Stroke: Fatal, non- fatal, all combined Total cardiovascular event

31 5 years RCT 604 Intervention 14* 16 Invitation letter S R 628 Control 3* 24 25,915 16,202 1,232 1,192

32 Study outcome

33 Diet interview at baseline and at 5- year follow- up. Random sample (n=300) in the interven=on group Reduction in cholesterol as the % reduction from the mean of 3 pre-randomisation values to the mean of the yearly values during the trial. In the highest quintile the mean cholesterol lowering was 23-5%, and in the lowest quintile 0-5%. Reduc;on in mean S- Cholesterol ( 5-23%) Reduc;on in mean S- Cholesterol ( 5-23%) Percent of subjects using items Baseline 5 Years Baseline 5 Years Cooking Polyunsaturated Oil 1, Polyunsaturted Margarine Bu>er or Saturated Margarine 80 1, On bread Sausage Meat Fat Cheese Fish Jam / Sweet Spread Bu>er or Saturated Margarine Polyunsaturated Margarine Low Fat, Low Caloric Margarine Milk Whole Milk Skimmed Milk Eggs per week 2,5 1 2,8 1,5

34 Saturated fat intake Interven;on group 8.2 E% Control group 18.3 E%

35 Stopped smoking Interven;on group 25% Control group 17% Interven;on group also reported decreased consump;on

36 S-Total cholesterol Mmol/L Mean difference for 5 years = 13% Years

37 Cumula=ve number of MI for 20 Years Holme I, Haaheim LL, Tonstad S, Hjermann I. Nutr Metab Cardiovasc Dis Jul;16(5):330-8

38 40 years follow up Risk of dying at first MI First event (number) Risk of dying at first MI compared to controls after 40 years HR=0.71 ( ; P=0.049)

39 Number of Death by first MI Number of Deaths by First MI Intervention Control years 8.5 years 15 years 40 years Years Since Randomization Risk for Death by First MI per Protocol AR RR

40 All- Cause Mortality Kaplan-Meier survival estimates Years of follow up Intervention Control

41 All- Cause Mortality Kaplan-Meier survival estimates Years of follow up All- cause mortality was decreased in the period 8 to 20 years after randomization but the curves overlapped the last 20 years Intervention Control

42 All- Cause Mortality Intervention (n=604) Control (n=628) Death by All Causes (number) years 8.5 years 15 years 25 years 40 years Years Since Randomization Risk Reduction RR AR (95% CI) (5.51, ) (6.49, ) (7.53, 0.41) (3.98, ) (3.15, )

43 Mean survival ;me increased 0.5 years (restricted due to censorship) in interven;on versus control and 0.9 years if an exponen;al distribu;on of survival ;mes was modeled for the rest of the life;me in the survivors

44 Conclusion Half- yearly advice on diet and healthy life style during a 5 year period can reduce mortality and give life long benefits.

45 Dødelighet av iskemisk hjertesykdom, menn <65 år

46 Kostråd i 1962 h>p:// _Ris_257049a.pdf

47 2014 Sales of butter in the U.S. rose 14 % in 2014 and climbed another 6 percent in the first three months of Sales of whole milk rose 11 % first half of 2015, while skim milk fell 14 %. Ref: Credit Suisse Research Institute 2015

48

49 RCT design

50 Totalmortalitet i 4S (sekundærprofylakse) Δ 36% Placebo Simvastatin

51 RCT design

52 Randomized Clinical Trials (RCT)- Challenges Medication 1. Standard dose is easy 2. Placebo is simple 3. Double- blind design is simple 4. Background exposure is usually comparable across na;onal borders (no ac;ve drug as background) 5. Taking a medicine does not mean taking less of something else 6. Compliance can be measured (coun;ng tablets, measuring drug in blood) 1. How measure the dose of dietary advice? 2. Placebo - food? 3. Double- Blinded design? 4. Dietary behaviour is different in countries / cultures / social classes 5. Increased intake of one macronutrient means less consump;on of another. What leads to an effect? 6. It's hard to keep a diet for many years. Compliance is difficult to measure and biomarkers are uncertain

53 Studiers beviskraft

54 Cofounders in prospec=ve co- hort studies?

55 Kostråd: Kunnskapsoppsummeringer IKKE enkeltstudier Me_et fe_ øker LDL- kolesterol og risiko for hjerte- og karsykdom sammenlignet med flerume_et fe_. WHO (1, 2), American Heart Associa;on (AHA) (3), Bri;ske Na;onal Ins;tute for Health and Care Excellence (NICE) (4), Australske Heart Founda;on (5), offisielle amerikanske kostråd (6) og offisielle europeiske myndigheter (EFSA) (7). Statens råd for ernæring (2011): «Utskiyning av me>ede fe>syrer med flerume>ede fe>syrer reduserer risiko for koronar hjertesykdom». Nordic Nutri;on Recommenda;ons (Nordisk ministerråd, 2012): Me>et < 10 E% (8). Nye amerikanske kostanbefalinger (2015): Me>et < 10 E% (9) REFERANSER: 1. Diet, Nutrition and the Prevention of Chronic Diseases. Report of a Joint WHO/FAO Expert Consultation. WHO. Technical Report Series No Geneva: World Health Organization, Fats and fatty acids in human nutrition. Report of an expert consultation, (2010). 3. Eckel RH, Jakicic JM, Ard JD, de Jesus JM, Houston Miller N, Hubbard VS, et al AHA/ACC guideline on lifestyle management to reduce cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129(25 Suppl 2):S NICE. Prevention of cardiovascular disease at a population level: Evidence on interventions to address dietary fats. NICE CVD guidance expert testimony paper 10 CVD EP10: National Institute for Health and Care Excellence, Australia HF. Summary of evidence. Dietary fats and dietary cholesterol for cardiovascular health. Heart Foundation Australia: Guidelines USD. Dietary Guideline for Americans. In: Services USDoAUSDoHaH, editor. Dietary Guidelines for Americans, th Edition, Washington, DC: U.S. Government Printing Office, December EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA). Scientific Opinion on Dietary Reference Values for fats, including saturated fatty acids, polyunsaturated fatty acids, monounsaturated fatty acids, trans fatty acids, and cholesterol. EFSA Journal 2010; 8:1461 [107 pp]. 8. Ministers NCo. Nordic Nutrition Recommendations 2012: Nordic Council of Ministers. 9. Committee TDGA. Scientific Report of the 2015 Dietary Guidelines Advisory Committee health.gov 2015 [cited ]. Available from:

56 Antall personer alderen 0-64 år med dødsårsaken hjerte-karsykdommer

57