Patients presenting with HF are more likely to be older and hypertensive, and more than half have a normal LV ejection fraction.210,220 Early investigations of patients with HF such as the Framingham Heart Study cited hypertension as the most frequent comorbidity; hypertension accounted for 39% of HF cases in men and 59% in women.217 In a population-based study in Olmstead County, Minnesota, 50% of patients presenting with new-onset HF had hyperten- However, recent randomized trials have probably under- estimated the contribution of hypertension to the development and progression of HF, possibly because elderly patients often are not included in clinical trials of HF. Of note, HF symptoms are rare in hypertensive individuals whose BP is well controlled at goal and who have not sustained an MI.222 6.3. Hypertension and HF Pathophysiology Initially, concentric hypertrophy of the LV compensates for pressure overload and normalizes systolic wall stress. This adaptive hypertrophy is accompanied by structural modifi- cations of the cardiac muscle, including alterations in gene expression, loss of cardiomyocytes, defective vascular development, and fibrosis. Thus, the compensatory response may transition to HF with progressive contractile dysfunc- In the second stage, CAD causes myocardial isch- emia or MI, which results in HF. BP falls as HF develops, so the contribution of hypertension to the HF syndrome may be underestimated. The mechanisms by which increased LV mass leads to depressed LV ejection fraction remain ill defined. Traditionally, an MI has been viewed as an obliga- tory event in the transition to depressed systolic function. 