Progress and Promise in RAAS Blockade

Overview Abbreviations: ACEI = angiotensin-converting enzyme inhibitor ARB = angiotensin II receptor blocker RAAS = renin-angiotensin-aldosterone system

CVD is the #1 cause of death in the US Despite significant advances in prevention and treatment over the past 50 years, cardiovascular disease (CVD) remains the leading cause of death in the United States for both women and men. In women, the number of deaths from CVD annually is greater than the combined deaths from the next 4 leading causes.

1 in 3 adults have 1 or more types of CVD CVD continues to impose a substantial medical and economic burden on society.

Relation of BP and age to IHD risk A meta-analysis of 61 prospective studies with over 12 million subject-years revealed that blood pressure (BP) throughout middle and old age is strongly and directly related to vascular (and overall) mortality, without any evidence of a threshold down to at least 115/75 mm Hg. At 40 to 69 years of age, each 20 mm Hg difference in systolic BP was associated with a 2-fold difference in the death rates from ischemic heart disease (IHD) (as shown here), as well as more than a 2-fold difference in the rate of death from stroke. Abbreviations: DBP = diastolic BP SBP = systolic BP

Both night-time and daytime BP are prognostically important: Rationale for 24-hour BP control An analysis of data on ambulatory BP monitoring from 7458 subjects (enrolled in prospective studies in 6 countries) found that night-time BP independently predicted total, CV, and non-CV mortality, as well as nonfatal outcomes, regardless of treatment status. Daytime BP independently predicted non-CV mortality, as well as the composite of fatal and nonfatal CV events, especially in untreated subjects. In contrast to commonly held views, daytime BP adjusted for night-time BP predicts fatal combined with nonfatal CV outcomes, except in treated patients in whom antihypertensive therapy might reduce BP during the day, but not at night. The findings provide a rationale for maintaining effective BP control over 24 hours.

HTN and the company it keeps The human and economic costs of hypertension (HTN) are staggering. HTN, ie, a BP reading of 140/90 mm Hg or higher, is associated with 69% of all first myocardial infarctions (MIs), 77% of first strokes, and 74% of cases of congestive heart failure (CHF). More than 90% of heart failure cases are preceded by HTN. The total direct and indirect costs of HTN for 2007 are estimated at $66.4 billion.

HTN commonly clusters with other risk factors A study of more than 57,000 HTN patients aged 35 years or older in a large managed-care organization, found that 56% of these individuals also had other risk factors for CVD that included diabetes, hyperlipidemia, and obesity, ie, a body mass index (BMI) of 30 kg/m2 or greater. In addition to HTN, 39% of the patients had 1 other risk factor (ie, diabetes, hyperlipidemia, or obesity), 14% had 2 other risk factors, and 3% had all 3 of these risk factors. Other findings of this study indicated that these additional risk factors (especially diabetes) substantially increased the risk of CVD events.

INTERHEART: Exponential rise in CVD with added risk factors INTERHEART, a global case-control study of risk factors for acute MI, was conducted in 52 countries on every continent with ~15,000 cases and controls matched for age and gender. The findings indicated that the same potentially modifiable risk factors account for most of the global risk of MI in all regions of the world. Current smoking and a high ratio of apolipoprotein (APO)B to APOA-1 were the 2 strongest individual risk factors. However, the odds for a first MI increased cumulatively with exposure to multiple risk factors. Abbreviation: CI = confidence interval