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You're only as old as your arteries.

"We've known for well over a hundred years that the large arteries, primarily the aorta and the carotid arteries, stiffen as we get older," says Douglas Seals, a professor of integrative physiology at the University of Colorado at Boulder.

"What we're discovering is that this arterial stiffening is a big reason why some of us develop hypertension, heart disease, and strokes."

But not everyone's arteries stiffen at the same rate.

"You would be surprised by how much variation there is, especially as people get older," Seals notes. "While some 80 year olds have the stiffest arteries, others have arteries that are no different from the average 20 year old's."

Here's what scientists are learning about what can slow down, or even prevent, the aging of our arteries.

How Arteries Age

As we age, the aorta, carotids, and other large arteries that keep oxygen-rich blood flowing through our body lose some of their capacity to widen or narrow. They become less compliant.

"With aging, arterial compliance declines and arterial stiffness increases," notes Kevin Davy, a professor in the Department of Human Nutrition, Foods and Exercise at Virginia Tech University in Blacksburg.

Arteries are most supple at about age 30 and then start stiffening. (1) What makes arteries less accommodating as people age?

* Rigid walls. "The two main structural proteins in the large artery wails are collagen and elastin," explains the University of Colorado's Douglas Seals.

Collagen provides the scaffolding that holds the arteries together, and elastin gives the blood vessels the elasticity that they need to manage the flow of blood.

"As people get older, collagen becomes more abundant in artery walls," says Seals. And, over time, strands of collagen tend to bind ("cross link") with other collagen strands. Both combine to make the large arteries more rigid.

And if there is extra glucose (blood sugar) sloshing around, cross-linking speeds up as the glucose binds to the collagen to form advanced glycation end-products, or AGEs. (See "Extending Life," Nutrition Action, Mar. 2009, p. 7.)

Meanwhile, as the years go by, the elastin proteins stretch out and eventually start to rupture. That makes the arteries lose even more flexibility.

* Damaged linings. It's not just the walls of your arteries that make them stiffer as you age. It's also the lining.

"The endothelium is the inner lining of cells in all of the arteries in your body," says Joseph Vita, a professor of medicine and senior staff cardiologist at the Boston University School of Medicine.

"It regulates where blood flows and how much blood flows to the organs as needed, and it maintains the blood in a fluid state so that it doesn't clot."

Endothelial cells produce nitric oxide, a gas that relaxes and dilates blood vessels. An impaired lining produces less nitric oxide, which leads to less flexible arteries. "This decline in endothelial function contributes to the stiffness," says Davy. What causes the decline?

Age, for starters. And all of the other risk factors that are known to lead to coronary heart disease also have been shown to hinder endothelial function.


"This is true no matter whether it's high blood pressure, cigarette smoking, diabetes, high cholesterol, being overweight, or not doing enough exercise," says Vita.

If your endothelium is abnormal, he notes, "it means that the cumulative load of risk factors and lifestyle has led to damage to your arteries, and you may be at risk of going on to develop heart disease or heart failure or a heart attack or stroke."

When an impaired artery lining produces less nitric oxide, it sets in motion a vicious cycle.

Nitric oxide not only relaxes and dilates blood vessels, but also prevents platelets and white blood cells from sticking to blood vessel walls. So less nitric oxide leads to more plaque buildup in artery walls, which means that the lining produces even less nitric oxide, which leads to more plaque buildup in artery walls ...

"The endothelium is a barometer of the health of your blood vessels," says Vita, "because it's one of the first things to go wrong on the path to atherosclerosis, which is the underlying cause of heart attack and the most common form of stroke."

The Consequences

Scientists are learning that stiffening arteries can often be detected--at least in research laboratories--long before any symptoms of disease appear, and that can predict who will develop cardiovascular disease.

"Clearly, many people of middle and advanced age whom we once thought of as healthy actually aren't," says Edward Lakatta, director of the cardiac function section at the National Institute on Aging in Baltimore.

"It is becoming more apparent that changes in the aging circulatory system, even among those who don't have outward symptoms, precede a higher risk of developing cardiovascular diseases," he adds.

"The greater these changes, the greater is the risk for getting these diseases." Among them:

* High blood pressure. "If your arteries are stiff, that means your heart has to work harder to pump the blood out," Vita explains.

"It's part of the process that leads to heart failure, particularly in patients with high blood pressure."

Nine out of ten people will develop high blood pressure if they live long enough, says Lakatta. "Most of this is systolic hypertension that's directly due to arterial stiffening."

(Systolic pressure--the maximum pressure on the arteries when the heart contracts and pushes blood out--is the top number in a blood pressure reading.)

"Systolic high blood pressure was once thought to be a benign event," notes Douglas Seals. "And some primary care physicians didn't even treat it."

Not any more.

"It's now recognized that increased systolic blood pressure with age is really the blood pressure change that's linked most tightly to premature death in adults over 50," says Seals. "Informed physicians know that it needs to be controlled in middle-aged and older adults."

When arteries are stiff, "blood pumped from the heart moves so quickly through them to the extremities that the pulse wave that is generated bounces back to the heart while the heart is still contracting," Seals explains. That adds to the systolic pressure.

"We showed in the Baltimore Longitudinal Study of Aging that by using measurements of arterial stiffness you could predict the development of hypertension," says Lakatta.

He and his colleagues followed a group of 306 men and women who entered the study with normal blood pressure (roughly 115 over 75). A third of the people developed hypertension over the next 12 years. What most distinguished them from the two-thirds who didn't become hypertensive, says Lakatta, was that they had stiffer arteries when they entered the study. (2)


* Heart attacks & strokes. "Arterial stiffness is as powerful a predictor of future cardiovascular disease risk in older adults as LDL cholesterol or any of the major conventional risk factors," says Seals.

A recent meta-analysis pooled the results of 17 international studies that tracked nearly 16,000 healthy men and women for an average of eight years. Those who entered the studies with the stiffest arteries, but without signs of heart disease, were twice as likely to later die from a heart attack or stroke as those who entered the studies with the most supple arteries. (3)

* Cognitive decline. If your arteries can't expand and contract easily, they can't shield your smaller blood vessels from the regular high-pressure bursts of blood that the heart puts out. And that may damage your brain, a recent study suggests.

People who entered the Baltimore Longitudinal Study of Aging cognitively intact but with stiffer arteries were more likely to show declines in verbal learning skills and memory over the next decade than those who started out with less-stiff arteries. (4)

How Can You Tell?

How do you know whether your arteries are stiffening and if your artery walls are in poor shape? You don't. It's not something that can be measured at the doctor's office (though that may change in the not too distant future). Getting direct measurements from artery walls is even a challenge for researchers.

"You certainly can't go in and sample the arterial wall in a study of people," notes Douglas Seals. "It's been done at autopsy, and you can measure some things in the blood that are thought to play an important influence, but it's not the same as having direct access."

So researchers have to rely on indirect measurements.

For arterial stiffness, a patient lies down while electrodes are placed on the skin along two arteries. A device records how fast it takes for a pulse to travel between two points (pulse wave velocity). The greater the velocity, the stiffer the artery. (Since stiff arteries can't expand well, they pinch the blood flow and send it shooting through at a faster speed.)

Endothelial function is typically measured with something called flow-mediated dilation, which uses ultrasound to see how wide an artery opens after being deprived of blood with a cuff that is tightened on the arm.

If people have impaired endothelial function, their arteries won't widen as much during the test.

What You Can Do

"We are finding that the lifestyle factors that cause arterial stiffening and endothelial dysfunction are the same ones that can help slow them down or even prevent them," says Seals.


"Regular aerobic exercise may have the greatest effect on arterial stiffness," says Seals. "If you compare older adults who do regular aerobic exercise with older adults who don't, you see that the exercisers have more-compliant arteries and less stiffening."

"We were the first to show this in 1993 in the Baltimore Longitudinal Study of Aging," adds the National Institute on Aging's Edward Lakatta. "We compared a group of senior male athletes who started running in middle life with men of a similar age who were sedentary."

Using pulse wave velocity, Lakatta and his colleagues found that arterial stiffness in the exercisers--the youngest was 54 years old--was significantly less than arterial stiffness in the sedentary men. In fact, the arteries of the older exercisers were no stiffer than the arteries of sedentary men aged 20 to 44. (5)

A few years later, Seals and his colleagues found the same was true for women. (6) Arteries got stiffer with age in sedentary women, but not in women who were physically active (they exercised an average of six hours a week and competed in running races).

Why does exercise matter?

"Part of what happens during exercise is that as the physical force of blood accelerates through the arteries it causes the endothelial cells to release nitric oxide," Lakatta explains. "That has beneficial effects on the wall that are anti-stiffness, not only then but over the long haul, too."

Can exercise reverse stiffening if you've been sedentary?

Men who begin exercising after being physically inactive can quickly see benefits. "Studies in older males who have stiff large arteries show that daily walking can lead to a 25 percent improvement in arterial stiffening within three months," says Seals.

"It doesn't make your arteries completely young again, but it helps," adds Bo Fernhall, a professor of kinesiology at the University of Illinois at Urbana-Champaign. "However, it's not some thing that you do and then it stays fixed forever if you stop. So you need to keep doing it."

Exercise can also help improve endothelial function in sedentary men.

In a study by Seals and his colleagues, 13 middle-aged and older overweight, sedentary men gradually increased their walking to about 40 minutes a day, five to six days a week. After three months, the men's endothelial function improved by about 30 percent--comparable to that of men their own age who ran regularly. (7)

"It's important to note," says Seals, "that this was achieved with moderate-intensity walking that can be safely performed by most if not all sedentary, healthy older men."

Women may not be as fortunate. "Regular aerobic exercise in the form of brisk walking does not seem to improve endothelial function in postmenopausal women," says Seals.

In a study by Seals and his colleagues published last summer, endothelial function improved by roughly 50 percent in 11 men who walked briskly for about 50 minutes a day, six days a week, for eight weeks. But it didn't change in 15 healthy women aged 55 to 79 who did the same amount of walking. (8)

"That was unexpected," says Seals. But even if his findings are borne out by future studies, he notes, "exercise has so many positive health benefits that these results obviously should not influence exercise recommendations."

What about strength training? Lifting weights can actually increase arterial stiffening. "Nobody knows why," says Seals. "It may be due to the increased blood pressure that occurs temporarily."

Seals recommends combining strength training with aerobic exercise.

"We want all older adults to do resistance exercise because of its profound effects on muscle preservation. But it's important to keep an aerobic component in addition to strength training to maintain arterial flexibility."

Adding aerobics to resistance training works. In a 2006 Japanese study, for example, the arterial compliance of young men who did resistance training for four months declined by 20 percent, while the arterial compliance of those who combined aerobics with resistance training didn't change. (9)


What you eat can also improve arterial compliance.

* Sodium. "The component of the diet with the most evidence right now for slowing arterial stiffening is sodium," says Seals. "Sodium restriction has a very powerful effect on the arteries."

If you cut the typical sodium intake of U.S. adults roughly in half, he adds, "you see very quickly--within a week--a 25 to 30 percent improvement in the stiffness of the arteries."

For example, researchers slashed the sodium intake of 12 men and women in their 60s who had systolic hypertension (they averaged 148 over 84) from 3,100 milligrams a day to 1,300 mg. Carotid artery compliance increased by 27 percent after one week and by 46 percent after two weeks. It remained at that level for the rest of the month-long study. (10)

"We think that with both aerobic exercise and sodium restriction, we're probably affecting the chemicals that control the smooth muscle cells in the middle part of the artery wall," says Seals. Those are the cells that help arteries open or contract as needed.

* Saturated fat. In 1997 Robert Vogel, a professor of medicine at the University of Maryland School of Medicine, and his colleagues fed 20 hospital employees one of two breakfasts on separate days to see what effect, if any, the meals had on their endothelial function.

One breakfast consisted of an Egg McMuffin, a Sausage McMuffin, two hash brown patties, and a non-caffeinated drink from McDonald's. The other, which contained the same number of calories, consisted of Kellogg's Frosted Flakes, skim milk, and orange juice. The fast-food meal contained 14 grams of saturated fat, while the cereal breakfast had no fat.

Endothelial function started dropping quickly after the fatty breakfast. Within three hours, it was only half of what it had been before the meal. Function remained unimpaired in the participants who ate the no-fat breakfast. (11)

"A few hours after a high-fat meal, your artery looks just like the arteries of a person who has heart disease," says Janet Wallace, a professor of kinesiology in the School of Health, Physical Education, and Recreation at Indiana University in Bloomington.

The hours after a meal are called the "postprandial" period. Given how often we eat, most of us spend all of our waking hours--and some of our time sleeping--in a postprandial state.

"The postprandial period is a critical time because you can be setting the environment for the artery to start or continue the atherosclerotic process that leads to heart disease," says Wallace.

All fatty meals are not equal, though.

"Saturated fat and trans fat are the worst for arteries, whereas polyunsaturated fats and monounsaturated fats like those found in olive oil seem to be less damaging or possibly even healthful," says Boston University's Joseph Vita.

The damage appears after one meal, and it's still evident after many meals.

In one study, 40 middle-aged overweight Australian men and women ate four diets with different fat compositions, each for three weeks.

The diets were high in polyunsaturated fat (with added walnuts and a high-poly margarine), monounsaturated fat (with added canola oil and almonds), sugars (with added jam, marmalade, and grapes), or saturated fat (with added butter).

At the end of each diet period, the participants' endothelial function was measured following an overnight fast.

After the volunteers ate the high-saturated-fat diet for three weeks, their endothelial function was 50 percent lower than after they ate the diets high in polyunsaturated fat, monounsaturated fat, or sugars. (12)

* Vegetables. "The first large, well-designed study to show that eating more fruits and vegetables improves endothelial function was published last year," says Michael Widlansky of the Medical College of Wisconsin.

Researchers in the United Kingdom randomly assigned 117 men and women with hypertension (their blood pressure averaged 143 over 83) to include either one, three, or six servings of fruits and vegetables a day in their normal diet for eight weeks. (13)

Serving sizes were modest: a piece of fruit, half a grapefruit, five ounces of fruit juice, three tablespoons of vegetables.

After the two months, those who were told to eat the most fruits and vegetables had the best endothelial function. In fact, function improved by 6 percent for each daily serving of a vegetable or fruit they ate.

Was the improvement due to something in the fruits and vegetables (like potassium)? Or did arteries improve because the more produce the participants ate, the less sodium and saturated fat they tended to consume? It's not clear.

Either way, the researchers concluded that "Just eating one extra portion a day" of fruits and vegetables "has potential benefits."

* Potassium. In the one randomized controlled trial that has been done, 42 men and women with mild-high blood pressure who consumed potassium supplements (2,500 milligrams) every day for four weeks had improved endothelial function and arterial compliance, compared with when they took placebo capsules. (14)

The best source of potassium: fruits and vegetables.

* Fish oil. "The omega-3 fats in fish oil can improve endothelial function," says Kevin Heffernan of the Molecular Cardiology Research Institute at Tufts Medical Center in Boston. "Clinicians treat heart patients with prescription omega-3s to lower their triglycerides, but this also has the effect of boosting arterial compliance."

For example, 24 middle-aged Australian men and women with high cholesterol levels (an average of 255) were given daily capsules containing 3,000 milligrams of DHA or 3,000 mg of EPA. After seven weeks, their arterial compliance improved by 27 percent with DHA and by 36 percent with EPA, compared with 14 similar people who were given placebo capsules. (15)

(You'd have to eat seven ounces of salmon to get 3,000 mg of DHA, and 15 ounces to get 3,000 mg of EPA.)

Fish oil pills have also improved en dothelial function in people with Type 2 diabetes, peripheral artery disease, lupus, and chronic heart failure.


When people gain weight, their arteries become stiffer.

"I consider weight gain and obesity a form of accelerated aging, at least with regard to the blood vessels," says Kevin Davy of Virginia Tech University. "That's because obesity is an exaggeration of the changes that occur with aging."

Davy and his colleagues fed 14 young men with healthy weights a liquid meal replacement that supplied them with an extra 1,000 calories a day. During the 6 1/2 weeks it took for the men to gain an average of 11 pounds, their arterial stiffness increased by 14 percent. (16)

Although a similar study hasn't been done in middle-aged or older people, "I don't think there's any reason to think the results would be different," says Davy.

"There have been some observational studies of subjects with a large range of ages that suggest that weight gain is associated with increases in pulse wave velocity."

And losing weight improves arterial compliance.

"We helped 25 overweight or obese middle-aged and older men and women lose an average of 16 pounds--about 5 to 10 percent of their body weight--in 12 weeks by cutting calories," says Davy. The people didn't increase their exercise, which let Davy and his colleagues measure the effect of just losing weight.

Arteries became significantly less stiff, he says. "The kind of change we saw in this study was equivalent to a 15-year reversal in arterial aging."

The kind of fat you shed may be as important as the amount.

When Davy had healthy young men gain weight, "the increase in arterial stiffening was more closely associated with increases in the men's visceral fat than it was with the total weight they gained."

(Visceral, or intra-abdominal, fat is the kind deep within the abdomen that's packed between the liver, kidneys, and other organs. Subcutaneous fat sits closer to the skin.)

And among the nearly 2,500 70- to 79-year-old participants in the Health, Aging, and Body Composition Study, those with more abdominal visceral fat had stiffer arteries than those with less. And it didn't matter whether they were normal weight, overweight, or obese. (17)

How can you get rid of excess abdominal visceral fat? The same way you get rid of any fat: cut calories and start moving.

What's Next?

Ten years from now, don't be surprised if testing for endothelial function and arterial stiffness is as routine as cholesterol screening.

"We're moving into an era when it will be imperative to find out what your blood vessels are like before clinical disease sets in so that, if necessary, appropriate measures can be taken to keep your cardiovascular system as healthy as possible," says the National Institute on Aging's Edward Lakatta.

The machines to do that testing are available, though they're expensive and the cost of the tests isn't covered by most insurance policies. But even if you could be tested in your doctor's office, it might be a bit premature, at least for endothelial function.

"The biggest missing piece in the picture is that we don't have proof yet that an intervention to specifically improve your endothelial function will also reduce your cardiovascular risk," says Michael Widlansky.

Getting more exercise and cutting salt, saturated fat, and excess weight protect your artery linings and your heart. But drugs may not do both.

"Estrogen and COX-2 inhibitors like Vioxx improve endothelial function, for example," says Widlansky, "but they're not necessarily protective of cardiovascular health."

Not All Fat is Equal

People who have more visceral fat, which lies deep within the abdomen, are more likely to have stiffer arteries.


If your arteries are stiff and their lining is impaired, you could be setting the stage for cardiovascular disease and cognitive decline.

To make your arteries more supple:

* get regular aerobic exercise,

* cut back on sodium and saturated fat,

* eat a diet that's packed with fruits and vegetables,

* eat two servings of seafood a week, and

* exercise and watch calories to lose or avoid gaining excess visceral belly fat.

Each time your heart contracts, it pumps blood into the aorta, the largest artery in the body. The aorta's walls stretch to accommodate the surge, converting it into a steadier stream that flows up toward your neck. There some blood is carried by the carotid arteries to your head and brain, and the rest flows down to the rest of your body.

"You can liken your arteries when you're young to springs," says Michael Widlansky, an assistant professor of cardiovascular medicine at the Medical College of Wisconsin in Milwaukee. "The vessels are compliant. They open readily so blood can push through them pretty easily and there's not a lot of resistance to the flow."

As we get older, though, the springs start to stiffen and our arteries start to lose their ability to expand when they need to. And that can mean an increased risk of high blood pressure, heart attack, stroke, and cognitive decline.

The good news: you can slow down how fast your arteries age.



If a meal that's high in saturated fat can impair your arteries within hours, imagine the havoc that the fattiest restaurant meals can cause.

After our June 2009 "Xtreme Eating" article highlighted some of the nation's highest-calorie restaurant dishes, ABC News decided to see for itself what the meals did to people's arteries.

The network sent Yunji de Nies, a young reporter (at left), and Jon Garcia, her producer, to Robert Vogel's lab at the University of Maryland Medical Center in Baltimore, where they had their blood vessels tested both before and after eating some of the restaurant dishes we featured.

The two intrepid journalists each ate a three-course lunch: a deep-fried macaroni and cheese appetizer from The Cheesecake Factory, an Applebee's bacon cheeseburger wrapped in a quesadilla, and a giant cookie smothered in ice cream from Uno Chicago Grill. The toll: an astounding 6,190 calories and 187 grams of saturated fat.

Two hours later, lab tests showed the beating their arteries were taking. The producer's blood was discolored with fat, and the young healthy reporter's endothelial function was impaired enough that you could actually hear the difference as sensors picked up her narrowed arteries' struggle to keep blood flowing.

"One meal can affect the health of your arteries," Vogel told the journalists.

To view the ABC News segment, go to: what-exactly-does-a-6190-calorie-lunch-do-to-your-body.html.



Maybe you've seen Louis Ignarro in a Hugh Downs-hosted infomercial on TV or in ads on the Internet, boasting that he has "discovered a 'miracle molecule' that could make bypass surgery, angioplasty and blood pressure drugs obsolete."

The molecule? The amino acid arginine.

The endothelial cells that line the inside of blood vessels convert arginine into nitric oxide. And nitric oxide helps open up arteries and prevents platelets from clotting.

Ignarro, a professor of pharmacology at the UCLA School of Medicine who shared a 1998 Nobel Prize for the discovery of nitric oxide's role in keeping arteries healthy, believes that if people consumed more arginine (which he did not discover, by the way), their blood vessels would make more nitric oxide. That, he contends, would mean that fewer people would get heart disease or high blood pressure.

Arginine is found naturally in most protein foods. Americans typically get 3 to 6 grams a day from their diets. That's not enough, says Ignarro, who recommends an additional 4 to 6 grams a day from pills. (Ignarro teamed up with Herbalife to develop an arginine-containing supplement called Niteworks. He sits on the multi-level marketing firm's Nutrition Advisory Board.)

Others aren't convinced that arginine is miraculous.

"Arginine supplements do not do anything for healthy people with good endothelial function," says Kevin Heffernan of the Molecular Cardiology Research Institute at Tufts Medical Center.

And arginine supplements may not help--and in fact may harm-people with impaired arteries.

When researchers at the Boston University School of Medicine gave 9 grams a day of arginine pills to 28 patients with coronary artery disease for four days, endothelial function didn't improve. It was no better than in patients who got placebo pills. (1)

In another study, 9 grams of arginine every day for six months didn't improve endothelial function or arterial stiffening in 153 men and women who had suffered a heart attack. (2) But six of the arginine takers died during the trial or shortly afterward, while none of the placebo takers did, according to the researchers at the Johns Hopkins Medical Institutions in Baltimore.

"The long-term safety and efficacy of arginine remains ill-examined," says Heffernan. "Arginine cannot be recommended as a general vascular panacea for all aging persons at this time."

(1) Vasc. Med. 14: 239, 2009.

(2) JAMA 295: 58, 2006.

(1) Angiology 61: 37, 2010.

(2) J. Am. Coll. Cardiol. 51: 1377, 2008.

(3) J. Am. Coll. Cardiol. 55: 1318, 2010.

(4) Hypertension 51: 99, 2008.

(5) Circulation 88 (4 Pt 1): 1456, 1993.

(6) Arterioscler. Thromb. Vasc. Biol. 18: 127, 1998.

(7) Circulation 102: 1351, 2000.

(8) Clin. Sci. (Lond.) July 19, 2010. [Epub ahead of print]

(9) J. Hypertens. 24: 1753, 2006.

(10) Hypertension 44: 35, 2004.

(11) JAMA 278: 1682, 1997.

(12) Arterioscler Thromb. Vasc. Biol. 25: 1274, 2005.

(13) Circulation 119: 2153, 2009.

(14) Hypertension 55: 681, 2010.

(15) Am. J. Clin. Nutr. 76: 326, 2002.

(16) Hypertension 51: 1519, 2008.

(17) Hypertension 38: 429, 2001.
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Title Annotation:KEEP IT SUPPLE
Author:Schardt, David
Publication:Nutrition Action Healthletter
Article Type:Cover story
Geographic Code:1USA
Date:Oct 1, 2010
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