Monday, August 17, 2009

Fatty Liver, Inflammation, and Hypertension

In earlier posts, I've stressed the fact that the vast majority (90-95%) of all cases of hypertension diagnosed are "essential hypertension"--that is, hypertension with no known cause.

Increasingly, however, it appears that many cases of hypertension may in fact be cases of high levels of inflammation in the body--in particular, cases of inflammation of the liver.

When large amounts of fat are stored in the liver, the liver becomes stressed. This raises the level of several liver enzymes, and has been strongly associated with hypertension.[1]

Metabolic Syndrome, or Syndrome X, commonly has has high blood pressure as a key marker. The early stages of Metabolic Syndrome are characterized by high blood levels of insulin. Insulin raises blood pressure, so the linkage between Metabolic Syndrome and hypertension might seem to be obvious; but as Metabolic Syndrome progresses into Type II diabetes, the pancreas becomes unable to provide insulin, and blood insulin levels plummet. If it were insulin levels alone causing the hypertension, we would expect that as people became diabetic, their blood pressure would fall--but instead, the opposite occurs, and blood pressure usually worsens with the onset of diabetes.

The real culprit may be fatty liver, which is common in Metabolic Syndrome and in Type II diabetes (indeed, some researchers now feel that fatty liver is one of the hallmarks of Metabolic Syndrome). The mechanism by which fatty liver causes increases in blod pressure has only recently been discovered. As fat accumulates in the liver, the liver becomes inflammed. In response, it releases C-Reactive Protein (CRP). CRP is one of the classic markers of inflammation; for example, it rises sharply when the body is fighting an infection. CRP's role in cardiovascular disease is controversial, and CRP testing has been shown to be a poor predictor of heart disease or stroke. [2]

CRP is, however, intimately involved in hypertension, and recent research shows how CRP circulating in the bloodstream acts upon the arteries to raise blood pressure. [3]

Fatty liver disease is traditionally divided into two flavors--Alcoholic Fatty Liver Disease (AFLD), and Non-Alcoholic Fatty Liver Disease (NAFLD). The only difference between the two, however, is that NAFLD is not attributed to overconsumption of alcohol; the condition of the liver is indistinguishable in the two diseases. When the liver becomes highly inflamed, AFLD is called alcoholic hepatitis, while NAFLD progresses into Non-Alcoholic Steatohepatitis (NASH). NAFLD was only recently recognized as a specific disease, but it is widespread: in one major study, one-third of adults were discovered to have fatty livers (defined as a liver-fat content of 5.5% or more), although the prevalence varied considerably by ethnic group. [4]

NAFLD is considered by some to be mainly a metabolic disease--part of Metabolic Syndrome--while others consider it to be simply a disease of obesity. Since obesity is one of the hallmarks of Metabolic Syndrome, this may be a moot distinction.

Almost everyone is now familiar with the fact that those who accumulate fat around their stomachs are at greater risk for heart disease than those who accumulate fat around their hips--the so-called "apple" and "pear" patterns of fat storage. This turns out not to be quite accurate. Samuel Klein, a leading researcher on the connection between liver problems and cardivascular disease, says, "Abdominal fat is not the best marker for risk. It appears liver fat is the real marker. Abdominal fat probably has been cited in the past because it tends to track so closely with liver fat. But if you look at people where the two don't correspond — with excess fat in the liver but not in the abdomen and vice versa — the only thing that consistently predicts metabolic derangements is fat in the liver." [5]

Klein goes on to say, ""Fatty liver disease is completely reversible. If you lose weight, you quickly eliminate fat in your liver. As little as two days of calorie restriction can improve the situation dramatically, and as fat in the liver is reduced, insulin sensitivity and metabolic problems improve."

The linkage between fatty liver and hypertension is an important research result, because most cases of fatty liver can be cured--by the patient, without medication or medical intervention. Weight loss of five percent of body weight shows quick improvement in liver fat accumulation and insulin resistance, while a loss of nine percent of body weight or more appears to reverse liver damage. [6,7].

Even moderate levels of exercise also have a powerful and rapid effect on reversing fatty liver, even without substantial weight loss. [8,9].

I'll have more on this topic in my next post.

[1] Stranges, Saverio, et al. Body Fat Distribution, Liver Enzymes, and Risk of Hypertension. Hypertension. 2005;46;1186-1193.

[2] Baker, S.L.. C-Reactive Protein Test for Heart Disease Found Useless. Natural News, Aug. 4, 2009.

[3] CRP Liver Protein Induces Hypertension. Medical News Today ( ). Feb. 22, 2007.

[4] Prevalence of Non-alcoholic Fatty Liver Disease Varies by Ethnicity. Medical News Today ( ). Dec. 8, 2004.

[5] Dryden, Jim. Apple or pear shape is not main culprit to heart woes — it's liver fat. Washington University St. Louis School of Medicine, Public Affairs News Release. Dec 3. 2008.

[6] Harrison, Stephen A., et al. Orlistat for overweight subjects with nonalcoholic steatohepatitis: A randomized, prospective trial. Hepatology. 2009: 49(1); 80-86.

[7] Weight loss reverses fatty liver disease. Indo-Asian News Service. Feb 20, 2009.

[8] Exercise Helps Patients With Non-Alcoholic Fatty Liver Disease. Medical News Today ( ). Jul. 3, 2009.

[9] Moderate exercise can reduce fatty livers in diabetics. Indo-Asian News Service. Sep. 20, 2008.

Sunday, August 9, 2009

Weight Loss and Blood Pressure

Not all obese people have high blood pressure, and not all people with high blood pressure are obese. Nonetheless, there is a strong correlation between being overweight and developing hypertension--so much so that "you ought to lose some weight" is often the first thing a doctor says to a patient who has just been diagnosed with high blood pressure.

Of course, since the doctor doesn't expect that the patient will really make an effort to lose any weight, this advice is often uttered while the doctor is busy scribbling out a prescription for hypertension medication. What is ironic about this is that many anti-hypertensive drugs result in weight gain. (Weight gain is very common with beta-blockers. What is rather surprising is that, although diuretics typically result in an immediate drop in wieght owing to water loss, in the slightly longer term many people report ongoing weight gain from diuretics. Your doctor will no doubt scoff at this idea, but it makes good scientific sense given the fact that diuretics result in insulin resistance and many of the manifestations of diabletes.)

One of the puzzles about weight loss and blood pressure, though, is why losing weight tends to reduce blood pressure in the first place. There are many theories. In overweight people the renin-angiotensin-aldosterone hormone system appears to be overactivated--but this merely moves the question back one stage (since we don't know why being overweight would overstimulate the hypertensive hormonal system).

In overweight people, the sympathetic nervous system tends to be overactivated--but once again, this simply replaces one question with another, since we don;t know why extra pounds casue sypathetic overstimulation.

An appealing theory is one that might be called "the plumbing model." According to some calculations, every additional pound of fat requires about a mile of additional capillaries to supply adequate blood to the fat cells. According to this notion, pushing blood through this enlarged network of tiny blood vessels naturally requires a higher blood pressure leaving the heart. (I've been unable to discover what happens to all those miles of capillaries during wiehgt loss. I guess the body has some way of breaking them down--otherwise we'd end up spiderwebbed with miles of unneeded capillaries right under our skin.)

Much current thinking on the topic suggests that obesity doesn't actually cause hypertension; instead, hypertension and obesity have a common underlying cause, Syndrome X (or "Metabolic Syndrome.") In this model, it is insulin resistance, and high circulating levels of insulin, that cause weight gain and also raise blood pressure. According to this theory, taking dietary measures that begin to reverse Syndrome X and normalize insulin and glucose levels will both result in weight loss and in lower blood pressure--but it is not the weight loss that is causing the lowered blood pressure. (In another huge irony, the diets suggested by most doctors for weight loss--low-fat, high-carbohydrate diets--are exactly the diets that make Syndrome X worse, and often drive people from Syndrome X into full-fledged Type II diabetes.)

The newest theory is that the association of high blood pressure with obesity isn't caused by extra body fat per se, but only by extra fat stored in the liver.[1] (This isn't incompatible with the Syndrome-X theory, since fatty liver is associated with Metabolic Syndrome, and some researchers argue that it is one of the key elements.) In the past year, researchers have discovered that fatty livers secrete C-reactive Protein (CRP), a pro-inflammatory hormone, and CRP acts directly on the endothelium of the blood vessels to increase blood pressure.[2] The majority of--but not all--alcoholics and obese people have fatty livers; this could explain why the majority, but not all, alcoholics and obese people have high blood pressure. If correct, this would mean that blood-pressure researchershave been barking up all the wrong trees for several decades now. (CRP is also closely linked with arteriosclerosis and heart disease, and some researchers now believe that it is CRP, not cholesterol, that damages blood vessels. Yes, cholesterol forms the plaques in diseased arteries--but it is the inflammation caused by CRP that pulls cholesterol out of circulation and deposits it in the artery walls.)

[The recent research on fatty liver deserves a post of its own, and will get one soon.]

Whether extra fat causes hypertension, or obesity and hypertension are caused by a common underlying problem, taking steps that cause weight loss also usually cause a lowering of blood pressure. Different studies on the subject yield different results, which is hardly surprising, since some studies involve exercise programs, some caloric restrtiction, others anti-hypertensive drugs, and many of them employ some combination of those three.

There have been a number of "meta-studies" that use statistical analysis to tease out the effects of weght loss alone from the existing studies. The most recent of these, in 2003, established that in general the loss of one pound of body weight lowered both systolic and diastolic blood pressure by about a half point (to be more price, the numbers were 1.05 mm per kilogram systolic, and 0.92 mm per kilogram diastolic, which amounts to 0.48 mm per pound systolic and 0.42 mm per pound diastolic) [3].

A shy half point might not sound like much, but a pound of fat isn't much either. While losing ten pounds "only" knocks blood pressure down by about five points, losing twenty pounds would drop it by nearly ten points, which is as good as the drop achieved by most blood-pressure drugs.

Furthermore, what the median statistics don't show is the variation between studies, and the variation between individuals within any study. In one of the classic studies, when participants lost an average of twenty pounds, the average blood pressure drops were 30.5 mm systolic and 20.8 mm diastolic.[4] That's 1.5 mm per pound systolic and 1.0 mm per pound diastolic--which is triple the systolic drop, and double the diastolic drop, respectively, compared to the average found in the 2003 meta-analysis.

What these numbers mean is that a great many people with hypertension could normalize their blood pressure simply by normalizing their weight. Since obesity contributes to so many other medical problems, the benefits from weight loss go far beyond controlling hypertension.

Studies show that the vast majority of overweight people wish they could lose the fat they are carrying. Unfortunately, studies also show that the weight-loss recommendations given by most doctors result in only modest losses in many cases, and in the majority of cases result in no long-term weight loss at all, or even result in weight gain. The low-fat diet push that began in the 1970s and has been adopted as gospel by the medical establishment has been a dismal failure. Over the last four decades, Americans have dutifully cut down their intake of fat, both in absolute terms and as a percentage of daily calories--and the result has been an epidemic of obesity across the country.

If you have high blood pressure, then, as the doctor says, you probably ought to lose some weight. But you probably shouldn't take your doctor's advice about how to lose it.

[1] Stranges, Saverio, et al. Body Fat Distribution, Liver Enzymes, and Risk of Hypertension.
Hypertension. 2005;46;1186-1193.

[2]. CRP Liver Protein Induces Hypertension. Medical News Today ( ). Feb. 22, 2007.

[3] Neter, Judith E., et al. Influence of Weight Reduction on Blood Pressure: A Meta-Analysis of Random Controlled Trials. Hypertension 2003;42;878-884.

[4] Reisin E, Frohlich. Effects of weight reduction on arterial pressure. J Chronic Dis. 1982;35:887–891.