Let's start off with something that you already know. This is from the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7). It's important to understand that there are many risk factors for cardiovascular disease (CVD) and 2 notable additions to the list are here. The first is the metabolic syndrome. The other is presence of kidney disease, specifically microalbumineria, which is probably similar to C-reactive protein (CRP) in terms of giving you a signal of inflammatory markers of the vasculature and glomerular filtration rate (GFR) of less than 60.

This is the patient who has a problem and doesn't know it. He is so averse to exercise, but he loves his dog so he buys a treadmill for his dog, because he doesn't want to walk the dog! He's sitting in a chair 6 feet from the television, drinking his regular Coke. Heaven forbid that he lean over and change the channel. He's got the remote control on the armchair. This is what we have to deal with and it's a real problem.

Now this is a classic paper. It's quoted in the JNC 7 and, in addition, it's something that you need to know. Blood pressure is a continuum. If you go from 140 mm Hg to 139 mm Hg, your risk does not go away all of a sudden. I think that's an obvious but important point that you need to know.

I want you to focus on the left side of the slide for systolic blood pressure. You'll notice that at ages 40 to 49, going all the way up to ages 80 or 89, the risk goes down to 115 mm Hg. So there is increased risk if you go above a systolic blood pressure of 115 mm Hg. In fact, with a 20-millimeter increase, you double cardiovascular risk within any of those age ranges. So just keep that in mind. I think that's an important point and it really brings home the message that you need to get to blood pressure goal.

Now, there are clinical trials that support the concept that a little goes a long way. I've summarized them for you here. Five- to 10-millimeter differences do make a difference in cardiovascular risk, and for that matter, in kidney outcomes.

In the United Kingdom Prospective Diabetes Study (UKPDS), a 10 mm Hg difference did make a difference in terms of cardiovascular events. In the captopril trial in type 1 diabetes, there was not a huge difference in blood pressure but enough to make a statistically significant difference. In the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack (ALLHAT) trial, the angiotensin-converting enzyme (ACE) inhibitor group had the highest blood pressure, but there was no difference from the other groups in primary outcome. But when you look at secondary outcomes, there clearly were differences. The Heart Outcomes Prevention Evaluation (HOPE) trial, an important trial epidemiologically, clearly showed in a subgroup of very sick people, a blood pressure difference of 17/10 mm Hg clearly made a difference.

In fact, here are the data from the UKPDS, showing you very nicely that for blood pressure control, over on the right side of the screen, you have tremendous risk reductions just by lowering blood pressure. Notice, it's not even less than 140 mm Hg, but it's certainly less than 154 mm Hg, and clearly, there is risk benefit across the board for any diabetes endpoint, diabetes-related death, stroke, or microvascular end points -- all are reduced by anywhere from 30% to 40%.

These are data from the Reduction of Endpoints in NIDDM With the Angiotensin II Antagonist Losartan (RENAAL) trial in individuals with type 2 diabetes and advanced nephropathy. Here you can see that if you lower the blood pressure to less than 140 mm Hg, you have tremendous benefits in terms of the relationship for the primary composite end point, which was time to dialysis, doubling of creatinine, or death. So again, there is a clear benefit in terms of lowering to the blood pressure goal, approaching the blood pressure goal, and risk benefit.

This is a summary of the world guidelines. It's a busy slide, but you can see that people are trying to focus on differences amongst guidelines. The differences are really subtle and I think they're different just because people like writing guidelines and they want to say there's something different about it! The reality is that, at least in the northern hemisphere, everybody is agreeing that if you have diabetes or hypertension with kidney disease, then less than 130/80 mm Hg is your goal blood pressure, and you should be starting with an ACE inhibitor or an angiotensin receptor blocker (ARB). The asterisk stands for the need for additional therapy in most cases. In fact, diuretics are reasonable additional drugs to achieve blood pressure goals.

In the ALLHAT trial, if you don't look at it carefully, the implication is that this is a monotherapy trial. I'm sure you're all aware that it's not a monotherapy trial. In fact, there was an average of 2 drugs given to each patient and many of the patients got more than 2 drugs. The primary end point is here -- absolutely no difference.

Now, is there really a clear superiority of one blood pressure drug class over another? The answer is no. The definitive data are right here. If you look at comparisons and cardiovascular outcomes for various treatments based on differences in blood pressure the reality is that, in general, there are no differences.

The Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial is important because the hypothesis was there would be a difference in the outcome favoring the ARB if blood pressure control was the same. You'll notice the primary end point of this trial was not different.

Now of course people walked away saying: well, there's no difference. Well, just a minute -- the hypothesis was that blood pressures were the same. I want you to look at the bottom panel. The bottom panel shows that within the first 3 to 4 months of the trial, there were huge differences in blood pressure between the groups, favoring amlodipine. It took a while to catch up because this was a trial starting with monotherapy (the old-fashioned way) and then other drugs were slowly added. Now we're in the 21st century and hopefully we're more advanced than that. But 30% of the events in this trial occurred during this period when blood pressures were totally unequal. So it's a very important point to keep in mind when you're looking not only at evaluation of trials, but also when you're taking care of patients. You do not have the luxury of waiting 9 months or a year to get to the blood pressure goal. You need to get there quickly, especially in older people because they are susceptible, especially to stroke.

In clinical trials we do an excellent job of getting to goal blood pressure. Here are the data from clinical trials achieving goal blood pressure. It's about double what we do based on the National Health and Nutrition Examination Survey (NHANES) data. In clinical trials, they do pill counts on the patients, and if it's off you've lost patients. It's worse than bill collectors if you're in the clinical trial! You need to follow the rules; it's very simple.

That's not happening in clinical practice. There needs to be time in the office where the physician can communicate with the patient; the patient gets educated, gets involved, understands what's expected of him, and then everybody's on the same page. That's not happening, and that's a real missing link in terms of achieving goal blood pressures.

This is a summary of clinical trials looking at how many drugs you need to reach blood pressure goal. You can see that the old number used to be 3.2 and it's now about 2.9 -- it hasn't changed much. This is an important point.

There's a linear relationship, not only with blood pressure and cardiovascular events, but also with cholesterol and cardiovascular events. This is taken from the updated Adult Treatment Panel (ATP) III guidelines that were published in Circulation very recently.

With glucose, it's the same benefit: as hemoglobin A_1c goes down, you get fewer cardiovascular events. Again, this is a very important point to keep in mind with regard to hemoglobin A_1c. This is not just true for blood pressure. It's true for all cardiovascular risk factors that are known to have a major impact in renal functioning.

The Action to Control Cardiovascular Disease in Diabetes (ACCORD) trial is funded by the National Institutes of Health. It's looking at 10,000 diabetics and it's asking, what is the level of blood pressure we should be achieving? They're randomizing to 2 levels of systolic blood pressure, less than 120 mm Hg and less than 140 mm Hg, and hemoglobin A_1c less than 6% and less than 7.5%. This trial is fully recruited and the results will be known in early 2009. I'm happy to tell you that they are in fact getting to blood pressure goals of less than 120 mm Hg. It is requiring 3 to 4 drugs and maximal doses of those drugs, and it is requiring major patient participation, but they are doing it. So again, there is evidence that they can do it in a trial. There's no reason that you can't do it in your office with appropriate time and resources.

Now here's our report card. These are the data from NHANES 1999-2000 in yellow compared with NHANES III. It looks at patients with diabetes and how good a job we're doing. If you look at hemoglobin A_1c of less than 7%, you can see that if anything, we're getting worse, not better, in terms of the people achieving goal. If you look at blood pressure, we got a little better, but we're still well below 50%. If you look at cholesterol, even that's below 50%. In fact, if you go over to the far right and look at the yellow bar, we have a number of people with all 3 factors controlled to goal -- 7.3%. Now that's failure in anybody's book. One hundred percent is not what we're looking for here, but at least 50% or 60% is going to be a huge benefit in terms of cardiovascular risk reduction at a societal level.

There's a big problem. There's a failure to titrate or use combination medications despite knowing the patient is not at goal. This is important and it represents clinical inertia that must be overcome. That was put in the JNC 7 and basically what it says is there are recalcitrant physicians out there who don't want to give more drugs. They don't want to increase the dose. They're either afraid of more phone calls, side effects, or all of the above. So physicians are part of the problem. Lack of time to educate the patient is also a major problem because the patient doesn't know any better, so they're not pushing anything. It's a multifactorial problem.

This last slide says it all. These are data published in The New England Journal of Medicine from the Steno Diabetes Clinic in Copenhagen. They have their standard treatment, which isn't bad. And then they decided to get very aggressive and they had an intensive treatment group. This was a group in which hemoglobin A_1c counts were lowered to close to 6.5%, the systolic blood pressure was less than 130 mm Hg, the low density lipoprotein (LDL) cholesterol was below 100, everybody got an aspirin, and they were on lifestyle modification. Yes, people did participate and they did get lowered values, very close to all of those values -- and they got a 20% absolute risk reduction. That means they reduced the risk of a cardiovascular event in that group with intensive treatment 20% below the conventional treatment group. The conventional treatment group, by the way, is doing a lot better than the NHANES data that I showed you. So we have a long way to go in terms ofgetting where we need to be in terms of achieving goals.