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Cholesterol – What the New Numbers Mean

The waiter at the famous restaurant on Limone’s waterfront approaches the table of portatori, bearing armloads of plates like polenta with mushrooms, shrimp salads, and also pastas in various disguises. The bottles of white wine are pushed aside to make room for the red.

“I eat and drink so much now I am becoming as wide as a boat” says Lusi Gerald, who by her own admission likes to sleep until noon. “If I exercised and did not smoke or drink, I would be a super woman” then She lights her second cigarette of the meal. “I don’t want to be a super woman”.

Limone’s portatori credit their good health to more than just the protein, as they call their fortuitous mutation. “It is the olive oil” insists Peter Gerald, referring to Limone’s locally produced virgin olive oil. He is not so far off.

In 1988 experts with the United State National Cholesterol Education Program advised healthy adults over the age of 19 to get a cholesterol test every five years. But it has become clear that this basic test doesn’t do a good enough job of predicting who is going to get heart disease. So in 1993 the recommendation changed : Everyone should be tested for total cholesterol and for HDL (so called good cholesterol). Unfortunately HDL tests are not always accurate, in part because the techniques some laboratories use are unreliable. You can always ask your doctor whether you can trust HDL results from your laboratory.

Together, total cholesterol and HDL tests

give an idea of your levels of low-density lipoprotein, or LDL (so called bad cholesterol) that causes plaque to form in the arteries. LDL is not measured right off the bat, because the test is more difficult (it’s level is calculated using a formula that includes triglycerides, blood fats whose levels rise after meals). And getting your triglyceride levels requires a fast of at least nine hours to ensure they are at their baseline level. If your HDL or total cholesterol levels look bac, you will probably need this more complex LDL test.

Interpreting Your Results

High-density Lipoprotein (HDL)

Under 35 : This is not good. No matter what your total cholesterol score, you should have your blood analyzed for the level of LDL.

Over 35 : Anything between 35 and 60 is considered acceptable. And HDL level above 60 is thought to protect against heart disease, but you are not completely in the clear unless your total cholesterol score checks out as well.

Total Cholesterol

Under 200: So far, so good. As long as your HDL level is at least 35, you can wait as long as 5 years before repeating the test.

200 to 239 : Borderline. Repeat the test within 2 years.

240 and over : High. You need to have your blood analyzed for LDL levels

Low-density Lipoprotein (LDL)

Under 130: Great. You do not need to be retested for total cholesterol and HDL for 5 years.

130 to 159 : Borderline high. What you should do depends on whether you have other risk factors. If you have no more than one other risk factor, you can wait a year and see what another test says. In the meantime, exercise and cut down on foods high in saturated fat and cholesterol. If you have two or more risk factors, follow the advice for those with high LDL.

160 or above : High. You need a doctor’s exam to determine of your LDL level is due to a treatable medical condition, such as liver or kidney problems. Your doctor will put you on a diet very low in saturated fat and cholesterol, designed to lower LDL. If your levels don’t respond after 6 months, you may be prescribed cholesterol lowering drugs.

AM I AT HIGH RISK ?

You are if you have two or more of the following risk factors. (Subtract a factor if your HDL level is at 60 or above).

  • You have high blood pressure or diabetes
  • You have a family history of premature heart disease (before age 55 in male relatives, age 65 in female relatives)
  • You smoke
  • You are a man over 44 or a woman over 54 (or if a younger woman, you are experiencing premature menopause without estrogen replacement therapy)
  • Your HDL is below 35

Can cholesterol be too low ?

A few years ago many people were confused and worried by research suggesting that low blood cholesterol itself is risky. The studies indicated that when total cholesterol drops below 160, it increases the risk of dying of cerebral hemorrhage – a type of stroke and of certain types of cancer or by accident, murder or suicide. But closer inspection has revealed that low cholesterol is not to blame. Instead there are some medical conditions such as stomach or liver disorders, that lower cholesterol and increase the risk of death. There are some habits that do both as well, such as heavy drinking or smoking. These not only wreak havoc on organs but also increase the risk of accidents and other mis-adventures.

In short, people who have naturally low cholesterol levels should be thrilled, not worried. What’s more, heart patients who get their total cholesterol down to 160 milligrams have fewer heart attacks, require fewer treatments like bypass surgery, and live longer than do patients whose levels remain high.

Predicting the Risk of Heart Disease

The numbers are frightening. Each year 1.5 million Americans have heart attacks, 500.000 of them fatal. The statistics or even scarier for anyone with a family history of heart disease, because if one family member develops heart disease before age 55, other blood relatives like children, brothers, sisters will face a fivefold to tenfold risk of becoming cardiac casualties t

hemselves. In fact, just 3% to 8% of American families account for 40% to 60% of premature coronary deaths.

In the most extreme conditions a single gene can virtually guarantee a person’s destiny. One in a million Americans inherit 2 copies of a flawed gene that causes familial hyper cholesterolemia, for example. This disorder hampers the ability of cells to take cholesterol from the blood, allowing cholesterol levels to soar as high as 1000 mg. Frequently people with severe familial hyper cholesterolemia develop artery blockages by the age of two. Without radical treatment, such as a liver transplant, they usually die in their teens.

By contrast, Helen Boley, a 63 year old Kansas woman, inherited two copies of the rare “Methuselah” gene, which prompts her body to make HDL at three times the normal rate. Boley’s HDL measures about 200 mg (60 mg is average for a woman her age). Several of Boley’s ancestors lived past 100 years, seven of her great grandparents were alive when she was born. Helen Boley could not die of heart disease if she tried.

Of course, genetics doesn’t deal most people as good a hand as Boley’s or as bad as the one held by people with familial hyper cholesterolemia. But there’s usually no way to tell exactly what kind of genetic odds you face when it comes to heart disease.

Instead, doctors trying to predict their patients risk have turned to markers in the blood that can contribute to heart disease. The first push, in the late 1980’s was to get everyone tested for total blood cholesterol, a measurement that primarily reflects of the levels of low density lipoprotein also known as LDL (“bad” cholesterol). There’s good reason to get that number since LDL is the real culprit in clogged arteries but is difficult to measure by itself. Generally, the higher the level of total cholesterol, the greater the heart-disease risk. Someone with a total cholesterol reading of 240, for example is at twice the risk of someone with a reading of 210. But it has become clear in the past few years that these medical horoscopes can be misleading. As many as one in 5 people with scores considered desirable (under 200) eventually have heart attacks. Others with riskier levels are spared. In June 1993 heart experts with the US National Cholesterol Education Program announced a major missing puzzle piece. Everyone over the age of 19, the experts said, should also be tested for HDL, the “good” cholesterol the same stuff that is present in a souped-up form in the Limone villagers.

HDL, it seems is one reason why premenopausal women are comparatively free of heart disease. Their HDL runs about 10 mg higher on average than in men of the same age. (Estrogen therapy, which boosts HDL levels by about 10%, also cuts the risk of heart disease in postmenopausal women by half.) In study after study, HDL levels above 60 mg seem to protect against heart disease.

“Cholesterol is a was”, says John Oram, a cell biologist at the University of Washington in Seattle. “It adds strength to cell membranes, but if cells accumulate too much cholesterol it jams up their membranes. If we did not have some way to take it out, we’d turn into candles”. So if cholesterol is the was gumming up the works, HDL is the dump truck that carts it from the cell to the liver for disposal. The more HDL, the more efficiently the trash is hauled. Researchers have been particularly interested in how the portatori’s mutated version works, because it apparently binds and releases cholesterol quickly, perhaps as much as ten times faster than normal, like a tiny fleet of dump trucks tearing through the blood stream in hyperdrive.

It’s been suspected that HDL helps in another way as well, by making blood platelets less sticky. That leaves platelets less likely to form clots that can get stuck in narrowed arteries, choking off the blood supply and causing a heart attack. Investigation of the portatori appears to confirm this second role for HDL. In the test tube Apo A-1 Milano has shown remarkable anti-clotting properties.

A Swedish drug firm is exploring ways to turn the hyperactive Apo A-1 Milano into a heart medicine. Kabi Pharmaceutics is doing animal tests on an inject-able drug derived from the protein to see if it can keep arteries from reclogging after they’ve been cleared by balloon angioplasty. Eventually the work may lead to drugs that can scour out blocked arteries without the need for surgery at all.

Experts agree that measuring both total cholesterol and HDL offers the best chance of evaluating someone’s heart disease risk. Other blood markers may join the list in the future, since some people at high risk will still be missed by these tests. One leading candidate is something called small dense LDL. This type of cholesterol is the best signal of syndrome X, a disorder that increases the risk of high blood pressure, heart disease and diabetes. Syndrome X may affect as many as one in 4 Americans.

For now, though scientists trying to learn how to predict cardiovascular disease gather important information from groups like the Limone folk. Of course, it won’t do much good to identify people heading for heart attacks if they can’t do anything about it. Which raises two crucial questions, Can a healthful lifestyle override dangerous genes ? And can a lifetime of bad habits produce heart disease in someone with no particular predisposition to it ?

Golden Gene Discovered In Italian Small Town

It was an act of God, the locals say that wedged the Italian village of Limone between a range of steep, rocky mountains and the deep waters of Lake Garda, protecting its lemon and olive groves from harsh weather and its villagers from marauding invaders. But it was an act of nature: a genetic quirk – that eventually put the village on the map.

For hundred years, the villager’s stark isolation forced them to marry within a small circle of families. So in 1700 when Cristoforo Pomaroli and Rosa Giovanelli had a son with a genetic mutation that did strange things to the cholesterol in his blood, the gene slowly insinuated itself into the major bloodlines of the village. It was to remain undetected for nearly 200 years.

Not until 1931, when 79 tunnels were blasted into the surrounding mountains to create a road, did the Limone villagers tart to make regular contact with the larger world. Nowadays a million visitors come each year to enjoy the areas beaches, mountain trails and ancient stone buildings ablaze with oleander blossoms. Scores of scientists journey here, too. For them the biggest attraction can be found sitting around a lunch table at a Limone restaurant : descendants of that baby whose gene, it seems, makes it nearly impossible for them to develop coronary heart disease.

There is Amelio Segala, a leather goods seller, who says almost

everyone in his family lives to 90 years of age. Theres is Bruna Girardi a housewife, and her brother Davide a flower vendor, whose family is equally long lived. They received their priceless inheritance from their father. There is Maria Bernardi a hotel clerk, who counts her family blessed; she passed the gene on to her 13 year old son, Dante. They are just a few of the 46 villagers who have come to be called the portaiori : the carriers.

The Gene’s Discovery

The gene might never have been discovered if it had not been for Valerio Dagnoli, a railroad man in Milan who in 1975 sought relief for an irritable colon. Routine testing drew the doctor’s attention

away from Dagnoli’s intestines, though. A blood test showed high levels of triglycerides, a type of blood fat. Triglyceride levels over 500 milligrams can indicate an increased risk of heart disease and Dagnoli’s were as high as 600 mg. Worse, medicine only made the triglyceride levels rise higher. The doctor had never seen anything like it and he referred Dagnoli to the Lipid Center in Milan. There Dagnoli came to the attention of cholesterol specialist Cesare Sirtori.

Sirtori, now a clinical pharmacologist at the University of Milan, found that the patient’s triglyceride levels were just one of the several battling blood test scores. Dagnoli’s total cholesterol was hovering around 300 mg: 240 and over is considered high. And his high density lipoprotein or HDL, the so called good cholesterol was so low he seemed destined for the cardiac ward. When HDL levels fall below 35, heart attacks are likely to follow, and Dagnoli’s : 12 mg were at rock bottom. But he seemed very healty when checked over.

Because cholesterol levels are heavily influenced by heredity, Sirtori took blood samples from members of Dagnoli’s family. His father and two of Dagnoli’s three children had similarly bizarre measurements. Yet all of them including the 78 year old patriarch, were perfectly healthy, Sirtori didn’t think Dagnoli was headed for a heart attack, but he didn’t know what was going on.

Sirtori sent samples of Dagnoli’s blood to his colleagues, asking for ideas. 4 years later his search finally paid off. Analysis of Dagnoli’s HDL showed that a genetic error had changed one of the proteins on the surface of the HDL. The protein called Apo A-1, consists of a chain of 243 amino acids. Dagnoli had the “wrong” amino acid inserted in position 173. So did his father and 2 children. That tiny change had enormous consequences. Sirtori and other investigators found that while the mutated HDL was made at the normal rate, it was quickly broken down, accounting for its low levels. Fortunately for its carriers, it also seemed to be super efficient at its job.

Sirtori named the mutant Apo A-1 Milano and started thinking about where the mutation might have come from. In 1981 he went to Limone and convinced every villager over the age of 10 to give him a sample of blood. Out of a population of 1000, he uncovered a total of 28 carriers. Since then, several more carriers have been found. As the number of portatori grows so does the scientific fascination with this strange gene. For by solving the mystery of why theses Limone villagers remain free of heart disease, researchers hope to answer a more ponderous question : Who among the rest of us is fated to get it ?

Space Saving For Packing Your Stuff

Do you know, A young boy was once shown a large empty glass jar with a screw top lid, then he was handed a box of tennis balls and been asked to fill the jar. He started pour in some tennis balls and then moved them around a bit to try to squeeze in another tennis ball before screwing down the whole lid. The question is : is the jar full ? Yes, it is full, he replied. But then he was given a b

ox of marbles and been asked again to see if he could fit any more in the jar. He started open the lid and found that he could fit quite a few marbles in between the tennis balls. Giving the jar a shake now and then allowed the marbles to settle into the spaces. Actually, he could not fit in another marble and announced that the jar was now full. His Senior then produced a bag of sand and asked the boy to fill the jar again. He unscrewed the lid and poured the sand into the top of the jar. Now he did not need to fiddle around very much at all, just give the jar a careful shake now and again to make sure that the sand was pouring into all the empty nooks and crannies between the tennis balls and the marbles. At last he could not fit any more sand in the jar and screwed the lid back down again. The jar really was full.

From the above story, there are some lessons to be learned. If the boy had been given the sand first and asked to fill up the jar, then there would not have been any room to fit in any marbles or tennis balls afterwards. You need to start with the biggest things if there is to be any room for them at all. The same applies to more familiar packing problems. If you need to move lots of packages into a van then you might want to know how you should set about loading them in order to have the best chance of getting them all in. Our story above shows why you should start with the largest objects and then pack the next largest and so on, leaving the smallest until last.

The shapes of the things you are trying to pack clearly matter. Even they are all the same size. If you are a manufacturer of sweets or other small food items, you might want to know what shape they should be in order to fit as many as possible into a jar or some other large storage container. For a long time ago, it was thought that the answer was to make them all little spheres like gobstoppers. Lots of little spheres seemed to give the smallest amount of empty space in between the closely packed balls. Interestingly it turned out that this was not the best shape to use. If sweets are made in the shape of little ellipsoids rather like mini rugby balls or almonds then more of the space can be filled by them. So some big company fill a volume more efficiently than any collection of identical spheres. If the ellipsoids have their short to long axes in the ratio of 1 to 2, then they leave just 32% of the space empty compared with 36% if they were made into spheres. This seemingly trivial fact has many important consequences for business efficiency and industrial manufacture, reducing wastage, shipping costs and the avoidance of unnecessary packaging.

Multiple Effect of Thermal Instability

I had an odd experience few years ago while staying in a new hotel in Liverpool during an unexpected snowfall. The hotel was a new boutique style of establishment in greatly altered premises dating back to the 19 century commercial heyday of the city. In the early morning I had a tortuous journey thru heavy snow from Manchester by a slow train that was eventually halted for a significant time after an announcement by the driver that the signal cabling along the next stretch of track had been stolen overnight, another market pointer to the steadily growing value of copper, I noted. Eventually by means of coordinated mobile phone calls, the train moved slowly past all the signals set by default at red and trundled safely into the station.

My hotel room was cold and the temperature outside the snow covered skylight windows comfortably below zero. The heating was under floor and so rather slow to respond, and it was difficult to determine whether it was answering to changing the thermostat. Despite assurances from the staff that the temperature would soon rise, it seemed to get colder and eventually a fan heater was brought to help out. Someone at reception suggested that because the heating was new it was important not to turn it up too high.

Much later in the afternoon the building engineer called by, much concerned by the old wives tale about not turning the heating up too much because it was newly installed and like me confused by the fact that the heating was working just fine in the corridors outside, so much so that I left my door open. Fortunately the master panel for all the room heating was just opposite my door and so we looked together at what it revealed before the engineer investigated the temperature in the room next door where the guest had left for the day. It was very warm next door.

Suddenly the engineer realized what was cause of our problem. The heating in the room next door had been wired to the thermostat in my room and my heating to next door’s thermostat. The result was a beautiful example of what engineers would call a Thermal Instability. When my neighbors  felt too warm they turned their thermostat down. As a result my room got colder, so I turned the temperature up on my thermostat which made them feel warmer still so they turned their thermostat down even further making me colder still, so I turned my head up even more, fortunately they gave up and went out.

This type of instability feeds upon the isolated self interest of two players. Some more serous environmental problems can arise because of the same sort of problem. If you run lots of fans and air conditioning to keep cool, you will increase the carbon dioxide levels in your atmosphere, which will retain more of the sun’s heat around the earth, which will increase your demand for cooling. But this problem can not be solved by a simple piece of rewiring.