Wednesday, December 26, 2007

How extra pounds boost your risk

Why worry roughly speaking XXL size pants? According to a 2006 survey by the American Cancer Society, 83 percent of Americans know that extra flab boosts their probability of a heart attack and 57 percent know that obesity ups their risk of diabetes. Yet with the sole purpose 17 percent know that a growing girth could make them more prone to cancer.


"Five years ago, I would enjoy understood that," say the cancer society's Eugenia Calle. But today, the public's failure to see the nouns is even more out of sync with the science.


"I'm in recent times astounded by how much new information is coming out on heaviness and cancer," says Calle. "I can by a hair`s breadth keep up."


Here's the hottest.


Cancers of the breast, colon, esophagus, kidney, uterus. In 2002, the International Agency for Research on Cancer concluded that people who are overweight or obese hold a higher risk of adjectives five. Now there's evidence for more.


"I would add on gallbladder, liver, pancreas, and advanced prostate cancers to the account," says Eugenia Calle, an expert on cancer and flabbiness at the American Cancer Society. Extra pounds account for an estimated 20 percent of adjectives cancer deaths within the United States. And the percentage is growing ... because Americans are growing.


"We're seeing cancers in a minute linked to tubbiness that we haven't seen surrounded by the past," say Susan Taylor Mayne of Yale University. "And that's scary because of the lofty prevalence of overweight and obesity."


Our expanding national waistline could reverse some of the progress that we've made against cancer, she add.


"Rates of cancer mortality have be declining because of gain in tobacco control," say Mayne. "But we can lose that headway if we lose the war on heaviness."


Why are researchers seeing a stronger link between flabbiness and cancer than in times gone by? "We may not have picked up a contact 20 years ago because fewer race were overweight 20 years ago," say Yale's Susan Taylor Mayne.


For example, experts estimate that in the United States, excess solidity explains roughly:


* half of adjectives uterine and esophageal cancer,


* a fifth (in women) to a third (in men) of all colorectal cancer,


* a third of adjectives kidney cancer,


* a quarter of all pancreatic cancer, and


* more than a fifth of adjectives postmenopausal breast cancer. (1)


But in Europe, where on earth obesity rates are lower--like ours be 20 years ago--excess weight explains a lower percentage of most cancer. (1)


"The list of cancer related to obesity is growing," say Mayne. "It's alarming."


How much of a spare tire do you need beforehand your risk climbs? It depends. For some cancers, risk starts to rise even until that time you cross the line that define "overweight." (See "Extra Weight & Cancer Risk," pp. 4 & 5.)


"With breast, colon, and endometrial cancer, you can see an increase in risk at the high stop of the normal-weight range compared to the low finale," says the American Cancer Society's Eugenia Calle. "And consequently the risk increases in an almost linear fashion from the drastically lean to the very unwieldy."


That's partly because the "normal-weight" scale is quite colossal. "Two people of impossible to tell apart height could be 30 to 50 pounds apart and still be majority weight," she explains.


For some cancer, only heavier relatives appear to be at risk. "For example, it seems resembling there's no increase in the risk of pancreatic cancer until you seize very lashing," says Calle. But that may simply echo incomplete data.


"Most studies own used Body Mass Index, or BMI, as a measure of podginess, and that's not the best measure for adjectives cancers," she say. "For example, now we're looking at waist circumference and pancreatic cancer and finding a stronger effect."


The lengthening schedule of cancers allied to obesity, say Mayne, suggests that "it may be a systemic effect." That's because fat tissue isn't freshly dormant storage space. It's an active organ, releasing and acceptance signals from other organs.


So far, three main theories explain how those signals may comfort turn healthy cell into tumors.


I. The Insulin Pathway


Insulin is the hormone that allows blood sugar to enter cells, where on earth it is either burned for vivacity or stored as fat.


But if you enjoy too many overstuffed hefty cells, they can become resistant to insulin. It's as though the cell were trying to shut the door that would permit in even more sugar.


With insulin losing its punch, the pancreas ramp up its output of the hormone.


"If you have more or bigger flabby cells on the bus, the pancreas is forced to produce more insulin," says Michael Leitzmann, an epidemiologist at the National Cancer Institute.


High insulin level are especially likely if you enjoy what experts call "centralized obesity" (see "Waist Not ..." p. 7).


"These are people who hold an apple-shaped body with a big waist instead of the pear-shaped associates with big hips," explains Karen Margolis of the University of Minnesota and HealthPartners Research Foundation in Minneapolis.


It's clear that insulin resistance increases the risk of diabetes and heart disease. Now cancer may fix together those ranks. "It's likely that the insulin pathway and insulin resistance are high-status for cancers of the colon, liver, pancreas, and kidney," say Calle.


How? Insulin prompts the body to make insulin-like growth factor 1 (IGF-1). In tryout tubes, both insulin and IGF-1 make cell proliferate. (1)


"Insulin itself stimulates growth, so it could act directly on cancer cell," says researcher Edward Giovannucci of the Harvard School of Public Health. "And insulin sensitizes the cell to IGF-1."


It's not that overweight people necessarily hold more IGF-1. Rather, "insulin decreases IGF-1 binding protein, so in that's more free IGF-1 in the blood," he explains.


Here's what researchers know just about cancers associated to the insulin pathway.


* Liver. "Peripheral fat contained by the thighs and hips--where a lot of women fetch their fat--is not that metabolically active," say Calle.


On the other hand, the "visceral" flab around the waist is constantly sending out signals that promote inflammation or growth elsewhere in the body.


(Inflammation, which is often outwardly invisible, is the immune system's attempt to scrap off and repair the interrupt caused by germs, irritants, or other insults.)


"We're not chitchat about the subcutaneous band of fat between the skin and muscles," add Calle. "We're talking around the fat aft the muscle wall that surrounds the organs." (See "Waist Not ..." p. 7.)


"People don't realize that once you get beyond a spot on level of flier posity, fat starts to infiltrate muscle and organs similar to the liver."


In the past, excess alcohol accounted for most fatty livers. "But the most adjectives cause of out of the ordinary liver tests contained by the United States now is non-alcoholic fatty liver disease," say Calle.


A fatty liver starts out benign, but it can lead to cell injury, scarring, and inflammation. "It can progress from fatty liver to hepatitis to cirrhosis to liver cancer," say Calle.


So far, studies suggest that the obese have anywhere from 1 1/2 to 4 times the risk of liver cancer. (1,2) But the disease is still in danger of extinction in the United States, so it's harder to bring a precise risk estimate.


* Colon. Colon cancer isn't rare. It kill more non-smokers than any other cancer.


In the National Institutes of Health-AARP Diet and Health Study, which tracked more than 300,000 men and 200,000 women for five years, the heaviest men had twice the risk of colon cancer, while the heaviest women have a 50 percent increase in risk. (3) But that doesn't mean that everyone else is within the clear.


[GRAPHIC OMITTED]


"The risk increases even for people who are mildly overweight, which isn't soothing for people who hold a couple of extra pounds," explains the National Cancer Institute's Michael Leitzmann.


Why does obesity seem to be to matter more contained by men than women? Fat around your waist is the culprit, and men are more likely to gain mass there.


Giovannucci and colleagues found that men near a waist measuring at lowest 43 inches had a 2 1/2 times greater risk of colon cancer than men beside a waist smaller than 35 inches. (4) And a big belly often go hand contained by hand near excess insulin.


"In human and animal studies, insulin levels are correlated beside risk," says Giovannucci. For example, the complex a rat's insulin level, the more its colon cell proliferate. (5)


"The data linking insulin to risk is stronger for colon than for any other cancer," say Giovannucci.


* Pancreas. Pancreatic cancer is deadly. Only one within five patients is alive one year after diagnosis, and only one surrounded by 25 survives five years. The only set risk factors are cigarette smoking, diabetes, and size.


"In the past six years, a huge number of studies using prospective facts have shown a extremely strong association between obesity and pancreatic cancer," say researcher Dominique Michaud of the Harvard School of Public Health.


In most studies, being obese doubles the risk. (6,7) "For population who are overweight, the link isn't as strong as it is for other cancer," says Michaud. "It shows up more for the obese."


A few studies, resembling the European Prospective Investigation into Cancer and Nutrition (EPIC), which tracked more than 430,000 men and women for six years, found a stronger link next to waist size than with heaviness per se. (8) But other than EPIC, "near's very little background on waist circumference," Michaud notes.


It's still not clear how excess cooking oil leads to pancreatic tumors. "It's probably a consequence of sustained difficult levels of and insulin in the blood," suggests Michaud.


Inflammation may also play a role, she add, "because people who are obese own higher level of inflammation."


Again, it's the visceral fat cell deep surrounded by the belly that appear to be at fault. "Those flabby cells are different," Michaud explains. "They're actively cause trouble."


* Kidney. Although kidney cancer accounts for only going on for 2 percent of cancer deaths, the incidence is rising in the United States and worldwide. Smoking, diabetes, big blood pressure, and obesity adjectives seem to incline the risk, but it's not clear if a large waist matter more than a large number on the bathroom level.


In many studies, excess overweight anywhere in the body raise the risk. (9) But in the Women's Health Initiative, which tracked going on for 140,000 U.S. women for nearly eight years, those with the largest waists (for a given hip size) have double the risk. (10)


"Central obesity be the strongest risk factor in these women," say the University of Minnesota's Karen Margolis, who co-authored the study.


What's more, U.S. women who had lost or gain over 10 pounds more than 10 times during their lifetime had a 2 1/2 times greater risk of kidney cancer than those beside stable weights.


"It appears that weight cycling has a pretty strong relationship next to kidney cancer, particularly at the extreme," say Margolis. "But we don't know why."


II. The Estrogen Pathway


If you're overweight but don't carry the extra pounds surrounded by your waist, are you off the hook?


No. Fat--whether it's around your hips, thighs, waist, or wherever--produces steroid hormones resembling estrogen.


"Another main passageway that obesity can lift the risk of cancer is through the estrogen pathway," says the American Cancer Society's Eugenia Calle.


In premenopausal women, estrogen comes largely from the ovaries. "After the ovaries stop functioning, the primary source of estrogen production is adipose [fat] tissue," Calle explains. "And estrogen is associated beside endometrial and breast cancer."


As with IGF-1, size depresses levels of binding proteins.


"There's not as much sex-hormone-binding globulin level in the circulation, so smaller number estrogen is bound" and free estrogen goes up, say Calle. And that increases risk. Some specifics:


* Breast. The risk of postmenopausal breast cancer rises by 30 percent in overweight women and SO percent in obese women. (11) For years, researchers couldn't detect the link because they didn't separate women who purloin estrogen pills from those who don't.


"Weight is not related to breast cancer in postmenopausal women who help yourself to hormones," says Calle. That's because the pills lift estrogen levels--and the risk of cancer--whether the women are skinny or plump.


"The sharp decline in the number of women taking postmenopausal hormones means that shipment matters to an increasing segment of the population," she add.


More than other cancers, postmenopausal breast cancer is related to how much bulk you gain as an adult. (12) "That's surrounded by part because portliness may lower the risk of breast cancer in pre-menopausal women," say Calle.


Why? Obesity seems to impair their means to ovulate. "So the woman with the top risk was run of the mill weight and have regular periods when she be young and become obese when she got elder," Calle explains.


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In a study of 44,000 postmenopausal women who weren't taking estrogen, those who gained 21 to 40 pounds after age 18 have a 68 percent higher risk of breast cancer that spread beyond the breast than those who gain 20 pounds or less. The risk be nearly double for those who gained 41 to 60 pounds and triple for those who gain more than 60 pounds. (13)


"Excess adiposity is an important contributor to breast cancer risk surrounded by postmenopausal women, especially for tumors that are most likely to spread," say Calle.


* Uterus. Cancer of the endometrium (the lining of the uterus) is twice as expected in overweight women and 3 1/2 times more plausible in obese than within normal-weight women. (1)


"That was the first cancer we reputable as related to obesity," say Calle. And it's clear why excess fat threatens the uterus. "We know that endometrial cancer is associated next to estrogen that's unopposed by progestin."


Decades ago, researchers found that women who took estrogen pills had a complex risk of uterine cancer, but the risk disappeared in women who took estrogen combined with progestin.


Recently, researchers enjoy detected a higher risk among women near central heaviness. In a study of 223,000 European women, the risk of uterine cancer in those with at lowest possible a 35-inch waist was 76 percent difficult than in those next to a waist smaller than 32 inches. (14)


"Once you get to some height of obesity, you're going to enjoy a certain amount of important adiposity no matter where on earth you carry your weightiness," says Calle.


III. Local Impact


For some cancer, obesity seem to boost risk because it leads to problems contained by nearby tissues (rather than by altering circulating hormones). For example:


* Esophagus. Two distinct cancer show up in the esophagus. With a five-year survival rate of 16 percent, both are deep.


But there are differences. The incidence of squamous cell carcinoma (which is adjectives in alcoholics, who are recurrently underweight) is flat or dropping, while rates of adenocarcinoma (which is common contained by the overweight) are on the upswing.


"The incidence of adenocarcinoma is going up more in men than in women and no one know why," says Yale's Susan Taylor Mayne. Obesity may own more impact in men, she suggests.


At first, researchers thought that a wider girth lead to esophageal cancer because it caused sour from the stomach to flow back into the esophagus, cause inflammation.


"Obesity may be acting to promote cancer in part via bitter reflux, but it may also be acting independently," says Mayne.


"In our study, when we controlled for reflux, we still found a strong effect of tubbiness, so risk is not just driven through reflux." (15)


* Gallbladder. The gallbladder is a pear-shaped organ below the liver that collects and stores bile (a fluid made by the liver to digest fat). In in the region of a quarter of all cases, gallbladder cancer is found impulsive (usually when the organ is removed for other reasons), and the five-year survival rate is 80 percent.


But more often, the tumor is discovered too belatedly to be surgically removed. If that happens, solely 5 percent of patients live for two years.


While gallbladder cancer is rare, excess counterbalance accounts for more than a third of all cases surrounded by the United States. How?


"Obesity is associated with gallbladder stones," explains Calle. "The stones provide a local inflammatory environment," which sets the stage for cancer.


Uncertain Pathways


Researchers are still in the gloom about how plumpness may raise the risk of some cancer. For example:


* Prostate. Prostate cancer strikes one out of six men sometime in their lifetime. But solely one in 34 dies of the disease.


Researchers saw no consistent knit with substance until they separated men with local, smaller amount aggressive cancers from those beside more aggressive or fatal cancer. (16)


"Obesity is associated only near the more aggressive prostate cancers," say Harvard's Edward Giovannucci. "So it's possible that obesity doesn't impose prostate cancer, but makes prostate cancer more probable to progress."


For example, when researchers followed more than 285,000 men from the National Institutes of Health-AARP Diet and Health Study for five years, the risk of dying of prostate cancer was 25 percent superior in those who be overweight than in those who be normal counterweight. And the risk was twice as illustrious in the most obese men. (17)


Among the possible explanations: "Obesity may increase the blood supply to the tumor or increased growth factor like insulin could make happen it to progress," suggests Giovannucci. "Or it's possible that not all prostate cancer are alike."


In other words, aggressive cancers may hold a different cause than those that don't spread.


"It looks approaching there are at least possible two distinct types of prostate cancer," explains the National Cancer Institute's Michael Leitzmann.


"We can separate them according to the grade--how abnormal the cancer cell are--and according to the stage--whether they've spread beyond the prostate gland or not."


And obesity may promote one and only the aggressive (higher grade, superior stage) cancers. In reality, excess fat may protect against localized prostate cancers-those "you'll die next to, not from," says Leitzmann.


Why? Higher level of insulin, free IGF-1, and leptin (a hormone that's secreted by fat cells) are potential culprits. (7) So is testosterone.


"Heavy men own lower testosterone levels," explains Leitzmann. "We know that testosterone lead to the start of prostate cancer."


But testosterone also helps verbs the structure and function of the prostate cells, say Leitzmann. "So the cells are more possible to go awry if testosterone level are low."


That's speculative, he adds. "But it's possible that illustrious testosterone levels clear you more likely to carry the disease, but low testosterone levels engineer the disease worse once you get it."


(1) Nature Reviews 4: 579, 2004.


(2) N. Engl. J. Med. 348: 1625, 2003.


(3) Am. J. Epidemiol. 166: 36, 2007.


(4) Ann. Intern. Med. 122: 327, 1995.


(5) Endocrinol. 147: 1830, 2006.


(6) Cancer Epidemiol. Biomarkers Prev. 14: 459, 2005.


(7) Gastroenterol. 132: 2208, 2007.


(8) Cancer Epidemiol. Biomarkers Prev. 15: 879, 2006.


(9) Int. J. Cancer 118: 728, 2006.


(10) Am. J. Epidemiol. DOI: 10.1093/aje/kwm137.


(11) Am. J. Epidemiol. 152: 514, 2000.


(12) JAMA 296: 193, 2006.


(13) Cancer 107: 12, 2006.


(14) Cancer Causes Control 18: 399, 2007.


(15) J. Natl. Cancer Inst. 95: 1404, 2003.


(16) Cancer Epidemiol. Biomarkers Prev. 15: 1977, 2006


(17) Cancer 109: 675, 2007.


Waist Not ...


Extra lining anywhere seems to boost your risk of cancer of the breast, uterus, esophagus, gallbladder, and prostate. But other cancers--colon, liver, pancreatic, and kidney-are more closely linked to the visceral butter that's underneath your stomach muscles (see illustration).


[ILLUSTRATION OMITTED]


Unlike subcutaneous or retroperitoneal fat, which is smaller number active, visceral butter is busy pumping out a slew of hormones--like leptin, adiponectin, and IGF (insulin-like growth factor)--that cause trouble.


"That's why intermediate obesity is related to diabetes, heart disease, and cancer," say Dominique Michaud of the Harvard School of Public Health. "We wouldn't have adjectives those complications if overweight people be just carrying extra counterbalance around."


How do you know how much of your fat is visceral?


You can't speak about without a CT-scan, MRI, or other imaging technique. But your waist circumference is a upright proxy, because a big belly usually means rich deposits of both visceral and subcutaneous butter.


(When studies measure waist circumference or waist-to-hip ratio, they report on participant' "central obesity" or "abdominal obesity," fairly than visceral fat.)


Women beside a waist bigger than 35 inches and men with a waist bigger than 40 inches hold a higher risk of heart disease and diabetes. But for cancer, the cutoffs are smaller number clear.


The question is: how can you hold on to fat away from your innards?


On one paw, genes seem to opt whether you end up next to an apple or pear shape--with more weight around your middle or around your hips.


Hormones also play a role, since women tend to turn up in waist size after menopause. But that doesn't expect you're helpless.


Here's what we know so far:


* Don't fall for gimmick. Despite what you see in ad for weight-loss pills, potions, and gadgets, here is no way to target belly excess weight when you're losing weight. Sit-ups, crunches, and other exercises can strengthen abdominal muscles, but they don't liquefy belly fat any more than other curvy deposits.


* Count calories in and out. Cutting calories coming in or boosting calories going out have the same impact. In a six-month study of 35 overweight men and women, in attendance was no difference surrounded by visceral fat loss among nation who cut calories by 25 percent or who cut calories by 12.5 percent and burned 12.5 percent more calories than usual. (1) Both lost about 10 percent of their freight and 27 percent of their visceral fat. Of course, exercise can also backing lower the risk of heart disease, diabetes, and cancer, even if you don't lose weight.


* Cut calorie-dense, nutrient-poor foods. It's easier to slim down if you riddle up on vegetables, fruit, and other foods that aren't calorie-dense. Limit calorie-dense fatty foods (especially if they're high within saturated and trans fats) and carbohydrates (especially sweets, white potatoes, and breads, cereal, rice, and pasta made with sophisticated flour). And don't drink your calories, whether it's alcohol, soda, or juice.


* Don't lately sit there. The more time you spend on the couch, within the car, or at the computer, the more hefty you invite into your abdominal home.


In a study of 175 overweight, sedentary men and women, one group walked 12 miles a week (which took nearly 3 hours), a second group jogged 12 miles a week (2 hours), a third group jog 20 miles a week (3 hours), and a fourth group stayed inactive. (2)


After six months, the 20-mile joggers have lost 7 percent of their visceral fat, while the 12-mile walker and 12-mile joggers--who burned roughly the same calories--had lost no visceral solid. But the real surprise be the control group. In just six months of inertia, their visceral fat jump 9 percent (see graph). And in a recent rat study, apathy made rats grow more fat cell. (3)


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The bottom line: What matter is how many calories you burn when you exercise--whether it take you 1 hour, 2 hours, or whatever--not whether it's high intensity (like jogging) or moderate intensity (like walking). But what matter most is that you get sour your derriere.


So, for now, put away less and move more--all easier said than done, obviously.


How to measure your waist circumference:


1. Place a cassette measure around your unclothed abdomen purely above your hip bone.


2. Be sure that the tape is snug, but does not compress your skin, and is parallel to the floor.


3. Relax, exhale, and benchmark.


(1.) J . Clin. EndocrinoL Metab. 92: 865, 2007.


(2.) J . Appl. Physiol. 99: 1613, 2005.


(3.) J . Appl. Physiol. 102: 1341, 2007.


Extra Weight & Cancer Risk (Women)


[ILLUSTRATION OMITTED]


As a woman's BMI rises above the normal collection (18.5 to 24.9), her risk of dying of several cancers also rises. For example, the risk of dying of uterine cancer is 50 percent greater for women who are overweight (a BMI between 25.0 and 29.9) than for women who are normal substance. For the most obese women (a BMI of 40 or higher), the risk is roughly six times higher. The line for gallbladder cancer stops rash because there be too few deaths among the most obese women within this study to separate those with a BMI of 35 or greater. (To find your BMI, see "How Fat is Fat?" p. 6.)


Source: Data from New EngL J. Meal. 348: 1625, 2003.


Extra Weight & Cancer Risk (Men)


[ILLUSTRATION OMITTED]


As a man's BMI rises above the average range (18.5 to 24.9), his risk of dying of several cancer also rises. For example, the risk of dying of colorectal cancer is 20 percent higher for men who are overweight (a BMI between 25.0 and 29.9) than for men who are conventional weight. For the most obese men (a BMI of 35 or higher), the risk is almost double (84 percent higher). This study have no separate data for men next to BMIs of 40 or greater. (To find your BMI, see "How Fat is Fat?" p. 6.)


Source: Data from New EngL J. Med. 348: 1625, 2003.



How Fat is Fat?

The numbers apply to both men and women, but they're
Not foolproof. Very muscular people may hold a high
BMI lacking health risks. And frail or elder people
may be weak even though they have a low BMI.

(To figure your BMI: Find your height, consequently look across
that row. Your BMI is at the top of the column that comes
closes to your weight.)

BODY MASS INDEX (BMI)

NORMAL OVERWEIGHT

HEIGHT 19 20 21 22 23 24 25 26 27 28

WEIGHT (pounds)

4'10" 91 96 100 105 110 115 119 124 129 134
4'11" 94 99 104 109 114 119 124 128 133 138
5'0" 97 102 107 112 118 123 128 133 138 143
5'1" 100 106 111 116 122 127 132 137 143 148
5'2" 104 109 115 120 126 131 136 142 147 153
5'3" 107 113 118 124 130 135 141 146 152 158
5'4" 110 116 122 128 134 140 145 151 157 163
5'5" 114 120 126 132 138 144 150 156 162 168
5'6" 118 124 130 136 142 148 155 161 167 173
5'7" 121 127 134 140 146 153 159 166 172 178
5'8" 125 131 138 144 151 158 164 171 177 184
5'9" 128 135 142 149 155 162 169 176 182 189
5'10" 132 139 146 153 160 167 174 181 188 195
5'11" 136 143 150 157 165 172 179 186 193 200
6'0" 140 147 154 162 169 177 184 191 199 206
6'1" 144 151 159 166 174 182 189 197 204 212
6'2" 148 155 163 171 179 186 194 202 210 218
6'3" 152 160 168 176 184 192 200 208 216 224
6'4" 156 164 172 180 189 197 205 213 221 230

NORMAL OVERWEIGHT

HEIGHT 29 30 35 40

WEIGHT (pounds)

4'10" 138 143 167 191
4'11" 143 148 173 198
5'0" 148 153 179 204
5'1" 153 158 185 211
5'2" 158 164 191 218
5'3" 163 169 197 225
5'4" 169 174 204 232
5'5" 174 180 210 240
5'6" 179 186 216 247
5'7" 185 191 223 255
5'8" 190 197 230 262
5'9" 196 203 236 270
5'10" 202 207 243 278
5'11" 208 215 250 286
6'0" 213 221 258 294
6'1" 219 227 265 302
6'2" 225 233 272 311
6'3" 232 240 279 319
6'4" 238 246 287 328

OBESE

Source: National Heart, Lung, and Blood Institute.

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