Prevalence of hypertension is high Prevalence of hypertension (%) Kearney PM et al.,Lancet. 2005;365: Prevalence of hypertension in people aged 20 years and older
Curvilinear relation of blood pressure (BP) and cardiovascular risk. A meta-analysis of individual data for 1,000,000 adults in 61 prospective studies. Lancet 360:1903, 2002.
Absolute risks of CAD (left) and stroke mortality (right) for each decade of life by usual systolic blood pressure (BP) level A meta-analysis of individual data for 1,000,000 adults in 61 prospective studies. Lancet 360:1903, 2002.
Hypertension is a leading cause for cardiovascular morbidity MenWomenMenWomenMenWomenMenWomen Normotensive Hypertensive Coronary DiseaseStroke Peripheral Arterial Disease Heart Failure Biennial Age-Adjusted Rate per 1, Year Follow-up in Patients Aged Years 1,2 1. Kannel W.B. et al., JAMA 1996; 275: Kannel W.B. et al., J Hum Hypertens 2000; 14: 83-90
Global estimates suggest that less than 40% of hypertensives have both systolic and diastolic BP control, with similar estimates from the USA and other countries. Chobanian AV et al. The JNC 7 Report. JAMA 289, 2560–2571 (2003). Kearney P.M. et al. J Hypertens 22, 11–19 (2004). Mori H et al. Hypertens. Res. 29, 143–151 (2006). Rodriguez-Roca GC et al. Hypertens. Res. 32, 753–758 (2009).
USA 53.1 Canada 41.0 Mexico 21.8 Germany 33.6 Greece 49.5 England 29.2 Egypt 33.5 South Africa* 47.6 Japan* 55.7 Taiwan 18.0 China 28.8 Worldwide blood pressure control rates in treated hypertensive patients are low Kearney P.M. et al., J Hypertens 2004; 22: 11–19; * Data for men only Turkey 19.8
Prevalence of stroke by age and sex (NHANES: ). Source: NCHS and NHLBI. Prevalence of stroke
Approximately 795,000 people in the United States have a stroke each year, of which about 610,000 are a first attack; and 6.4 million Americans are stroke survivors. Stroke is also estimated to result in 134, 000 deaths annually and is the third leading cause of death in the USA behind heart disease and cancer. Stroke. 2011;42: ΑΓΓΕΙΑΚΟ ΕΓΚΕΦΑΛΙΚΟ ΕΠΕΙΣΟΔΙΟ
Stroke is the third leading cause of death worldwide HIV/AIDS = human immunodeficiency virus/acquired immune deficiency syndrome Reference: 1. World Health Organization. Global burden of stroke Available at: All deaths (%) Coronary heart disease CancerStrokeInjuryRespiratory tract infection HIV/AIDS
Κύρια αίτια θανάτου στην Ελλάδα-2005 (ανά πληθυσμού) ΑΕΕ ΣΝ Ca
Projections of stroke events in men and women in EU and EFTA countries, 2000 to 2025 ) Projections of stroke events in men and women in EU and EFTA countries, 2000 to 2025 (solely due to the demographic changes) European Fair Trade Association Iceland, Norway, and Switzerland, Truelsen T, et al, WHO, 2004
Impact of cardiovascular disease on life expectancy AMI, acute myocardial infarction Peeters A et al. Eur Heart J 2002;23:458–466. Atherothrombosis reduces life expectancy by approximately 8–12 years in patients aged over 60 years* Average remaining life expectancy at age 60, years (men) HealthyHistory of cardiovascular disease History of AMI History of stroke -7.4 years -9.2 years -12 years
Antihypertensive drug therapy is effective at reducing risk of CV events Heart failure 1 Fatal/Nonfatal stroke 1 Fatal/Nonfatal CHD 1 Risk reduction (%) 1. Moser and Herbert. J Am Coll Cardiol. 1996; 2. Collins R et al. Lancet Vascular deaths -52% -38% -16% -21%
Fatal and non- fatal events Mortality Fatal and non- fatal events Mortality Isolated systolic hypertension StrokeCHD All Causes CVNon CV StrokeCHD All Causes CVNon CV Systolic–diastolic hypertension <0.001 <0.01 NS Event reduction in patients on active antihypertensive treatment vs placebo or no treatment CHD: coronary heart disease; CV: cardiovascular Effective blood pressure control reduces cardiovascular morbidity and mortality Cifkova R, et al. J Hypertens. 2003;21:1011–1053. Relative Risk Reduction (%) ESH/ESC guidelines consider systolic values of <139 mmHg and diastolic values of <89 mmHg to be normal
Blood pressure reductions of as little as 2 mmHg reduce the risk of cardiovascular events by up to 10% Meta-analysis of 61 prospective, observational studies One million adults 12.7 million person-years 2 mmHg decrease in mean systolic blood pressure 10% reduction in risk of stroke mortality 7% reduction in risk of ischemic heart disease mortality Lewington S et al. Lancet. 2002;360:1903–1913.
7 κλινικές μελέτες vs. placebo ή χωρίς αγωγή υπερτασικοί >80 ετών Είναι ωφέλιμη η αντιυπερτασική αγωγή στους άνω των 80 ετών? Antihypertensive drugs in very old people: a subgroup meta-analysis of randomised controlled trials Lancet 1999:353: ΑΕΕ & Υπερήλικες (INDANA Study)
Treatment better ΑΕΕ (-34%) Ολική Θνητότητα (+6%- NS) Μείζονα ΚΑ συμβάματα (-22%) Καρδιακή Ανεπάρκεια (-39%) Double-blind All trials Gueyffier F et al. Lancet 1999:353: Control better Η αγωγή μειώνει τα ΚΑ συμβάματα αλλά όχι την ολική θνητότητα 0 Μετα-ανάλυση INDANA
N Engl J Med 2008;358: HYVET STUDY INDAPAMIDE PERINDOPRIL
N Engl J Med 2008;358: HYVET STUDY INDAPAMIDE PERINDOPRIL
There is no definitive evidence that that any class of antihypertensive agents offers special protection against stroke. There is a greater reduction in stroke risk with greater BP reduction. In most trials, however, the less- intensive therapy did not test a goal <140/90 mm Hg. Stroke (Feb);42:517–584. Lancet. 2003;362:1527–1535. BP & PRIMARY STROKE PREVENTION
Τhe JNC 7 report. JAMA. 2003;289:2560 –2572.
Recommendations 1.In agreement with the JNC 7 report, regular BP screening and appropriate treatment, including both lifestyle modification and pharmacological therapy, are recommended (Class I; Level of Evidence A) 2. Systolic BP should be treated to a goal of <140 mm Hg and diastolic BP to <90 mm Hg because these levels are associated with a lower risk of stroke and cardiovascular events (Class I; Level of Evidence A). 3. In patients with hypertension with diabetes or renal disease, the BP goal is <130/80 mm Hg (Class I; Level of Evidence A). Stroke (Feb);42:517–584.
BLOOD PRESSURE IN ACUTE STROKE Elevations in blood pressure > 160 mmHg are detected in >60% of patients with acute stroke. Both elevated and low blood pressures are associated with poor outcome after stroke. For every 10-mm Hg increase > 180 mm Hg, the risk of neurological deterioration increased by 40% and the risk of poor outcome increased by 23%. There are several questions about the management of arterial hypertension in the setting of acute stroke. Unfortunately, definite answers to these questions are not available yet. Stroke. 2007;38:
BLOOD PRESSURE IN ACUTE STROKE Theoretical reasons for lowering blood pressure include > reducing the formation of brain edema > lessening the risk of hemorrhagic transformation > preventing further vascular damage > forestalling early recurrent stroke Conversely, aggressive treatment of blood pressure may lead to neurological worsening by reducing perfusion pressure to ischemic areas of the brain. Excessively high blood pressure is associated with an increased risk of symptomatic hemorrhagic transformation. Stroke. 2007;38:
BLOOD PRESSURE IN ACUTE STROKE Vemmos et al found that among patients with most subtypes of ischemic stroke, elevated blood pressure was correlated with a past history of hypertension or severity of neurological impairments. They also found a U-shaped relationship between death and admission blood pressure. Both elevated and low admission levels were associated with high rates of early and late death. They also correlated death due to brain injury and brain edema with high initial blood pressure levels. Guidelines for the Early Management of Adults With Ischemic Stroke. Stroke. 2007;38: Vemmos KN et al. J Hum Hypertens. 2004;18:253–259.
AHA/ASA Recommendations for BP Management in Acute Ischemic Stroke 1. Patients eligible for treatment with intravenous thrombolytics or other acute reperfusion intervention and SBP >185 mm Hg or DBP >110 mm Hg should have BP lowered before the intervention. 2. A persistent SBP of >185 mm Hg or a DBP >110 mm Hg is a contraindication to intravenous thrombolytic therapy. 3. After reperfusion therapy, keep SBP <180 mm Hg and DBP <105 mm Hg for at least 24 hours. 4. Patients who have other medical indications for aggressive treatment of BP should be treated. Stroke. 2007;38:
AHA/ASA Recommendations for BP Management in Acute Ischemic Stroke 5. For those not receiving thrombolytic therapy, BP may be lowered if it is markedly elevated (SBP >220 mm Hg or DBP >120 mm Hg). 6. A reasonable goal would be to lower BP by approximately 15%-25% during the first 24 hours after onset of stroke. 7. In hypotensive patients, the cause of hypotension should be sought. Hypovolemia and cardiac arrhythmias should be treated and in exceptional circumstances, vasopressors may be prescribed in an attempt to improve cerebral blood flow. Stroke. 2007;38:
AHA/ASA Recommendations for BP Management in Acute Cerebral Hemorrhage 1. If SBP is >200 mm Hg or MAP is >150 mm Hg, consider aggressive reduction of BP. 2. If SBP is >180 mm Hg or MAP is >130 mm Hg and ICP may be elevated, consider monitoring ICP and reducing BP to keep cerebral perfusion pressure between 60 and 80 mm Hg. 3. If SBP is >180 mm Hg or MAP is >130 mm Hg and there is no evidence of or suspicion of elevated ICP, consider modest BP reduction (eg, MAP of 110 mm Hg or target blood pressure of 160/90 mm Hg). Stroke. 2007;38:2001–2023.
Lancet.Lancet Feb 26;377(9767): patients were allocated to treatment groups (1017 candesartan, 1012 placebo). During 6 months’ follow-up, the risk of the composite vascular endpoint did not differ between treatment groups (adjusted HR:1.09, 95% CI 0.84–1.41; p=0.52). Analysis of functional outcome suggested a higher risk of poor outcome in the candesartan group (adjusted common odds ratio 1.17, 95% CI 1.00–1.38; p=0.048).
Lancet.Lancet Feb 26;377(9767): The observed effects were similar for all secondary endpoints (including death from any cause, vascular death, ischaemic or haemorrhagic stroke, MI, stroke progression, and renal failure). There was no indication that careful blood- pressure lowering treatment with ARB candesartan is beneficial in patients with acute stroke and raised blood pressure. If anything, the evidence suggested a harmful effect.
Although numerous randomized trials and meta- analyses support the importance of treatment of hypertension for prevention of primary cardiovascular disease in general and stroke in particular, few trials directly address the role of BP treatment in secondary prevention among persons with stroke or TIA. A meta-analysis of randomized trials showed that antihypertensive medications reduced the risk of recurrent stroke after stroke or TIA. BP & SECONDARY STROKE PREVENTION Stroke. 2011;42:
The meta-analysis included 7 randomized trials performed through Together these trials included 15,527 participants with ischemic stroke, TIA, or intracerebral hemorrhage (ICH) randomized from 3 weeks to 14 months after the stroke event and followed up for 2 to 5 years. BP & SECONDARY STROKE PREVENTION Stroke. 2003;34:
Study; Quality Drug (daily dose); Control Other Antihypertensive Therapy, % Stroke Type, % Subjects (Centers) Follow-Up Interval, years Carter 1970; B Thiazide diuretic mg±methyldopa (750 mg); control ?“IS” (1)2–5 HSCSG 1974, A Deserpidine 1 mg and methylclothiazide 10 mg; placebo 0IS/ICH 96 TIA (10)2.8 Dutch TIA 1993; A Atenolol (50 mg); placebo?IS 66 TIA (56)2.6 PATS 1995; A Indapamide (2.5 mg); placebo 0IS (44)2 ICH 14 TIA 12 SAH 2 TEST 1995; A Atenolol ? mg; placebo?IS/ICH (21)2.5 TIA 20 HOPE 2000; A Ramipril; placebo64 † “Stroke” & TIA (267 † )5†5† PROGRESS 2001; A Perindopril 4 mg; placebo51IS (172)4.1 ICH 11 TIA 23 Perindopril 4 mg + indapamide 2.5 mg; double-placebo 50IS (172)4.1 ICH 11 TIA 22 Characteristics of Included Trials Stroke. 2003;34:
HOPE STUDY Η ραμιπρίλη μείωσε τον κίνδυνο εμφάνισης πρώτου ΑΕΕ Relative risk of stroke = 0.68 (P = ) Bosch et al. BMJ 2002;324:699–702 (P = ) 32%
HOPE: Major end-points RRR(%) with RAMIPRIL vs. PLACEBO
Randomised trial of a perindopril-based blood- pressure-lowering regimen among 6105 individuals with previous stroke or transient ischaemic attack PROGRESS Collaborative Group Lancet 2001; 358: Active treatment: combination of perindopril 4 mg/day and indapamide 2.0–2.5 mg/day at the physician’s discretion
Antihypertensive therapy in patients at risk of stroke: PROGRESS Compared with placebo, systolic/diastolic BP was reduced by an overall average of 9.0/4.0 mmHg (SE 0.3/0.2), with no evidence of attenuation Compared with placebo, combination therapy provided greater BP reductions than monotherapy (12.3/5.0 mmHg vs 4.9/2.8 mmHg) Significant reduction in stroke: 28% RRR (95% CI 17–38; p<0.0001) PROGRESS Collaborative Group. Lancet 2001;358:1033–1041.
Reductions in systolic and diastolic BP: PROGRESS Active treatment versus placebo R Follow-up (months) BP (mmHg) Systolic Diastolic Placebo Active Active = flexible regimen based on perindopril 4 mg/day with the addition of indapamide 2.0–2.5 mg/day at the physician’s discretion Reference: 1.PROGRESS Collaborative Group. Lancet 2001;358:1033–1041.
ΣΥΜΠΕΡΑΣΜΑΤΑ Cumulative incidence of stroke among participants assigned active treatment and those assigned placebo 28% μείωση του κινδύνου Lancet 2001; 358: PROGRESS STUDY Perindopril + Indapamide PROGRESS STUDY 28%
Events/patients Active a Placebo Favours active Favours placebo Secondary stroke Hazard ratio 1.0 Relative risk reduction (95%CI) a Active = Perindopril ± Indapamide. Total n=6105 PROGRESS: Secondary prevention in both hypertensive and nonhypertensive subjects 27% (8, 42%) 28% (17, 38%) 29% (16, 40%) 24% (9, 37%) 26% (16, 34%) 32% (17, 44%) Hypertensive 163/ /1452 Nonhypertensive 144/ /1602 Total stroke 307/ /3054 Major vascular events Hypertensive 240/ /1452 Nonhypertensive 218/ /1602 Total events 458/ /3054 Reference: 1.PROGRESS Collaborative Group. Lancet 2001;358:1033–1041.
Effects of study treatment on stroke and major vascular events in subgroups of patients Lancet 2001; 358: PROGRESS STUDY
Η μονοθεραπεία με περινδοπρίλη δεν μείωσε τη συχνότητα υποτροπής ΑΕΕ Reduction in relative risk of recurrent stroke (%) Blood pressure reduction (SBP/DBP, mmHg) 5/312/5 Perindopril 4 mg alone (n = 1,281) Perindopril 4 mg + Indapamide 2.5 mg (n = 1,770) PROGRESS Collaborative Group. Lancet 2001;358:1033–1041 P = ns P < 0.05 PROGRESS
Effects of study treatment on stroke subtypes, major vascular events, and deaths Lancet 2001; 358: PROGRESS STUDY
OutcomeTrialsEventsSubjects Rate in Control Group, %OR95% CIP Heterogeneity P Odds ratio (OR) and 95% confidence intervals (CI) determined using a random effects model. Stroke, all – Stroke, fatal – Stroke, nonfatal – Myocardial infarction, all – Vascular events, all – Death, vascular – Death, all – Effect of Lowering Blood Pressure on Stroke, Myocardial Infarction, All Vascular Events, and Death Stroke. 2003;34:
Effect of Drug Class, Prior Blood Pressure Status and Stroke Type on Stroke, Myocardial Infarction, and All Vascular Events Stroke. 2003;34: Outcome Stroke, All Trials/SubjectsOR (95% CI) MI, All Trials/SubjectsOR (95% CI) Vascular Events, All Trials/SubjectsOR (95% CI) All trials7/ (0.63–0.92)6/ (0.63–0.98)6/ (0.66–0.95) Drug class ACE-I2/ (0.75–1.14)2/ (0.56–0.98)2/ (0.61–1.13) β-RA2/ (0.72–1.20)2/ (0.60–1.45)2/ (0.81–1.27) Diuretic3/ (0.50–0.92)3/ (0.63–1.78)2/ (0.63–0.90) Diuretic and ACE-I 1/ (0.44–0.68)1/ (0.38–0.79)1/ (0.48–0.68) Non β-RA5/ (0.57–0.90)4/ (0.57–0.92)4/ (0.60–0.89) Baseline BP High blood pressure 3/ (0.45–1.22)……2/ (0.60–1.19) Any4/ (0.60–0.94)……4/ (0.63–0.97) Stroke type Ischemic stroke 2/ (0.24–1.40)……1/ (0.77–1.41) All stroke5/ (0.63–0.96)……5/13 955
Heterogeneity between drug classes in reducing recurrent stroke is apparent: β-receptor antagonists do not seem to reduce any vascular events Diuretics alone reduced stroke but not MI ACE-I reduced MI but not stroke ACE-I plus diuretic appears to be the most effective intervention
MOSES STUDY Stroke Jun;36(6): pts / Mean follow-up: 2.5 years
Systolic and diastolic blood pressure among patients assigned eprosartan (Epro) or nitrendipine (Nitren). Schrader J et al. Stroke 2005;36: MOSES STUDY
Η ερποσαρτάνη μείωσε τον κίνδυνο υποτροπής ΑΕΕ έναντι της νιτρενδιπίνης Schrader J et al. Stroke 2005;36:1218–1226. * * * P vs Nitrendipine † Includes recurrent events ††† MOSES STUDY P = P = * P = 0.061
MOSES STUDY Stroke Jun;36(6): pts / Mean follow-up: 2.5 years A reduction in TIAs accounted for most of the benefit in cerebrovascular events, with no significant difference in ischemic strokes, and a more traditional analysis of time to first cerebrovascular event did not show a benefit of eprosartan.
Kaplan–Meier Curves of the Cumulative Probability of Recurrent Stroke (Primary Outcome). Yusuf S et al. N Engl J Med 2008;359: ®
Kaplan–Meier Curves of the Cumulative Probability of a Major Cardiovascular Event or New-Onset Diabetes (Secondary Outcome). Yusuf S et al. N Engl J Med 2008;359: ®
® There was no significant difference in primary and secondary endpoints between patients on ASA with ER-DP or patients on clopidogrel and those on telmisartan and placebo. Telmisartan was not associated with a reduction in recurrent stroke (hazard ratio [HR], 0.95; 95% CI, 0.86 to 1.04; P=0.23) or major cardiovascular events (HR, 0.94; 95% CI, 0.87 to 1.01) during mean 2.5-year follow-up. More aggressive treatment with other antihypertensive medications in the placebo group reduced the difference in BP between the treatment groups (systolic BP differed by 5.4 mmHg at 1 month and 4.0 mmHg at 1 year) and may have reduced the impact of telmisartan treatment on stroke recurrence. N Engl J Med 2008;359:
After a 3-week, single-blind run-in period, patients underwent double-blind randomization, with 8576 assigned to receive 10 mg of ramipril per day, 8542 assigned to receive 80 mg of telmisartan per day, and 8502 assigned to receive both drugs (combination therapy). The primary composite outcome was death from cardiovascular causes, myocardial infarction, stroke, or hospitalization for heart failure.
ONTARGET STUDY N Engl J Med 2008;358:
ONTARGET STUDY N Engl J Med 2008;358:
Lancet 2008; 372: 1174–83 Patients intolerant to ACE inhibitors were enrolled if they had established coronary artery, peripheral vascular or cerebrovascular disease, or diabetes with end-organ damage. After a 3-week run-in period, 5926 patients, many of whom were receiving concomitant proven therapies, were randomised to receive telmisartan 80 mg/day (n=2954) or placebo (n=2972). The primary outcome was the composite of cardiovascular death, myocardial infarction, stroke, or hospitalisation for heart failure. TRANSCEND STUDY
Lancet 2008; 372: 1174–83 TRANSCEND STUDY
Lancet 2008; 372: 1174–83
TRANSCEND STUDY Lancet 2008; 372: 1174–83.
Guidelines for the Prevention of Stroke in Patients With Stroke or Transient Ischemic Attack 1. BP reduction is recommended for both prevention of recurrent stroke and prevention of other vascular events in persons who have had an ischemic stroke or TIA and are beyond the first 24 hours (Class I; Level of Evidence A). 2. Because this benefit extends to persons with and without a documented history of hypertension, this recommendation is reasonable for all patients with ischemic stroke or TIA who are considered appropriate for BP reduction (Class IIa; Level of Evidence B). Stroke. 2011;42:
Guidelines for the Prevention of Stroke in Patients With Stroke or Transient Ischemic Attack 3. An absolute target BP level and reduction are uncertain and should be individualized, but benefit has been associated with an average reduction of approximately 10/5 mm Hg, and normal BP levels have been defined as <120/80 mm Hg by JNC 7 (Class IIa; Level of Evidence B). 4. Several lifestyle modifications have been associated with BP reduction and are a reasonable part of a comprehensive antihypertensive therapy. These modifications include salt restriction; weight loss; consumption of a diet rich in fruits, vegetables, and low- fat dairy products; regular aerobic physical activity; and limited alcohol consumption (Class IIa; Level of Evidence C). Stroke. 2011;42:
Guidelines for the Prevention of Stroke in Patients With Stroke or Transient Ischemic Attack Stroke. 2011;42: The optimal drug regimen to achieve the recommended level of reduction is uncertain because direct comparisons between regimens are limited. The available data indicate that diuretics or the combination of diuretics and an ACEI are useful (Class I; Level of Evidence A). 6. The choice of specific drugs and targets should be individualized on the basis of pharmacological properties, mechanism of action, and consideration of specific patient characteristics for which specific agents are probably indicated (eg, extracranial cerebrovascular occlusive disease, renal impairment, cardiac disease, and diabetes) (Class IIa; Level of EvidenceB). (New recommendation).
Seven (7) studies met the inclusion criteria (including 114,009 participants). None of the studies was a randomised trial, six were cohort studies, and one a cross sectional study. Five of the seven studies reported a beneficial association between higher levels of chocolate consumption and the risk of cardiometabolic disorders. The highest levels of chocolate consumption were associated with a 37% reduction in cardiovascular disease (relative risk 0.63 (95% confidence interval 0.44 to 0.90)) and a 29% reduction in stroke compared with the lowest levels. Chocolate consumption and cardiometabolic disorders: systematic review and meta-analysis BMJ. 2011;343:d4488
NEW Guidelines for the Prevention of Stroke
5 Corti R, Flammer AJ, Hollenberg NK, Luscher TF. Cocoa and cardiovascular health. Circulation 2009;119: Balzer J, Heiss C, Schroeter H, Brouzos P, Kleinbongard P, Matern S, et al. Flavanols and cardiovascular health: effects on the circulating NO pool in humans. J Cardiovasc Pharmacol 2006;47(suppl 2):S Buijsse B, Feskens EJM, Kok FJ, Kromhout D. Cocoa intake, blood pressure, and cardiovascular mortality: the Zutphen Elderly Study. Arch Intern Med 2006;166: Buijsse B, Feskens EJ, Kok FJ, Kromhout D. Cocoa intake in relation to blood pressure and cardiovascular mortality in elderly men. Circulation 2006;113: Buijsse B, Weikert C, Drogan D, Bergmann M, Boeing H. Chocolate consumption in relation to blood pressure and risk of cardiovascular disease in German adults. Eur HeartJ 2010;31: Djousse L, Hopkins PN, Arnett DK, Pankow JS, Borecki I, North KE, et al. Chocolate consumption is inversely associated with calcified atherosclerotic plaque in the coronary arteries: the NHLBI Family Heart Study. Clin Nutr 2011;30: Faridi Z, Njike VY, Dutta S, Ali A, Katz DL. Acute dark chocolate and cocoa ingestion and endothelial function: a randomized controlled crossover trial. Am J Clin Nutr 2008;88: Grassi D, Desideri G, Necozione S, Lippi C, Casale R, Properzi G, et al. Blood pressure is reduced and insulin sensitivity increased in glucose- intolerant, hypertensive subjects after 15 days of consuming high-polyphenol dark chocolate. J Nutr 2008;138: Janszky I, Mukamal KJ, Ljung R, Ahnve S, Ahlbom A, Hallqvist J. Chocolate consumption and mortality following a first acute myocardial infarction: the Stockholm Heart Epidemiology Program. J Intern Med 2009;266: Mink PJ, Scrafford CG, Barraj LM, Harnack L, Hong CP, Nettleton JA, et al. Flavonoid intake and cardiovascular disease mortality: a prospective study in postmenopausal women. Am J Clin Nutr 2007;85: Mostofsky E, Levitan EB, Wolk A, Mittleman MA. Chocolate intake and incidence of heart failure: a population-based, prospective study of middle-aged and elderly women. Circ Heart Fail 2010;3: Oba S, Nagata C, Nakamura K, Fujii K, Kawachi T, Takatsuka N, et al. Consumption of coffee, green tea, oolong tea, black tea, chocolate snacks and the caffeine content in relation to risk of diabetes in Japanese men and women. Br J Nutr 2010;103: Allen RR, Carson L, Kwik UC, Evans EM, Erdman JW. Daily consumption of a dark chocolate containing flavanols and added sterol esters affects cardiovascular risk factors in a normotensive population with elevated cholesterol. J Nutr 2008;138: Desch S, Schmidt J, Kobler D, Sonnabend M, Eitel I, Sareban M, et al. Effect of cocoa products on blood pressure: systematic review and meta- analysis. Am J Hypertens 2010;23: Ding EL, Hutfless SM, Ding X, Girotra S. Chocolate and prevention of cardiovascular disease: a systematic review. Nutr Metab (Lond) 2006;3:2. 20 Grassi D, Lippi C, Necozione S, Desideri G, Ferri C. Short-term administration of dark chocolate is followed by a significant increase in insulin sensitivity and a decrease in blood pressure in healthy persons. Am J Clin Nutr 2005;81: Grassi D, Necozione S, Lippi C, Croce G, Valeri L, Pasqualetti P, et al. Cocoa reduces blood pressure and insulin resistance and improves endothelium-dependent vasodilation in hypertensives. Hypertension 2005;46: Hooper L, Kroon PA, Rimm EB, Cohn JS, Harvey I, Le Cornu KA, et al. Flavonoids, flavonoid-rich foods, and cardiovascular risk: a meta- analysis of randomized controlled trials. Am J Clin Nutr 2008;88: Jia L, Liu X, Bai YY, Li SH, Sun K, He C, et al. Short-term effect of cocoa product consumption on lipid profile: a meta-analysis of randomized controlled trials. Am J Clin Nutr 2010;92: Ried K, Sullivan T, Fakler P, Frank OR, Stocks NP. Does chocolate reduce blood pressure? A meta-analysis. BMC Med 2010;8:39 29 Allen R, Carson LA, Kwik-Uribe C, Evans EM, Erdman JW. Daily consumption of flavanol rich dark chocolate bar with added sterol esters improves cardiovascular markers in a population with elevated cholesterol. FASEB J 2007;21:A Balzer J, Rassaf T, Heiss C, Kleinbongard P, Lauer T, Merx M, et al. Sustained benefits in vascular function through flavanol-containing cocoa in medicated diabetic patients a double-masked, randomized, controlled trial. J Am Coll Cardiol 2008;51:
Lifestyle modifications for hypertension ModificationRecommendationExpected systolic reduction Weight reductionGoal of BMI 18–25 Waist <89cm 5–20 mmHg per 10kg wt loss DietFruits, vegetables, low-fat dairy products, less fat 8–14 mmHg Sodium restriction<2.4g every day2–8 mmHg Physical activity30 mins of aerobic 4 times a week 4–9 mmHg Reduced Alcohol (1/2 for women) 60–340ml beer, 300ml wine, 90ml 80proof whiskey in men 2–4 mmHg Reference: 1. Sacco RL Stroke 2006;37:577.
Το όφελος της λοσαρτάνης προκύπτει κυρίως λόγω της μείωσης των ΑΕΕ Dahlöf et al. Lancet 2002;359:995–1003 LIFE STUDY 9,193 pts with hypertension Losartan vs. Atenolol
92 HOT* Trial: BP Control Reduces Cardiovascular Events in Diabetics Hansson L, et al. Lancet. 1998;351:1755–1762. CV events* per 1000 pt years P = * Including MI, Stroke and CV deaths. Diabetes Subgroup Goal DBP (mmHg) Patients’ Number End SBP † (mmHg) End DBP † (mmHg) † End BP = Mean BP from the 6 th month of follow-up to the end of the study. *ΗΟT: Hypertension Optimal Treatment 51% reduction
– endpoint definition ® Primary endpoint Vascular events (stroke, MI or vascular death) Vascular events or congestive heart failure New onset diabetes Secondary endpoints Time to recurrent stroke Target is 1,715 strokes Diener HC, Sacco R, Yusuf S. Cerebrovasc Dis. 2007; 23: 368–380.
N Engl J Med Sep 18;359(12):
Stroke and cardiovascular events following TIA Survival free of event Stroke 10.5% All events 25.1% (Stroke, recurrent TIA, cardiovascular event, death) Days after TIA Reference: 1. Johnston et al. JAMA 2000;284:2901–2906
Cardiovascular Study in theElderly (CASTEL) European Working Party on High Blood Pressure in the Elderly (EWPHE) Coope and Warrender trial Systolic Hypertension in the Elderly Program Pilot (SHEP-P) Systolic Hypertension in the Elderly Program (SHEP) Swedish Trial in Old Patients with Hypertension (STOP) Syst-Eur 76% of participants were women The maximum age at baseline was 99 years. Τhe mortality rate was more than 20% Mean follow-up was 3·5 years. Less than 10% of patients were lost to follow-up in all trials Gueyffier F et al. Lancet 1999:353: Μετα-ανάλυση INDANA
(i) Strokes HDFP trial 102:158 MRC trial222:234 SHEP105:162 MRC trial101: others157:272 All trials525:845 (Heterogeneity X 2 4 = 4.2, NS) Treatment better Treatement worse 38% SD 4% reduction achieved 2p< Odds ratio (95% CI) (Treatment:Control) No. of events Treatment:Control Trial (or group of trials) Predicted reduction in stroke 35 40% Reference: 1.Collins R, MacMahon S. Brit. Med. Bull. 1994;52:272–290.
Antihypertensive treatment in patients with prior stroke/TIA: PROGRESS Cumulative incidence of stroke during 4-year follow-up Number at risk Active Placebo Follow-up (years) Proportion with stroke (%) Placebo Active Active = flexible regimen based on perindopril 4 mg/day with the addition of indapamide 2.0–2.5 mg/day at the physician’s discretion Reference: 1.PROGRESS Collaborative Group. Lancet 2001;358:1033–1041.