Overview to Antihypertensive and Lipid-lowering Therapies and Patient Care

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There are about 65 million Americans (or 20–25% of the population) with hypertension.As a top line figure that is probably a little low as it uses the rather strict definition of high blood pressure as being 140 over 90.Hypertension is also very strongly age-related, and as we get older that frequency goes up a lot. Essentially, 95% of Americans will be hypertensive in their lifetime. It is a very common problem.Moreover, if we use a blood pressure of 120 over 80 as being the cut-off point, which is a harsher limit but nevertheless one that will probably get adopted, then more than half of Americans are hypertensive; by age 50 or 60 it is the rule rather than the exception.

It is a very common disease and we have been aware of it for a long time, but it is still difficult to say exactly why people get high blood pressure. It starts as an increase in blood flow and ends up as a constriction of arteries, causing resistance to blood pumped from the heart and as a result the arteries harden. It is initially a physiologic rather than an anatomic problem and probably has a lot to do with salt increase and weight gain and the sedentary lifestyles that most Americans lead. If you look at societies where people catch lunch rather than order it, then the rise in blood pressure with age is a lot less marked and hypertension is not so common.

Impact of Hypertension

The economic impact of hypertension is huge. We talk about cardiovascular disease in the US as costing US$200 billion a year. That covers heart disease, hypertension and stroke. It is hard to separate out hypertension as it is an integral part of both stroke and heart disease, but the direct cost is probably in the region of US$75-100 billion. Indirect costs in terms of work loss and the human experience are much more.

Socially, the costs are equally hard to determine. While hypertension is one of, or the, major cause of kidney disease, dialysis, stroke, and heart failure, the sad news is that until an event such as this appears there are few symptoms other than perhaps something non-specific such as headache or dizziness. It is no surprise that hypertension is also known as the silent killer; it can go on for a long time—the first symptoms may be stroke or heart attack. This is why it is so critical to get regular blood pressure checks.

Hypertension Treatment Options

There are two main ways that hypertension can be treated. Since so much hypertension is caused by obesity and inactivity, they are the obvious first targets for lifestyle changes including dietary regimens and exercise programs. At the same time you have to start medication. We are now learning that it is critical to start medicine earlier than we have been doing. A recent study—TROPHY (TRial Of Preventing HYpertension)—looked at individuals at 'pre-hypertension' levels, who have blood pressure in the 130–140 range where most doctors would not recommend medication. Subjects were treated for two years, and researchers witnessed a 60% drop in progression to overt hypertension.1 This raises the possibility that one of our greatest mistakes is to wait until blood pressure is too high; we ought to treat it much earlier.

There are a number of classes of drug that target hypertension. The most common are calcium channel blockers, diuretics, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor-blockers (ARBs) and alpha blockers. They offer a whole range of possibilities. As with the cause of hypertension, the way the treatments work is a little bit of a mystery. Diuretics eliminate salt and decrease the volume of blood initially. After a while they no longer have the diuretic effect but yet the blood pressure still stays down, which is a little bit of a mystery. Similarly the ACE inhibitors block conversion to angiotensin-II, but after a while intrinsic ACE levels rise again but blood pressure does not go up.

Most of these treatments are cheap. Diuretics are very inexpensive, and are also very effective in African Americans, which is an important consideration. ACE inhibitors have additional benefits for patients with heart failure and/or diabetes, and their major side effect is cough.ARBs are similar to ACE inhibitors but do not result in cough and are slightly better tolerated. ARBs are, however, quite expensive as they are still under patent. There are other niche drugs—such as alpha blockers—when you have failed the four major categories. Some are mild but others, like monoxodil, are vasodilators and very powerful drugs that can bring almost anybody's blood pressure down.

Hypertension and High Cholesterol

The truth of the matter is that if you have one risk factor you are more likely to have another.This has been known about for 50 years and is at least in part because the substrate is the same (poor diet, lack of activity, etc). It is important to note that these risk factors in combination are far more devastating than they are by themselves; elevated cholesterol and hypertension may each bring a 10% increase in risk of cardiovascular disease, but if you have both your risk has not risen by 20%, it is more like 30–40% increased.They have synergistic adverse effects. Conversely, treating both hypertension and cholesterol has greater than expected results.

This has important implications for patient management. Where you have a patient who has presented with one risk factor, it is vital to investigate whether they have others.The presence of two or more factors is ominous, and patients should be treated more intensively with lower targets for blood pressure and cholesterol levels, for example. Nevertheless, we can do the most good for the patient with multiple risk factors. And the treatments for the different elements of cardiovascular risk do not interact.

The current guidelines for treatment of these conditions focus on the identification of risk, and to then match the intensiveness of the therapy (both lifestyle changes and medications) to the global risk of cardiovascular disease of the individual.This is carried out using the Framingham risk assessment table, which takes account of age, blood pressure, smoking status, weight, and other factors, to derive a ten-year risk and therefore determine how aggressive treatment should be. The previous approach was to count up the number of individual risk factors.

A few years ago the cholesterol level was set at 70mg/dl (or 1.7mMol) of low-density lipoprotein (LDL). Blood pressure levels have changed to acknowledge this new condition of 'prehypertensive', defined as being 120-140 over 80-90.While at first there was resistance to prehypertension on the grounds that it was creating a nondisease, this is falling away to be replaced by the opinion that recognizing it is foresightful, and that early intervention can save lives.

Further Progress

Now, in the 21st century,we have the technology and the knowledge to tackle cardiovascular disease. The challenge now is to educate medical carers and the population at large; to convince them of the real risk that we face and of the benefit of early intervention. In the US, the average patient will have their blood pressure attended to by one physician, their cholesterol levels by another and perhaps their diabetes by a third. For things to improve we need to consolidate this care and make everyone responsible.

One of the newer ideas is metabolic syndrome, defined by a patient having three out of five risk factors: high triglyceride levels; high levels of LDL/low levels of high-density lipoprotein (HDL); high blood pressure; abdominal obesity (specifically measured by waistline);and abnormal fasting blood sugar. There is a common pathophysiology for these conditions of increased inflammation and oxidative stress and decreased endothelial function. While there is still some controversy about whether this is a genuine condition, there are real examples of metabolic syndrome. We only need to look at former President Bill Clinton who appeared happy and healthy, but was a walking time bomb: he had high blood pressure, high tri-glycerides, high blood sugar levels, a large waist, and low HDL. It was no surprise that he needed a quadruple heart bypass. He was very lucky to survive.

For the immediate future, there will be more combination therapy, and guidelines will change to acknowledge more aggressive treatment that will start earlier. Our problem is not a lack of drugs at the moment, it is how and when we implement them.


  1. Kaplan NM, Trial of Preventing Hypertension (TROPHY): design and 2-year progress report , Hypertension (2004) Aug;44(2): pp. 125-126.
    Crossref | PubMed