Makrovaskularna bolest Section 5 | 2 of 4 Curriculum Module III-7d | Cardiovascular disease Macrovascular disease is a very serious complication of diabetes and is the most common cause of premature death. It is very important to recognize that diabetes is much more than a blood glucose disease and to learn about how the macrovascular risk factors that contribute to this increased risk of morbidity and mortality can be identified and reduced. Slides current until 2008

Makrovaskularna bolest Koronarna bolest Cerebrovaskularna bolest Periferna vaskularna bolest Šta je to “događaj”? When talking of macrovascular disease, three main areas need to be considered: Coronary heart disease Cerebrovascular disease Peripheral vascular disease (PVD). PVD will not be discussed in this presentation as it has been dealt with in Section 5, Part 4 of 4. In order to interpret clinical trial results in this area of diabetes it is necessary to know what is meant by the term “event”. Most clinical trials discuss “the number of events reduced by an intervention”, therefore an “event” is usually a myocardial infarction (MI), or a stroke, and (but not in this context) angina or claudication. Slides current until 2008

Makrovaskularna bolest Glavni uzrok povećanog morbiditeta i mortaliteta u dijabetesu Osnovni poremećaj: ateroskleroza Macrovasular disease is the major cause of increased morbidity and mortality in diabetes. The underlying abnormality is atherosclerosis. Williams 1999 Slides current until 2008

Šta je ateroskleroza? Proces u kojem se naslage masnih supstancija, holesterol, otpadni produkti ćelijskog metabolizma i kalcijum ugrađuju u zid arterija. Ta formacija naziva se plak Plak može porasti dovoljno da značajno smanji protok krvi kroz arteriju. Akutni događaj dešava se kad on postane fragilan i rupturira Plak koju rupturira uzrokuje koagulum koji može blokirati protok krvi ili se otkačiti i na udaljenom delu tela uzrokovati srčani udar ili šlog Atherosclerosis comes from the Greek “athero” (gruel or paste) and “sclerosis” (hardness). It is the name of the process in which deposits of fatty substances, cholesterol, cellular waste products, calcium and other substances build up in the inner lining of an artery. This build up is called plaque. It usually affects large and medium-sized arteries.  Plaques can grow large enough to significantly reduce the blood flow through an artery. But most of the damage occurs when plaques become fragile and rupture. Plaques that rupture cause blood clots to form. These can block blood flow or break off and travel to another part of the body. If a coronary artery is blocked, it causes a heart attack. If it blocks a blood vessel that feeds the brain, it causes a stroke. If blood supply to the legs is reduced, it can cause difficulty in walking and eventually gangrene. Slides current until 2008

Koronarna bolest Poznati faktori rizika Životna dob Pol Porodična istorija Lipidni poremaćaj Hipertenzija Pušenje Dijabetes The typical risk factors for macrovascular disease are: 1. Age: as we grow older our risk increases 2. Gender: males are more at risk than females. However, women with diabetes lose their pre-menopausal protection 3. Family history: if a family history of heart attack or stroke is present then the risk is increased; therefore it is very important when talking with people with diabetes that we find out their family history and particularly if there are any members of the family that died at a young age (less than 65 years) of a heart attack or stroke 4. Lipid abnormalities: people with dyslipidaemia are more at risk 5. Hypertension: people with increased blood pressure are at increased risk 6. Smoking: it is particularly dangerous as tobacco smoke greatly increases atherosclerosis in the coronary arteries, the aorta and arteries in the legs 7. Diabetes: by itself it is also an independent factor for increased risk of macrovascular disease. Slides current until 2008

Koronarna bolest i dijabetes Češće i ranije se javlja kod osoba sa dijabetesom Etničke razlike Evropljani: više infarkta srca Kinezi/Japanci: više šlogova Žene gube polnu zaštitu Infarkt miokarda je često bezbolana (silent) Albuminurija povećava rizik od vaskularnog događaja Coronary heart disease occurs much more commonly in people with diabetes than in people without diabetes and occurs at an earlier age. There are ethnic differences in the rate and types of macrovascular disease. For example, Caucasians tend to have more myocardial infarctions (MI) whereas the Chinese and Japanese are more likely to have strokes. As mentioned earlier women with diabetes lose their gender protection. Due to an element of autonomic neuropathy some people with diabetes can have an MI and not know it - they do not feel the pain. This is called a silent MI. Another important factor is that people with diabetes who have an abnormal level of albuminuria are at much higher risk of a macrovascular event than those without albuminuria. They therefore need more intensive macrovascular risk reduction. Laing 1999 Slides current until 2008

Koronarna bolest i dijabetes U poređenju sa osobom bez dijabetesa one sa tipom 2 imaju: Isti rizik od srčanog udara kao osobe koje su ga već imale Dva do tri puta veći rizik od srčane slabosti Iznenadna srčana smrt događa se: - 50% češće kod muškaraca - 300% češće kod žena nego u grupi osoba bez dijabetesa slične životne dobi Haffner reported that people with type 2 diabetes have the same risk of having a heart attack as people without diabetes who have already had a heart attack. However, this finding is now being debated in the diabetes community. An under-recognized and under-treated condition in diabetes is heart failure (this will be discussed later in the presentation). Even more frightening statistic is that sudden death occurs 50% more often in men and 300% more often in women than in peers without diabetes of the same age. (Diabetes and cardiovascular disease: Time to Act, International Diabetes Federation, 2001). Haffner 1998 Slides current until 2008

Infarkt miokarda i dijabetes Osobe sa dijabetesom imaju goru prognozu čak i kad se uzmu u obzir veličina infarktne zone i faktori rizika People with diabetes have a worse prognosis than non-diabetic individuals even after adjustments for infarct size and risk factors. Slides current until 2008

Kontrola faktora rizika Istraživanja su pokazala povoljan efekat redukcije promenljivih faktora rizika za aterosklerozu Promenljivi faktori rizika aterosleroze su: Dislipidemija (posebno LDL ili "loš" holesterol) Pušenje i izlaganje duvanskom dimu Povišen krvni pritisak Dijabetes Gojaznost Fizička neaktivnost Men and people with a family history of premature cardiovascular disease have an increased risk of atherosclerosis. These risk factors cannot be controlled. However, research has shown the benefits of reducing the controllable risk factors for atherosclerosis. Diabetes health professionals have a very large role to play in assisting people with this. The controllable risk factors are: dyslipidaemia (see Slide 18 for target lipid levels); smoking tobacco and exposure to tobacco smoke; high blood pressure; obesity; physical inactivity; optimum blood glucose levels. Slides current until 2008

Razmatranje slučaja TJ je osoba sa novootkrivenim dijabetesom. Puši jednu paklicu cigareta na dan i ne bavi se fizičkim vežbanjem. Krvni pritisak mu je 150/95 mmHg a BMI 30. Koje faktore rizika on ima? Šta još treba ispitati? Kakav pristup biste imali prema njemu uzimajući u obzir faktore rizika? If time allows break the participants into small groups to discuss this case. After 10 minutes, ask for ideas from the groups. Slides current until 2008

Kontrola faktora rizika Promena stila života: prilagoditi ishranu, smaniti telesnu težinu, vežbati, prekinuti pušenje, popiti čašu crnog vina Lekovi koji snižavaju lipide ACE inhibitori Aspirin Koristi od kontrole glikemije? Lifestyle interventions: people with diabetes who are overweight need to lose about 10% of their body weight and reduce their saturated fat intake. While a lot of cholesterol is made in the liver, blood cholesterol can also be reduced by having a smaller intake of saturated and trans fats. The quality of the diet is essential. Things to consider are reducing total fat intake and replacing saturated and trans fats with monounsaturated fats, as well as increasing the intake of antioxidants and flavonoids. A glass of red wine per day has also been shown to increase HDL. (See Section 2.4 – Nutritional needs of people with type 1 diabetes and type 2 diabetes). Nutritional guidelines may have been developed in your country and you may want to look into these. Regular physical activity increases HDL cholesterol in some people. Ideally it should be recommended to do 30 minutes of exercise a day - but we know that this is often unrealistic for some people, particularly if they are very sedentary. A programme beginning with a 5-minute walk a few times a week may be a good place to start. The time and intensity of exercise should gradually increase. Lipid-lowering agents have proven very effective in reducing morbidity and mortality. Results from clinical trials will be discussed later in the presentation. Aspirin has been shown to be a cost-effective intervention in reducing risks. People should be encouraged to take a low dose of aspirin daily unless they have some contraindication such as gastric ulceration. Interestingly, while the benefits of tight glycaemic control in reducing microvascular complications have been unequivocally shown by the DCCT and UKPDS, the role of glycaemic control is less clear in reducing macrovascular risk. However, recent evidence from the EDIC study (follow-up of DCCT) for type 1 diabetes and from the UKPDS Post Monitoring Study for type 2 diabetes demonstrate a significant relationship between glycaemic control and a risk of macrovascular disease. NCEP 2005 Slides current until 2008

Koju dozu treba uzimati? Ko treba da preporuči aspirin? Upotreba aspirina Koju dozu treba uzimati? Ko treba da preporuči aspirin? Koja su neželjena dejstva aspirina? Koje su kontraindikacije? Postoji li neki drugi lek koji se može uzimati ako je aspirin kontraindikovan? Discuss these questions with the participants. Slides current until 2008

Diabetes Intervention and Complication Study (EDIC) Metabolička memorija Praćene su osobe koje su bile obuhvaćene DCCT. Razlika u glikoregulaciji izgubila se. Ukupno praćenje je 18 godina Researchers followed up the original DCCT cohort for 18 years. The resulting EDIC study has shown the concept of “metabolic memory”. Slides current until 2008

Diabetes Intervention and Complication Study (EDIC) Metabolička memorija Mikrovaskularne Makrovaskularne 57% reduction during EDIC follow-up period Despite the fact that the glycaemic control in both the DCCT intensive and conventional groups converged, people in the original intensive group still had significantly less micro- and macrovascular complications in the 18-year follow-up. Slides current until 2008

United Kingdom Prospective Diabetes Study (UKPDS) 30 Infarkt miokarda p=0.052 Konvencionalno 20 Intenzivno broj bolesnika (%) 10 30 30 Mikrovaskularni događaji p=0.0099 Šlog p=0.52 20 20 broj bolesnika (%) 10 broj bolesnika (%) 10 This slide shows the long-term complication outcomes of the UKPDS. Statistically, there are significant differences between the conventional and intensive arms in microvascular endpoints. However, there are no statistically significant differences between the groups for MI (p=0.052) or strokes (p=0.52). Therefore, the importance of glycaemic control in reducing macrovascular risk was inconclusive in type 2 diabetes at the time of the study in 1998. 3 6 9 12 15 3 6 9 12 15 Vreme od randomizacije (godine) Vreme od randomizacije (godine) UKPDS 1998 Slides current until 2008

Poststudijsko praćenje UKPDS Metabolička memorija: mikro- and makrovaskularne komplikacije Infarkt miokarda p=0.042, RR 0.86 (0.74-0.99) Mikrovaskularne bolesti P=0.0002, RR 0.72 (0.6- 0.86) However, similar to the DCCT metabolic memory results, the recently published Post Study Monitoring also showed that microvascular disease and myocardial infarction was significantly less common in those of the intensive arm of the UKPDS. The message from both DCCT and UKPDS is that not only does good control matter but good control at an early stage has significant long-term benefits in reducing both micro- and macrovascular complications. Slides current until 2008

Glavni prediktor KV mortaliteta LDL i HDL holesterol Dislipidemija Glavni prediktor KV mortaliteta LDL i HDL holesterol Lipidni profil kod tipa 2 dijabetesa povišeni trigliceridi snižen HDL povišene male guste partikule LDL The main predictors of cardiovascular disease mortality are LDL and HDL cholesterols. Raised triglycerides, low HDL and small dense LDL particles are a typical pattern of dyslipidaemia in type 2 diabetes. Slides current until 2008

Lipidi IDF – tip 2 dijabetesa LDL <2.5 mmol/L (<95 mg/dl) Triglyceride <2.3 mmol/L (<200 mg/dl) HDL cholesterol >1.0 mmol/L (>39 mg/dl) Kanada Primarni cilj Sekundarni cilj LDL-C </= 2.0 mmol/L TC:HDL-C <4.0 mmol/L SAD LDL <100 mg/dl Triglycerides <150 mg/dl HDL >40 mg/dl Targets for lipid levels in diabetes are very strict. Every effort should be made to assist a person with diabetes in reaching these targets. This should be done through adapting lifestyle and using statins and/or other lipid therapy. IDF 2005, CDA 2006, ADA 2004 Slides current until 2008

Lipidi: klinička ispitivanja Statini (lekovi koji snižavaju lipide) imaju dokazanu ulogu i u primarnoj i u sekundarnoj prevanciji A number of clinical trials over the years have shown the role of lipid-lowering agents. The statins or HMG Co A reductase inhibitors have an established role in both primary and secondary prevention. Another group of drugs called fibrates have been tested in a large multicentre randomized controlled clinical trial known as the FIELD study. The results from this study were disappointing as while fenofibrate therapy was associated with a reduction in total rate of cardiovascular events compared with placebo they did not reduce risk of death. Individuals should be maintained on their statin therapy. Scandinavian Simvastatin 1994 Slides current until 2008

Lipidi: neželjena dejstva statina Bol u mišićima (sa ili bez porasta enzima) Porast jetrenih enzima Rabdomioliza: češća kad se statini uzimaju zajedno sa fibratima Poremećaj sna i noćne more While statins are generally extremely safe drugs, there are some side effects that you should be aware of so you can warn your patient or alert the doctor. Statins on rare occasions can cause generalized muscle pain; this may require cessation of treatment. Statins can also raise the levels of liver enzymes. There is an increased risk of rhabdomyolysis if statins and fibrates are used in combination. As a safety precaution, if a person is taking this combination, the doctor should be alerted to this fact. Rhabdomyolysis is the breakdown of muscle. Some people also report cluster nightmares which can be very disturbing. Durrington 2000 Slides current until 2008

Upotreba lekova koji snižavaju lipide Koji lekovi postoje u našoj zemlji? Kako se ovi lekovi, kod nas, najčešće koriste? Ask for a group discussion on the use of lipid-lowering agents in the participants’ countries. Slides current until 2008

Hipertenzija i dijabetes Prevalenca Otprilike dvostruko veća nego kod osoba bez dijabetesa Češća kod muškaraca nego kod žena u grupi mađih od 50 godina Another risk factor for macrovascular disease is hypertension. Hypertension is twice as prevalent in people with diabetes compared to that in people without diabetes. Before the age of fifty, hypertension is more common in men than women. Slides current until 2008

Hipertenzija i dijabetes Gubi se dnevno/noćna varijacija krvnog pritiska može biti znak autonomne neuropatije Tip 1: normotenzivni dok se ne ispolji nefropatija Tip 2: hipertenzivni pre znakova bubrežnog oštećenja Our blood pressure normally varies from day to night, with daytime readings higher than at night. However, people with diabetes lose this variation. Hypertension in people with type 1 diabetes does not usually occur until they have renal disease. In people with type 2 diabetes, hypertension can occur before they have renal disease. Slides current until 2008

JNC 7 and ADA recommendations Hipertenzija JNC 7 and ADA recommendations Hipertenzija – krvni pritisak: ≥140/90mmHg Ciljni krvni pritisak kod osoba sa dijabetesom: 130/80mmHg Mnoge osobe moraju uzimati tri ili više lekova da bi postigle ciljne vrednosti krvnog pritiska The definition of hypertension is when the blood pressure is greater than 140/90mmHg. However, the target in diabetes is tighter than this and a blood pressure of less than 130/80mmHg is recommended. Achieving this can be difficult and it is common that three or more anti-hypertensive agents are required. However, common practice is that when the blood pressure is not reduced with one drug, the person is taken off that medication and a new one is tried. In reality what is needed is to keep adding antihypertensive agents to the regimen until the target blood pressure is achieved. ADA 2004, JNC7 Slides current until 2008

Lečenje hipertenzije Smanjiti unos soli ACE inhibitori i ARB imaju bolje efekat Izbegavati nesteroidne antireumatike Smanjiti alkohol u preporučene granice Prekinuti pušenje Preporuke iz DASH studije: Čineći jedno od navedenog snižavamo pritisak za 10 mmHg, što je dejstvo jedne tablete antihipertenziva As well as drug therapies there are several other strategies for reducing hypertension. These should be discussed with the people with diabetes who are hypertensive. They include: Decreasing salt: the ACE inhibitors and ARBs work more effectively if less salt is consumed. 2. Ideally people with diabetes should avoid taking non-steroidal anti-inflammatory medicines on a regular basis. They should replace them with regular paracetamol (acetominophen) and only take the anti-inflammatory drugs when there is exacerbation of arthritis. 3. Reducing alcohol intake will reduce blood pressure. (See Section 2.4 – Nutritonal needs in people with type 1 diabetes and type 2 diabetes). 4. Not smoking will also reduce blood pressure. Indeed reducing alcohol or salt can be the equivalent to a 10mmHg drop in blood pressure or one antihypertensive tablet. Slides current until 2008

Antihipertenzivni lekovi ACE-inhibitori (-prili) Blokeri A2 receptora (Lorista) Kalcijumski antagonisti (dihidropiridini: Norvasc, Amlopin, Nifelat retard ; nedihidropiridini: Verapamil, Diltiazem) Diuretici B-blockeri Almost all treatment in modern medicine, whether they are based on pharmacotherapy or not, have adverse reactions and side effects. Treatment of high blood pressure is no exception. This next series of slides will focus on some common side effects of anti-hypertensive medications. The classes of medication covered are outlined in the slide above. Slides current until 2008

Neželjeni efekti antihipertenziva ACE-inhibitori (hiperkaliemija, kašalj, otoci, porast kreatinina) Blokeri A2 receptora (otoci, porast kreatinina) The ACE inhibitors and the Angiotensin-2 receptor blockers are very closely related drugs. They act on different parts of the renin-angiotensin system, an important pathway in regulating intra-renal blood flow, fluid and electrolyte balance as well as blood pressure. As such, it is not surprising that raised creatinine (a measure of renal function) is an adverse reaction common to both classes of medications. A related side effect is raised potassium, also closely related to kidney function. A dry cough is an annoying, yet common side effect that is specific to ACE inhibitors. Those who suffer severely can be changed to A2 receptor blockers or other antihypertensives. Lastly, angioedema is an exceedingly rare but potentially fatal side effect of these agents, ACE inhibitors probably more commonly implicated than A1 receptor blockers. Patients should be told to watch out for swelling around the lips, tongue or throat, wheeze and shortness of breath. Should any of these symptoms appear on treatment, the medication should be immediately ceased and the patient asked to present to the nearest hospital. Slides current until 2008

Neželjeni efekti antihipertenziva Kalcijumski antagonisti Dihidropiridini: retencija tečnosti, flushing, tachycardia Nedihidropiridini: retencija tečnosti, opstipacija, bradycardia Calcium channel antagonists were previously very widely used, but have fallen out of favour slightly in recent times (especially the dihyropyridines). They are certainly very potent anti-hypertensives, but are not as effective at preventing mortality and morbidity as the previous two agents, especially the ACE inhibitors. The Calcium channel blockers can roughly be divided into two classes: the dihydropyridines (eg nifidipine, amlodipine) and the non-dihydropyridines (eg verapamil, diltiazem). The side effect profiles are different for each class. Dihypropyridines very commonly cause fluid retention and oedema. Sometimes this is so troublesome that cessation of the medication is necessary. Flushing is moderately common, but rarely severe enough to warrant cessation. Tachycardia can also occur. The non-dihydropyridines can also cause fluid retention, but also constipation. Bradycardia may occur, but is rarely dangerous unless beta-blockers are used concomitantly. Combinations of beta-blockers and non-dihyropyridines should therefore be avoided. Slides current until 2008

Neželjeni efekti antihipertenziva Diuretici: dehidratacija, hipokaliemija, impotencija Diuretics work by causing the kidneys to excrete fluid and electrolytes. Therefore it is not surprising that dehydration, low potassium and other electrolyte disturbances can occur when these agents are used. Impotence may also result from diuretic usage, and may worsen preexisting impotence from diabetes and vascular disease. Slides current until 2008

Neželjeni efekti antihipertenziva B-blockeri: asthma, klaudikacije, umor, impotencija Beta-blockers were previously contraindicated in diabetes, due to concerns regarding hypo unawareness. However, the UKPDS showed conclusively that beta-blockers are not only safe to use in diabetes, but are very effective in decreasing mortality and morbidity in people with diabetes. However, several contraindications do exist. They should never be used in asthmatics and will worsen claudication due to peripheral vascular disease. They quite commonly cause tiredness and impotence. Lastly, they may also worsen the lipid profile in people. Slides current until 2008

Koje su preporučene vrednosti krvnog pritiska kod nas? Hypertension Koje su preporučene vrednosti krvnog pritiska kod nas? Koji je najčešći pristup lečenju hipertenzije kod nas? If time allows, break the participants into small groups to discuss this activity. After 10 minutes, ask for ideas from the groups. Take this time to review the correct method for taking blood pressure: Importance of the correct cuff size Having the person sit down for 5 minutes Positioning of the arm Taking two or more readings 2 minutes apart and average them Making sure no caffeine or tobacco are consumed within 30 minutes prior to testing Having the automated meter calibrated at least yearly. Slides current until 2008

Rekapitulacija Makrovaskularna bolest Glavni uzrok ranog morbiditeta i mortaliteta Agresivna terapije dislipidemije i hipertenzije Intenzivno lečenje promenljivih faktora rizika životni stil: povećanje fizičke aktivnosti prilagođena ishrana: smaniti ukupne i zasićene masti, povećati mononezasićene masti, antioksidanse i flavonide In summary, macrovascular disease is a major cause of early morbidity and mortality in people with diabetes. In an attempt to reduce the risk of an event, it is very important to implement aggressive treatment of dyslipidaemia and blood pressure and all other modifiable lifestyle factors (physical activity and diet). Slides current until 2008 CDA 2003, ADA 2005

Evaluacioni test Koji od navedenih nalaza kod osobe sa dijabetesom nije faktor rizika za KV bolesti?  a. Visok nivo triglicerida b. Visok nivo HDL holesterola c. Visok nivo LDL holesterola d. Visok odnos ukupni holesterol/HDL holesterol Slides current until 2008

Evaluacioni test Koji od navedenih nalaza kod osobe sa dijabetesom nije faktor rizika za KV bolesti?  a. Visok nivo triglicerida b. Visok nivo HDL holesterola c. Visok nivo LDL holesterola d. Visok odnos ukupni holesterol/HDL holesterol Slides current until 2008

Evaluacioni test 2. Žena od 40 godina koja ima dijabetes tip 2 i gojazna je zabrinuta je jer je srčani udar čest problem u njenoj porodici. Koji bi od navedenih odgovora bio tačna informacija?  Samo muškarci sa dijabetesom treba da brinu o koronarnoj bolesti Premenopauzalne žene sa dijabetesom u većem su riziku od srčanog udara nego one koje nemaju dijabetes Ako smanjite telesnu masu do ciljnog nivoa rizik za srčani udar izjdednačiće se onome koji imaju žene bez dijabetesa Kada imate dijabetes, porodična anamneza o bolstima srca nije dodatni rizik za srčani udar Slides current until 2008

Evaluacioni test 2. Žena od 40 godina koja ima dijabetes tip 2 i gojazna je zabrinuta je jer je srčani udar čest problem u njenoj porodici. Koji bi od navedenih odgovora bio tačna informacija?  Samo muškarci sa dijabetesom treba da brinu o koronarnoj bolesti Premenopauzalne žene sa dijabetesom u većem su riziku od srčanog udara nego one koje nemaju dijabetes Ako smanjite telesnu masu do ciljnog nivoa rizik za srčani udar izjdednačiće se onome koji imaju žene bez dijabetesa Kada imate dijabetes, porodična anamneza o bolstima srca nije dodatni rizik za srčani udar Slides current until 2008

Evaluacioni test 3. Mušlarac koji ima tip 2 dijabetesa i hipertenziju ima krvni pritisak 162/94 nekoliko meseci pošto je počeo da uzima antihipertenzive. Šta je naredni korak u terapiji?  Dalje smanjivanje unosa masti u ishrani Test opterećenja Davanje dodatnog antihipertenziva Isključiti antihipertenzive koje uzima i zameniti ih drugima Slides current until 2008

Evaluacioni test 3. Mušlarac koji ima tip 2 dijabetesa i hipertenziju ima krvni pritisak 162/94 nekoliko meseci pošto je počeo da uzima antihipertenzive. Šta je naredni korak u terapiji?  Dalje smanjivanje unosa masti u ishrani Test opterećenja Davanje dodatnog antihipertenziva Isključiti antihipertenzive koje uzima i zameniti ih drugima Slides current until 2008

Evaluacioni test 4. Kod koje od navedenih osoba će aspirin biti kontraindikovan kao preventivna terapija? Stare osobe sa tipom 2 dijabetesa koje su imale trombotični šlog Žena od 19 godina koja ima tip 1 dijabetesa od 5 godina života Gojazna žena od 50 godina sa tipom 2 dijabetesa koja puši ali nema znake koronarne bolesti Muškarac od 38 godina sa tipom 1 dijabetesa i znacima koronarne bolesti Slides current until 2008

Evaluacioni test 4. Kod koje od navedenih osoba će aspirin biti kontraindikovan kao preventivna terapija? Stare osobe sa tipom 2 dijabetesa koje su imale trombotični šlog Žena od 19 godina koja ima tip 1 dijabetesa od 5 godina života Gojazna žena od 50 godina sa tipom 2 dijabetesa koja puši ali nema znake koronarne bolesti Muškarac od 38 godina sa tipom 1 dijabetesa i znacima koronarne bolesti Slides current until 2008

Odgovori b c Slides current until 2008

Literatura Williams G, Pickup JC. Handbook of Diabetes 2nd ed. London: Blackwell Science, 1999. Laing SP, Swerdlow AJ, Slater SD, Botha JL, Burden AC, et al. The British Diabetic Association Cohort Study, II: cause-specific mortality in patients with insulin-treated diabetes mellitus. Diabet Med 1999; 16: 466-71. Larsen J, Brekke M, Sandvik L, Arnesen H, Hanssen KF, et al. Silent Coronary Atheromatosis in Type 1 Diabetic Patients and Its Relation to Long-Term Glycaemic Control. Diabetes 2002; 51: 2637-41. Diabetes Control and Complications Trial, Epidemiology of Diabetes Interventions and Complications Research Group. Intensive Diabetes Therapy and Carotid Intima-Media Thickness in Type 1 Diabetes Mellitus. N Engl J Med 2003; 348: 2294-303. UK Prospective Diabetes Study Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes. Lancet 1998; 352: 837-53. Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease; the Scandinavian Survival Study. Lancet 1994; 344: 1383-9. Durrington P, Sniderman A. Hyperlipidemia 2000. Oxford: Health Press. US Department of Health and Human Services. The 7th Report of the Joint National Committee on prevention, detection, evaluation and treatment of high blood pressure.(JNC 7) National Institutes of Health, 2003. American Diabetes Association. Treatment of hypertension in adults with diabetes, Diabetes Care 2004; 27(suppl 1): S80-S82. Slides current until 2008

Literatura 10. Williams B, Poulter NR, Brown MJ, et al. Guidelines for management of hypertension: report of the fourth working party of the British Hypertension Society, 2004. BHS IV. J Hum Hypertens 2004; 18: 139-85. SHEP Cooperative Research Group. Prevention of stroke by antihypertensive drug and treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). JAMA 1991; 265: 3255-64. Birkenhager WH, Staessen JA, Gasowski J, de Leeuw PW. Effects of antihypertensive treatment on endpoints in the diabetic patients randomised in the Systolic Hypertension in Europe (Syst-Eur) trial. Nephrol 2000; 13(3): 232-7. Gerstein HC. Reduction of cardiovascular events and microvascular complications in diabetes with ACE inhibitor treatment: HOPE and MICRO-HOPE. Diabetes Metab Res Rev 2002; 18(suppl 3): S82-5. Heart Protection Study Collaborative Group. MRC/BHF Heart protection Study of cholesterol lowering with simvastatin in 2536 high-risk individuals: a randomised placebo controlled trial. Lancet 2002; 360(9326): 7-22. Haffner SM, Lehto S, Ronnemaa T, et al. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Eng j Med 1998; 339: 229-234. Canadian Diabetes Association. Dyslipidemia in Adults with Diabetes. Canadian Journal of Diabetes 2006; 30(3): 230-240. Slides current until 2008