Pulse pressure and risk of cardiovascular outcomes in patients with hypertension and coronary artery disease: an INternational VErapamil SR-trandolapril STudy (INVEST) analysis.
OBJECTIVE
The purpose of this study was to assess the relationship between pulse pressure (PP) and cardiovascular outcomes in a large, elderly, coronary artery disease (CAD) population with hypertension, and compare the predictive power of PP with other blood pressure measures.


RESULTS
In INternational VErapamil-trandolapril STudy, 22,576 CAD patients with hypertension (mean age 66 years) were randomized to verapamil-SR or atenolol-based strategies and followed for 2.7 years (mean). Primary outcome (PO) was time to first occurrence of death (all-cause), non-fatal myocardial infarction (MI), or non-fatal stroke. Mean follow-up PP was summarized by 5 mmHg subgroups for association with incidence of PO. Stepwise Cox proportional hazards models were used to estimate adjusted relative hazard ratios (HR) for the risk of PO with follow-up PP as a continuous variable, with linear and quadratic terms. Similar models were constructed for follow-up systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressures (MAP). A -2 log-likelihood statistic was used to assess the predictive power of PP compared with SBP, DBP, and MAP. For follow-up PP, the incidence and adjusted HR for the PO formed a J- or U-shaped curve. After adjusting for baseline covariates, both linear and quadratic terms for PP were significant (P < 0.0001 for both), with a nadir of 54 mmHg (bootstrapping 95% CI 42-60 mmHg). Similar quadratic relationships were found between PP and all-cause mortality or MI; the relationship between PP and stroke was linear. Pulse pressure was a predictor of PO even after including SBP (P = 0.007 linear term) or DBP (P < 0.0001 for both linear and quadratic terms) or MAP (P < 0.01 for both liner and quadratic terms) in the model. Using -2 log-likelihood differences, SBP (-2 log-likelihood difference 77.1 vs. 7.3 for PP), DBP (-2 log-likelihood difference 138.5 vs. 44.6 for PP), and MAP (-2 log-likelihood difference 125.0 vs. 13.4 for PP) were stronger predictors of PO than PP.


CONCLUSIONS
In CAD patients with hypertension, PP (on anti-hypertensive treatment) is a weaker predictor of cardiovascular outcomes than SBP, DBP, or MAP.
Division of Cardiology, Department of Medicine, Columbia University College of Physicians and Surgeons, St. Luke's-Roosevelt Hospital Center, 1000 Tenth Avenue, Suite 3B-30, New York, NY 10025, USA.
Sripal
S
Bangalore
Franz H
FH
Messerli
Stanley S
SS
Franklin
Giuseppe
G
Mancia
Annette
A
Champion
Carl J
CJ
Pepine
D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001262:Atenolol / Q000627:therapeutic use; D001794:Blood Pressure / Q000502:physiology*; D003324:Coronary Artery Disease / Q000188:drug therapy / Q000401:mortality / Q000503:physiopathology; D003327:Coronary Disease / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D008297:Male; D009203:Myocardial Infarction / Q000401:mortality / Q000517:prevention & control*; D011379:Prognosis; D020521:Stroke / Q000401:mortality / Q000517:prevention & control; D016896:Treatment Outcome; D014700:Verapamil / Q000627:therapeutic use*
D000959:Antihypertensive Agents; D001262:Atenolol; D014700:Verapamil