American Heart Association's Top 10 Research Advances For
  January 2, 2002

  DALLAS (American Heart Association) -- New treatments for
  heart failure - implantable heart devices and cell-grown tissues
  - are among the top 10 research advances in heart disease
  and stroke for 2001, says David Faxon, M.D., president of the
  American Heart Association.

  Other major milestones include drug-eluting stents and the use
  of stem cell transplants to repair stroke-damaged brains.
  Created in 1996, the "Top 10" list highlights major gains in
  heart disease and stroke research.

  1. Drug-eluting stents to prevent reblockage of coronary
  arteries. In what could become one of the biggest
  breakthroughs in treating cardiovascular disease, scientists
  used drug-coated stents to prevent the reblockage of the
  stented section of a coronary artery. Reblockage occurs in
  about 15 percent to 30 percent of angioplasty patients who
  receive stents. Researchers involved in several clinical trials
  have found that stents coated with a drug prevent the
  overgrowth of cells that typically causes the stented artery to

  The RAVEL study of 238 patients at 19 centers across Europe
  and Latin America compared patients who received a standard
  stent to those who received one coated with Sirolimus, an
  antibiotic that inhibits the overgrowth of cells. The results were
  presented at September's European Society of Cardiology
  meeting in Stockholm. No patients who received the
  drug-eluting stent had restenosis (reblockage) at the
  seven-month follow-up, but 26 percent of those who received
  conventional stents had reblockage. Patients who received the
  drug-eluting stent also had a significant reduction in major
  cardiac events such as heart attack or death during the
  follow-up period (3.3 percent vs. 27.1 percent).

  Results from ELUTES (European Evaluation of Paclitaxel Eluting
  Stent) were presented at the American Heart Association's
  2001 Scientific Sessions in Anaheim, Calif., in November. The
  192 patients in ELUTES were divided into five groups. Four
  groups received a stent coated with varying doses of the
  cancer drug. Patients in the fifth group were used as controls.
  At six-months follow-up, the group that received the stent with
  the highest dose had a 3.1 percent restenosis rate compared
  with a 20.6 percent reblockage rate in the control group. A
  number of other drug-eluting stent trials are under way.

  2. Implantable left ventricular assist devices serve as
  "replacement therapy" for end-stage heart failure. Heart failure
  patients treated with a left ventricular assist device (LVAD)
  lived longer and better than patients who did not receive the
  device. In a study called REMATCH, 68 patients received the
  LVAD and 61 patients were treated with drugs and medical

  Surgeons implanted the pump, which is the size of a compact
  disc player, into the upper part of the abdominal wall or in the
  peritoneal lining. A tube on the device enters the left ventricle
  and drains blood from the ventricle into the device. The pump
  sends the blood to the aorta. Another tube attached to the
  pump extends outside the body and is attached to a
  videotape-sized battery pack, which is worn on a shoulder
  holster. Patients wear a beeper-sized control system on a belt.

  The device assists the heart's left ventricle, which becomes
  weakened in heart failure. The LVAD lets blood pass from the
  left ventricle to the aorta, which supplies oxygen-rich blood to
  the brain and the rest of the body.

  In early human trials, researchers tested the LVAD as a
  "bridge-to-transplant device." This paved the way for its
  ultimate use - a long-term heart replacement therapy for
  patients not eligible for heart transplants. An estimated 50,000
  to 100,000 people with end-stage heart failure could benefit
  from this type of therapy.

  3. Implantable heart showing promise. On July 2, 2001,
  59-year-old Robert Tools became the first person to receive the
  AbioCor implantable heart. He lived for 151 days. Cause of
  death was severe abdominal bleeding according to his
  physician Robert D. Dowling, M.D., of Jewish Hospital in
  Louisville, Ky., who performed the procedure. Jewish Hospital is
  one of five sites participating in the AbioCor artificial heart
  clinical trial.

  Tools, like other patients in the trial, had severe heart failure
  and was too ill for a heart transplant. The trial determined
  whether the implantable heart can extend life with acceptable
  quality for patients with less than 30 days' life expectancy, and
  for whom no other therapeutic alternative exists. To be
  accepted, patients must have severe heart failure affecting
  both the left and right ventricles of the heart and have a life
  expectancy of no more than 30 days.

  The heart is implanted in the chest and mimics the function of
  the human heart by circulating blood through the body. It is
  battery-operated and weighs only about 2 pounds.

  The heart may eventually be an alternative for patients who
  are candidates for heart transplants but for whom no donor
  human heart is available. An estimated 4.7 million Americans
  have congestive heart failure. Many of them would be
  candidates for a heart transplant, but only about 2,000 donor
  hearts are available each year in the United States.

  4. Tissue engineering with bone marrow and cord blood grows
  heart parts. Cardiovascular surgery requires replacement parts
  such as heart valves, blood vessels and vascular patches, but
  their function may be complicated by blood clots, tissue
  overgrowth, limited durability, infection and the inability to
  grow. The body can reject donor tissue. Tissue engineering
  using a patient's own blood or cells offers an alternative
  source. It holds particular promise in pediatric surgery where a
  graft with growth potential is important.

  Researchers at the University Hospital Zurich in Switzerland
  used human bone marrow cells as a new cell type to engineer
  heart valves in the laboratory. The cells were seeded on heart
  valve scaffolds made from bioabsorbable materials and grown
  in a pulse duplicator bioreactor system that mimics the blood
  circulation of humans.

  Heart valves open and close to let blood flow in only one
  direction as it is pumped through the heart's chambers. Each
  valve has several flap-like structures, called leaflets or cusps.

  The engineered human valves opened and closed
  synchronously in the pulse duplicator system. Microscopic
  examination showed an even cell growth and mechanical
  function was comparable to natural human heart valves.

  In 1999, this group was the first to grow a complete heart
  valve in the laboratory in a study that used cells from sheep
  blood vessel walls. The valves showed excellent functional
  performance in blood circulation and strongly resembled natural
  heart valves. Another group used early-stage endothelial cells,
  called endothelial progenitor cells (EPCs), from human umbilical
  cord blood to create endothelial layers for cardiovascular tissue
  engineering. EPCs came from cord blood obtained after a
  C-section and were culture-grown.

  The new cells were seeded onto a bioabsorbable polymer
  scaffold to make tissue strips with the potential to be molded
  into any form (valve, vessel, patch, etc.). The cells were treated
  with vascular endothelial growth factor (VEGF) and fibroblast
  growth factor (bFGF) to stimulate cell growth. The treated cells
  were grown in a pulse duplicator system for two weeks. The
  cells formed capillary-like tubes, indicating the start of blood
  vessel formation.

  The researchers concluded that human umbilical cord blood is a
  valuable source of EPCs, providing novel cells for tissue
  engineering. The exciting possibilities for this cell source include
  "banking" the cells for future use. Cord blood cells could
  potentially be used to create a tissue-engineered structure
  needed to correct a cardiac birth defect diagnosed prenatally.
  The new tissue could be ready to use when the baby is born -
  or even before birth for potential prenatal/fetal surgical repair.

  In other cell transplant experiments, adult human cardiac
  myocytes (heart muscle cells) regenerated after heart attack.
  This means the heart may be able to replace damaged tissue
  by producing new functional cells. A subpopulation of myocytes
  that is not "terminally differentiated" re-entered the cell cycle
  and divided after the infarction. In similar research, adult stem
  cells derived from bone marrow regenerated, forming new
  functional heart cells when injected around the site of the heart

  5. Gene therapy shown to reduce angina. Experimental
  treatments using genes for vascular endothelial growth factor
  (VEGF) are not new. But in 2001 researchers brought a new
  twist to this pioneering treatment for coronary artery disease.

  For the first time, researchers have data from a randomized,
  blinded, placebo-controlled trial indicating that blood flow to the
  heart improves after VEGF2 treatment. Patients treated with
  the VEGF2 gene had less angina, increased their ability to
  exercise and had improved myocardial perfusion. Placebo
  treated patients had none of these changes.

  VEGF is a naturally occurring protein that stimulates the
  proliferation and migration of endothelial cells and endothelial
  progenitor cells, leading to formation of new blood vessels. The
  theory is that injecting the gene into the heart triggers the
  growth of new blood vessels in the oxygen-starved heart

  Previous trials suggested that gene transfer of VEGF diminished
  chest pain and increased blood flow to the heart. However,
  those studies used a surgical approach to directly inject the
  gene into the heart. Thus, it wasn't possible to have a
  placebo-controlled trial, a major limitation of the trials.

  In the study, 19 patients with class III or IV angina - the most
  severe chest pain associated with heart disease - received six
  injections in their left ventricle of either a placebo solution
  (saline) or a VEGF2 gene therapy solution. The injections were
  made using a special catheter that can identify areas of the
  heart muscle that lack an adequate blood supply. The patients
  all tolerated the gene delivery procedure without complications.

  Angina improved by two to three classes in eight of 12 patients
  who received the VEGF2 gene. One person reported that
  VEGF2 gene therapy completely eliminated chest pain. None of
  the six placebo patients experienced a significant reduction in
  angina class. The difference in outcome between the VEGF2-
  and placebo-treated patients was statistically significant, a
  surprising fact in this relatively small pilot study. A large,
  randomized trial is being planned.

  6. Cholesterol-lowering drugs bring benefits to high-risk
  populations, even when LDL is normal. The MRC/BHF Heart
  Protection Study (HPS) is the world's largest randomized trial of
  cholesterol-lowering drugs and of antioxidant vitamins in
  people at increased risk of coronary heart disease (CHD). Even
  though they have been used for decades, statin drugs'
  usefulness in particular populations is unknown. The study is
  one of the first to include substantial numbers of people in
  categories that were excluded from other studies of this kind.

  Patients aged 40-80 with a history of occlusive vascular
  disease or diabetes were eligible, provided their doctors did
  not consider statin therapy a clear choice. Between July 1994
  and May 1997, 20,536 patients were recruited in 69 United
  Kingdom hospitals. Previous heart attack was reported by
  8,510 (most of whom were elderly, female or had "low" total
  cholesterol levels). They also had other forms of cardiovascular
  disease such as previous stroke or TIA, peripheral artery
  disease, diabetes (with overlap between these categories).
  Participants were randomly allocated 40 mg of simvastatin daily
  or matching placebo for 5 ½ years. Vitamins were given to half
  of each treatment group (600 mg vitamin E, 250 mg vitamin C,
  20 mg beta-carotene daily). The other half received a placebo.
  The vitamins had no effect on vascular or related death or

  Cholesterol-lowering therapy reduced total and vascular
  mortality, total CHD, stroke, and revascularization procedures.
  After making allowance for non-compliance (including non-study
  statin use), simvastatin given at 40 mg daily reduced "major
  vascular events" by at least one-third among patients (women,
  people over 70 years old, those with LDL below 3.0 mmol/l [116
  mg/dL] and those with diabetes or non-coronary occlusive
  disease without pre-existing CHD).

  Further development in treating lipid disorders came from
  recommendations from the National Cholesterol Education
  Panel (NCEP). They suggest a new approach to treat adults
  with elevated blood cholesterol. The recommendations, the
  NCEP Adult Treatment Panel III (ATP III), call for physicians to
  use "the basic principle" to match the intensity of the therapy
  to the person's risk. A table that estimates a person's 10-year
  risk is used as a guide for treatment goals. Risk is calculated by
  adding points based on the presence of risk factors such as
  elevated cholesterol, smoking status, blood pressure, HDL and
  age. Individuals with two or more risk factors should be treated
  more intensely.

  Other new features of ATP III focus on treating diabetes,
  multiple metabolic syndrome and other risks factors. The panel
  supports a complete lipoprotein profile: total, LDL and HDL
  cholesterol and triglyercerides, rather than screening for total
  cholesterol or HDL alone. It presents strategies for promoting
  lifestyle changes to reduce risk and drug therapies. The report
  recommends new targets for optimal LDL levels. Optimal levels
  of LDL are 100 mg/dL or less; and low HDL optimal levels
  should be from 35 to 40 mg/dL. The triglycerides classification
  cut point has been lowered.

  Primary prevention of cardiovascular disease should begin with
  reducing intakes of saturated fat, increased physical activity
  and weight control. Secondary prevention should include
  reducing LDL cholesterol below 100 mg/dL by lifestyle changes
  and drug therapy.

  7. New genetic predictors of cardiovascular disease. In one of
  the largest genetic studies of its kind, researchers discovered
  three genetic variants that may explain why some families are
  prone to premature heart disease. Investigators at 15
  institutions used "high throughput" microarray genotyping to
  sift through 62 genes of 352 people with coronary artery
  disease and 418 individuals without. The culprit genes regulate
  thrombospondins (TSP), a family of matrix proteins that helps
  blood clot and repair arteries.

  The investigators discovered distinctive variations in the genes
  of families with coronary artery disease, including a protective
  one. Changes known as single-nucleotide polymorphisms (SNP)
  were observed in genes that encode the different
  thrombospondin proteins. These proteins govern new blood
  vessel growth, blood clotting and the blood vessel response to
  oxidized low-density lipoprotein cholesterol (LDL).

  In the families with coronary artery disease, at least two
  members had a heart attack or coronary revascularization at a
  young age - before age 45 in men and age 50 in women. The
  variant identified as thrombospondin-1 (TSP-1) was associated
  with a nine-fold risk of premature heart attack. Those with the
  TSP-4 variant had an 89 percent greater risk of heart attack.
  The TSP-2 variant was linked to a 69 percent lower heart attack

  Individuals with two copies of one of the variants, called the
  missense variant in thrombospondin-1, had a higher risk of
  early heart disease and the lowest levels of thrombospondin-1
  in blood tests. Individuals with variants of the TSP gene tended
  to have low levels of thrombospondin. The study, the largest
  genotyping of cardiovascular risk to date, may help unravel the
  major causes of death and disability.

  Mutations in another gene called LMNA cause a disease called
  Dunnigan-type familial lipodystropy, in which carriers have a
  six-fold increased risk of coronary artery disease. In particular,
  women with this gene mutation were found to have a markedly
  high rate of coronary artery bypass surgery before the age of
  55. Because the mutant gene was also linked with insulin
  resistance, type 2 diabetes, lipid problems and hypertension,
  this research may help improve the understanding of major
  coronary heart disease risk factors.

  A third gene for Familial Wolff-Parkinson-White Syndrome was
  identified by researchers who conducted genetic studies on 70
  members of a family with the syndrome. The syndrome is the
  second most common cause of paroxysmal supraventricular
  tachycardia (irregular heartbeat). Understanding the genetic
  defects may lead to more specific treatments for the disease.

  8. Cell transplants offer promise for stroke recovery. Rat stem
  cells developed into neurons and other mature brain tissue
  when transplanted into normal and stroke-damaged adult rats.
  This suggests the possibility that brains and spinal cords can
  be repaired following trauma from stroke or other diseases.

  Stem cells - which are found mainly in bone marrow in adults or
  in embryonic tissue - are the blueprint for development of all
  the body's organs, including the brain. They have the potential
  and the flexibility to grow and differentiate into many kinds of
  cells. Until about 10 years ago, many scientists believed that
  the ability to regenerate neurons, or nerve cells, of the brain
  and spinal cord disappeared soon after birth.

  Researchers from Albert Einstein College of Medicine in New
  York harvested embryonic cortical cells (which come from the
  cerebral cortex - the outer layer of the brain) for the
  transplants. The cerebral cortex is the mantle of gray
  substance covering each half of the brain. It's responsible for
  higher mental functions such as thought, memory and voluntary
  movement. This is the area most often damaged by strokes.

  Cortical stem cells were injected into the brains of normal adult
  rats and adult rats damaged by stroke. The cells were marked
  with a chemical that glows when viewed under a fluorescent
  microscope. The stem cells grew in the damaged area, forming
  connections with neighboring cells. Blood vessels were also
  seen growing to nourish the transplanted cells. At 21 to 45
  days after the transplants, most stem cells grew into mature
  neurons and other mature brain cells.

  For his work in this area, the study's lead author, Gaurav
  Gupta, M.D., received the American Stroke Association Mordecai
  Y.T. Globus Young Investigator of the Year Award.

  In another milestone in stroke research at the animal level,
  intravenous administration of bone marrow cells reduced
  stroke-induced disability. Another study showed that
  intravenous treatment

  with adult donor rat stromal cells (mature cells from bone
  marrow) allowed the rats to return to normal or near-normal
  function within 14 days of a stroke. An infusion of a stroke
  patient's own stromal cells may provide benefits and is easily
  given. If the treatment continues to show benefits in animals, it
  may provide new treatments in the future for stroke, brain
  trauma and spinal cord injury in humans. It may also be useful
  in treating Parkinson's disease, multiple sclerosis, Alzheimer's
  and other neurological diseases.

  9. Nurture and nature associated with type 2 diabetes.
  Behavior, rather than genetics, may provide the key to reducing
  a woman's risk of developing type 2 diabetes. Results from the
  Nurses' Health Study suggest that the majority - an estimated
  nine out of 10 cases - of type 2 diabetes could be prevented by
  weight loss, regular physical activity, healthy diet, abstinence
  from smoking, and moderate consumption of alcohol (half to
  one drink per day for women). The risk reduction was similar for
  women with and without a family history of the disease.
  Because diabetes is a major risk factor for cardiovascular
  disease, such modifications may help prevent heart disease.
  Researchers following nearly 85,000 nurses for 16 years
  concluded that an estimated 91 percent of the 3,300 new
  cases of type 2 diabetes diagnosed during the study could
  have been prevented by lifestyle modifications.

  Excess body fat was the single most important risk factor in the
  development of type 2 diabetes. The heavier a woman was,
  the greater her risk of developing the disease, even if she was
  at the high end of a normal BMI (body mass index, a measure
  of body fat). An estimated 97 million Americans are overweight
  or obese.

  Lack of physical activity was also a significant risk, independent
  of body weight. Conversely, women who exercised seven or
  more hours weekly cut their risk by 50 percent compared with
  sedentary women. About 75 percent of the U.S. population is
  considered to be minimally engaged in physical activity or daily

  The women at lowest risk ate a diet high in cereal fiber and
  polyunsaturated fats, and low in saturated and trans fat. They
  abstained from smoking and drank moderately.

  Of the 10.3 million Americans who have diabetes, about 90
  percent have type 2. The number of Americans with diabetes is
  expected to rise as more people become overweight or obese.

  10. Passive smoking not so passive for arteries. Secondhand
  smoke damages the inner layer of the blood vessels, the
  endothelium, providing the first direct evidence of passive
  smoking's link to heart disease. Researchers studied 30
  Japanese men, average age 27, who were exposed to 30
  minutes of passive smoke. A pulsed Doppler echocardiography,
  a test that measures coronary artery blood flow velocity
  noninvasively, provided an indication of coronary circulation,
  including endothelial function.

  In this test, a substance is injected to dilate the resistant
  vessels in coronary circulation. Healthy blood vessels will
  respond in a normal fashion to the stress; injured blood
  vessels will not respond as well. Although passive smoking did
  not reduce active smokers' coronary flow velocity during
  hyperemia, it was reduced significantly in nonsmokers.

  This finding provides evidence of a direct effect of passive
  smoking on the coronary circulation in nonsmokers. And passive
  smoking affects flow reserve in nonsmokers more than in active
  smokers. This reduction in flow reserve indicates the presence
  of endothelial dysfunction, an early process of atherosclerosis
  that increases a nonsmoker's risk for heart disease.