Dissertation committee:
Γεώργιος Στεργίου, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Εμμανουήλ Βαβουρανάκης, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Χαράλαμπος Βλαχόπουλος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Κωνσταντίνος Τσιούφης, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Κίμων Σταματελόπουλος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Αναστάσιος Κόλλιας, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Ευστάθιος Μανιός, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Summary:
INTRODUCTION: Blood pressure (BP) variability (BPV) is an inherent characteristic of BP and can be short-term (within 24 hours, from minute-to-minute to day/night variations, e.g., BP nocturnal dipping and morning surge), mid-term (over days), and long-term (over weeks, months, seasons, or years, including BPV among clinic/office visits) assessed with ambulatory (ABP), home (HBP), and office BP (OBP) measurements, respectively. All types of BPV are associated with adverse cardiovascular outcomes and the optimal treatment strategy regarding BPV is inadequately investigated.
AIM: The aim of the REducing blood pressure Variability in Essential hypertension with RAmipril vErsus Nifedipine GITS Trial (REVERENT) was to compare a dihydropyridine calcium channel blocker (nifedipine gastrointestinal therapeutic system [GITS]) vs an angiotensin converting enzyme inhibitor (ramipril) on different BPV indices and related hypertension mediated preclinical organ damage (HMOD), independent of the average BP reduction.
MATERIAL AND METHOD: This was a multicentre (three sites), international (China, Greece, Italy), prospective, randomized, open-label, blinded-end point study (PROBE) with 2 active treatment arms (Main Study duration 10 weeks), followed by open extension phase (Extension Study, overall duration of both phases 1 year. Adults with essential hypertension not receiving antihypertensive treatment were randomized to receive nifedipine GITS 30 mg or ramipril 10 mg and followed for 10 weeks (Main Study) or 1 year (Extension Study). Average BP, BPV and HMOD [carotid-femoral pulse wave velocity (cfPWV), albumin-creatinine ratio (ACR), estimated glomerular filtration rate (eGFR), carotid intima-media thickness (cIMT), and left ventricular mass index (LVMI)] indices were compared during two to four occasions during the study follow-up. BPV was assessed using standard deviation (SD) and coefficient of variation (CV).
RESULTS: Regarding the Main Study, 151 individuals were analyzed (mean age 53±10 [SD] years, males 58%, China/Greece/Italy 44/36/20%, baseline systolic OBP, HBP and 24h ABP 144±9, 138±10, and 143±10 mmHg, respectively). Regarding the Extension Study, 137 individuals were analyzed (mean age 52±10 years, males 61%, China/Greece/Italy 44/36/20%, baseline systolic OBP, HBP and 24h ABP 144±9, 137±10, and 143±10 mmHg, respectively). Average BP was reduced by all methods, with OBP presenting the largest reduction (20±13/10±7 mmHg systolic/diastolic baseline minus after 1 year of antihypertensive treatment, P<0.01). Average BP decline tended to be larger in the ramipril arm. BPV assessed with SD presented a reduction within the Main Study and then a gradual increase during the Extension Study for office BPV (-0.5±5.2/-0.3±2.5 mmHg, P=NS). Home BPV presented a large reduction (4.7±3.2/2.1±2.2 mmHg), while all aspects of ambulatory BPV did not show significant changes (-0.1±3.7/-0.1±2.4 mmHg for 24-hour weighted SD, P=NS), although there was a trend towards a decrease in ambulatory BPV with nifedipine and increase with ramipril. BPV assessed with CV presented a large decrease for HBP (3.0±2.4/2.1±2.7 mmHg, P<0.01) and an increase of different magnitude for all other methods of measurement. Home CV decrease was similar with both nifedipine and ramipril (3.0±2.2 vs 3.0±2.5 mmHg, respectively for systolic BPV, P=NS); while BPV increase in the other methods was generally larger and reached statistical significance in most cases for ramipril. The achieved BPV was consistently lower in the nifedipine arm. Regarding the HMOD indices, cfPWV, ACR, eGFR, cIMT, and LVMI, all were reduced during follow-up. cfPWV was significantly reduced in all individuals (0.6±1.1 m/s, P<0.01) without difference between nifedipine and ramipril. ACR and LVMI were significantly reduced only in the ramipril arm, while cIMT was significantly reduced only in the nifedipine arm. The degree of treatment-induced changes in BPV was not associated with the degree of HMOD change (regression or progression).
CONCLUSION: Nifedipine appeared to have more favorable effects on BPV changes than ramipril. No association of BPV changes with HMOD changes was observed within one year of treatment in this group of patients with low cardiovascular risk. Future research is needed to confirm the findings of the REVERENT trial.
Keywords:
Angiotensin converting enzyme inhibitors, Antihypertensive treatment, Blood pressure variability, Calcium channel blocker, Hypertension mediated organ damage, Nifedipine, Ramipril
