4 2007 ESH-ESC Guidelines SBP > 140 mmhg or DBP > 90 mmhg WHO definition of hypertensionin pregnancy 1. SBP > 140 mmhg or DBP > 90 mmhg 2. Rise in SBP > 25 mmhg or rise in DBP > 15 mmhg compared to pre-pregnancy values or those in the first trimester
8 Impact of Reproductive Hormones High Risk Events for Weight Gain Pre-menstrual cravings Pregnancy Lactation Perimenopausal Affect Preference for Macronutrients Affect Activity Levels Gynecoid versus Android Distribution American College of Obstetrics and Gynecologists 2008
9 Κίλδπλνη από ηελ ππεξβνιηθή αύμεζε ηνπ ζσκαηηθνύ βάξνπο Γ ηεο θπήζεσο Πξνεθιακςία Αχμεζε ΑΠ Απμεκέλνο θίλδπλνο ηνθεηνχ κε θαηζαξηθή. American College of Obstetrics and Gynecologists 2008
10 Obesity Preeclampsia - 4x highe 2x higher if women gain >3 kg between pregnancies Pregnancy-US studies 36% BMI>29 Κgr/ m² American College of Obstetrics and Gynecologists 2008
12 Θεξαπεία ηεο ππέξηαζεο ζηελ εγθπκνζύλε Με θαξκαθεπηηθή -- θαξκαθεπηηθή επίπεδα αξηεξηαθήο πίεζεο ειηθία θχεζεο ζπλππάξρνληεο παξάγνληεο θηλδχλνπ απφ ηελ κεηέξα θαη ην έκβξπν ESH 2009 ESC Guidelines on the managment of Cardiovascular Diseases during Pregnancy European Heart Journal, doi: 1093/eurheart / ehr 218
13 Με θαξκαθεπηηθή ζεξαπεία ΑΠ mmhg ε ΔΑΠ mmhg Γελ ππάξρεη βιάβε νξγάλσλ ζηφρσλ. Δξαζηεξηόηεηαο, θαηάθιηζε (αξηζηεξή πιάγηα ζέζε) Απνθπγή : Ειάηησζεο σκαηηθνύ βάξνπο θαη πξόζιεςεο άιαηνο ESH 2009 ESC Guidelines on the managment of Cardiovascular Diseases during Pregnancy European Heart Journal, doi: 1093/eurheart / ehr 218
15 How much total weight should I gain? This all depends on your prepregnancy wt: Kg for normal weight women BMI Kg for underweight women BMI < Kg for overweight women BMI Κg for obese women BMI>29 American College of Obstetrics and Gynecologists 2008
17 Οδεγίεο Και ηο ACOG ( American College of Obstetrics and Gynecologists) καθώρ και ηο ACSM (American College of Sports Medicine) ζςνιζηούν ηοςλάσιζηον 30λεπηη καθημεπινή άζκηζη. Η ζςμμεηοσή ζε άζκηζη όπυρ η κολύμβηζη, ηο πεππάηημα ή μικπήρ ένηαζηρ αεποβική δεν αςξάνοςν ηον κίνδςνο πηώζηρ. Η ΚΣ <140 ζθ /min, αποθςγή ςπεπθέπμανζηρ, ειδικά ζηο 1 ο ηπίμηνο και καλή ενςδάηυζη. American College of Obstetrics and Gynecologists 2008
19 Aληηππεξηαζηθά θάξκαθα ζηελ εγθπκνζύλε Γπλαίθεο κε πξνϋπάξρνπζα ΑΤ πξέπεη λα ζπλερίδνπλ ηελ αγσγή ηνπο εθηόο από ACE inhibitors and AIIA Curr Hypertens Rep 2001 Oct;3(5):392-9 European Heart Journal, doi: 1093/eurheart / ehr 218
20 Aληηππεξηαζηθά θάξκαθα ζηελ εγθπκνζύλε Central α-agonists β-blockers Α/β blockers Calcium-channel antagonists ACE inhibitors, ATII Diuretics Direct vasodilators a-methyldopa is the drug of choise Atenolol and metoprolol appear to be safe illate pregnacy Labetalol as a-methyldopa Oral nifedipine or I.V. isradipine in hypertensive emergencies Are contraindicated in pregnancy For chronic hypertension if patients are saltsensitive. Not in pre-eclampsia Hydralasine not the parental drug of choice. Curr Hypertens Rep 2001 Oct;3(5):392-9 European Heart Journal, doi: 1093/eurheart / ehr 218
23 Pregnancy complications Swedish Medical Birth Register, Normotensive Chronic hypertension n per 1000 n per 1000 Preclampsia, total Preclampsia, mild Preclampsia, severe Gestational diabetes Abruptio placentae Acta Obstet Gynecol Scand 2005;84:
24 Diagnosis Of pre-eclampsia it is a disease of signs 2 cardinal signs + or - Edema Hypertension + Proteinuria = Two facets of a complex pathophysiological process Uric acid: is elevated. Hypercalciuria. Doppler velocimetry to detect Uteroplacental hypo perfusion.
27 O. Papazachou, M. Daskalaki,..C. Thomopoulos, Th. Makris Helena Venizelou General & Maternity Hospital Dept. of Cardiology Athens, Greece ESC Paris 2011
28 Study population: recruitment and selection 615 consecutive pregnant women in 8 th week during the initial cardiological routine examination Medical History BP measurement IVF pregnancies (n=10) Anteconception hypertension(n=27) Anteconception Diabetes (n=8) 1 st visit office hypertension(n=21) Congenital heart disease (n=8 Other significant illness (n=6) 535 normotensive women without comorbidities Follow-up to the 26 th week Abortions (n=12) Incident diabetes in pregnancy (n=28) Lost during follow-up (n=35) 460 women underwent ABPM between the 26 th and 28 th week as well as to office BP measurements: to determine BP phenotypes Follow-up to delivery Assessment of study outcomes Preterm delivery and Preeclampsia
29 Classification of the study population according to BP phenotypes during 26 th 28 th week of pregnancy (early third trimester) 400 Normotensive BP phenotype n=364 (79%) White coat hypertension n=55 (12%) 250 NBP WCH 200 Masked hypertension n=18 (4%) MH SH Sustained hypertension n=23 (6%) % 12% 4% 6%
30 Multivariate logistic regression analysis OUTCOME: preterm delivery Determinants of the outcome p OR 95% confidence interval for OR Lower Upper Baseline Weight (Kg) Maternal Age (years) Primigravida Baseline Height (cm) Active smoking at baseline Gestational BP phenotype Normal BP REF White Coat HTN Masked HTN Sustained HTN <
31 Multivariate logistic regression analysis OUTCOME: preeclampsia Determinants p OR 95% confidence interval for OR Lower Upper Baseline Weight (Kg) < Maternal Age (years) Primigravida Baseline Height (cm) Active smoking at baseline Gestational BP phenotype Normal BP REF White Coat HTN Masked HTN < Sustained HTN <
53 Basic laboratory tests for monitoring hypertension in pregnancy Urinalysis Dipstick test for proteinuria has significant false-positive and false-negative rates. If dipstick results are positive (> 1), 24-h h urine collection is needed to confirm proteinuria. Negative dipstick results do not rule out proteinuria, especially if DBP > 90 mmhg. Proteinuria (24-h h urine collection) Standard to quantify proteinuria. If in excess of 2g/day, very close monitoring is warranted. If in excess of 3g/day, delivery should be considered.
54 Basic laboratory tests for monitoring hypertension in pregnancy Hemoglobin and hematocrit Hemoconcentration supports diagnosis of gestational hypertension with or without proteinuria. It indicates severity. Levels may be low in very severe cases because of hemolysis. Platelet count Low levels < 100,000 x 10 9 /L may suggest consumption in the microvasculature. Levels correspond to severity and are predictive of recovery rate in post-partum partum period, especially for women with HELLP syndrome.* * HELLP Hemolysis, Elevated Liver enzyme levels and Low Platelet count
55 Basic laboratory tests for monitoring hypertension in pregnancy Serum uric acid Elevated levels aid in differential diagnosis of gestational hypertension and may reflect severity. Serum creatinine Levels drop in pregnancy. Elevated levels suggest increasing severity of hypertension; assessment of 24-h h creatinine clearance may be necessary.
56 Basic laboratory tests for monitoring hypertension in pregnancy Serum AST, ALT Elevated levels suggest hepatic involvement. Increasing levels suggest worsening severity. Serum LDH Elevated levels are associated with hemolysis and hepatic involvement. May reflect severity and may predict potential for recovery post partum, especially for women with HELLP* syndrome. * HELLP Hemolysis, Elevated Liver enzyme levels and Low Platelet count
58 Our experience so far: preliminary data Masked hypertension in the early third trimester of pregnancy: prevalence and predictive value Objective: We aimed to determine the prevalence of masked hypertension in the early third trimester (26th 28th week) of pregnancy and its relation to preterm (<37 week) delivery and incident preeclampsia (N=615). Conclusion: Ambulatory BP monitoring in the early third trimester of pregnancy translated into diverse clinical phenotypes and among them the out-of-clinic hypertension including masked hypertension demonstrated an adverse effect on preterm delivery. In the same setting, masked hypertension was strongly related to the development of preeclampsia later in pregnancy ESC 2010
59 OBESITY Definition- pre-pregnant weight >30 Κgr/ m² How big a problem is this? Pregnancy-US studies 36% BMI>29 Κgr/ m²
61 T T T of Preeclampsia 3)Prevention of convulsions ( vide infra ). 4)Termination of pregnancy ( vide infra)
62 Pathophysiology Ischemic placenta Antigen production (cellular debris, special proteins)* Cytokines Maternal circulation 1. Lymphocellular activation 2. Nephrovascular endothelial activation Synergistic effect with increased hemodynamic load and maternal risk factors (e.g. diabetes mellitus) 1. Auto-Antibodies production activating ΑΣ1 receptor of ΑngII 2. Widespread endothelial dysfunction in tandem with enhancement of systemic inflammatory load * Fms-like tyrosine kinase 1, vascular endothelial growth factor, Soluble endoglin LaMarca, Hypertension 2010; AOP
63 Epidemiology of preeclampsia Incidence: Is a disease of humans only. Is the most common medical disorder complicating pregnancy 5-15% Is the most common hypertensive disorder in pregnancy. More common in primigravidas and elderly multipara. More common in winter. More in black races.
64 Epidemiology Risk factors Chronic hypertension. Chronic nephritis. Past history. Family history. Obesity. Multiple pregnancy. Stress Risk factors Polyhydramnios. Vesicular mole. Diabetes mellitus. Nulliparity. Teenage Pregnancy. Smoking.
66 Investigations Laboratory: Urine: 24 hour urine, Proteinuria. >0.3 g/24 hr Kidney functions: serum creatinine, urea, creatinine clearance and uric acid. Liver functions: bilirubin, Enzymes (SGPT and SGOT). Blood: CBC, HCt, Hemolysis and Platelet count (Thrombocytopenia). Coagulation Profile: Bleeding and clotting time HELLP syndrome hemolysis, high liver enzymes low platelets
67 Identity of the study California: ,403 pregnancies 481 (3.3%) Preeclampsia 266 died from CVD Median follow-up 37 years Median age of death 65 years Risk group Hazard Ratio CI Deaths PE 34w PE>34w No PE Xiaozhong et al. Hypertension 2011;57:48-55
68 2007 ESH-ESC Guidelines Measurement of BP Mercury sphygmomanometer Phase V to be recorded
69 Pre-eclampsia Gestational hypertension associated with significant proteinuria 300 mg/l or dipstick 2+ or more 500 mg/24 h or Poor organ perfusion Superimposed pre-eclampsia: It is the new development of Proteinuria after 20 weeks gestation in a patient with chronic hypertension
70 Cardiovascular changes in pregnancy Parameter Timing SBP DBP 4-6 mmhg 8-15 mmhg All bottom at wks, then rise gradually to pre-pregnancy values at term MAP 6-10 mmhg HR BPM Early 2nd trimester, then stable SV 10-30% Early 2nd trimester, then stable CO 33-45% Peaks in early 2nd trimester, then until term Main DM, Main EK: Obstetrics and Gynecology, 1984
71 Identity of the study California: ,403 pregnancies 481 (3.3%) Preeclampsia 266 died from CVD Median follow-up 37 years Median age of death 65 years Risk group Hazard Ratio CI Death s PE 34w PE>34w No PE Xiaozhong et al. Hypertension 2011;57:48-55
72 Hypertensive encephalopathy 1-2% of untreated essential hypertension SBP > 250 or DBP > 150 mmhg Treatment Mean BP by no more than 15-25% towards DBP mmhg Drug of choice: sodium nitroprusside Other drugs: nitroglycerin, nifedipine, labetalol ESH 2007
73 Eπείγνπζα ζεξαπεία ηεο ππέξηαζεο ζηελ εγθπκνζύλε ΑΠ 170 or ΔΑΠ 110 mmhg hydralazine?, labetalol, methyldopa or nifedipine nicardipine, sodium nitroprusside (risk of fatal cyanide poisoning with prolonged treatment), nitroglycerin ESH 2007 Cochrane Database Sysy Rev 2010 Nov10 ;11:CD00025Review European Heart Journal, doi: 1093/eurheart / ehr 218
74 Preeclampsia Results of Trials Given as Risk Differences Between Antihypertensive Treatment Groups Versus Control Groups Sibai 1984 diuretics Weitz 1987 methyldopa Sibai 1990 labetalol Sibai 1990 methyldopa Steyn 1997 ketanserian Favors Antihypertensive Favors Control
75 Incidence of the study outcomes Preeclampsia n=10 (2.2%) Preterm delivery n=55 (12%)* Including preeclampsia as cause in 8 cases 2 cases were considered mild and thus pregnancies proceeded without urgent delivery up to the 38 th -39 th week after hospitalization.
84 Conclusions The prevalence of masked hypertension in the early third trimester of pregnancy is 4% Masked hypertension predicts both preterm delivery and preeclampsia development. 24h BP identifies the masked gestational hypertensive phenotype and might be counseled in women in the early third trimester of pregnancy. Alternatively home BP measurements in the aforementioned period could constitute a better approach in this setting.
O R I G I N A L P A P E R Ε Ρ Ε Υ Ν Η Τ Ι Κ Η Ε Ρ Γ Α Σ Ι Α Hellenic Journal of Atherosclerosis 5(2):131 138 Ελληνική Επιθεώρηση Αθηροσκλήρωσης 5(2):131 138 Effect of nebivolol or nebivolol/ hydrochlorothiazide
Τι ςυμβαίνει μετά από την οξεία πνευμονική εμβολή; Σταφροσ Β. Κωνςταντινίδησ, MD, PhD, FESC Καθηγητήσ Καρδιολογίασ Δημοκρίτειο Πανεπιςτήμιο Θράκησ firstname.lastname@example.org Professor, Clinical Trials in Antithrombotic