Laboratory testing plays a vital role in keeping tabs on aging women
By Karen Appold

Heart disease is responsible for one in every four female deaths, and is the leading cause of death in women over 40 years old and after menopause. Laboratory testing plays a major role in monitoring the cardiovascular health of women whose risk of heart disease increases with age.

Heather M. Hurlburt, Harvard Medical School

Heather M. Hurlburt, Harvard Medical School

“The loss of natural estrogen may contribute to a higher risk of heart disease,” says Heather M. Hurlburt, MD, director of noninvasive imaging for Brigham and Women’s Cardiovascular Associates at Kent Hospital, Warwick, RI, and an instructor of medicine at Harvard Medical School.

When natural levels of estrogen decline, the rate of atherosclerosis—the gradual layering of cholesterol and fat in the walls of the arteries—increases. “While this process begins very early in life, the rate of atherosclerosis rises rapidly in postmenopausal women,” explains Donna P. Denier, MD, a clinical cardiologist at South Nassau Communities Hospital, Oceanside, NY. “Changes in the walls of blood vessels—referred to as endothelial dysfunction—and increases in fibrinogen levels in the blood facilitate the formation of plaque and clots, which can lead to heart attacks.”

One of the most significant observations after menopause is the change in a woman’s lipid profile. With aging, total cholesterol rises equally for men and women. Among women, however, the makeup of that total changes dramatically. The levels of high-density lipoprotein (HDL) cholesterol, or “good cholesterol,” formerly high, start to decrease. At the same time, levels of low-density lipoprotein (LDL), or “bad cholesterol,” begin to climb.

“Increases in triglyceride levels are also an important factor in cardiovascular risk and are a component of metabolic syndrome,” says Denier.

Menopause also contributes to other risk factors for coronary artery disease (CAD), such as obesity. “Most women find it suddenly harder to lose weight, and notice a different distribution of that weight around the waistline,” says Denier.

“Central obesity is a risk factor for metabolic syndrome and diabetes, and confers a higher risk for CAD than weight on the hips and thighs,” she adds. Menopause can contribute to depression, increased stress levels, poor eating habits, lack of proper sleep, and a more sedentary lifestyle—all contributing to higher risk of CAD.

Other risk factors for CAD also increase as women get older. Hypertension is an important risk factor for the development of CAD, and is more prevalent in men than women until age 45. Among both men and women aged 45 to 64, the rates of hypertension are similar. But after age 64, the rate becomes higher for women. Obesity increases the risk for hypertension, as well as for diabetes and hyperlipidemia.

“Smoking seems to be a more powerful risk factor for women than men,” Denier adds. When compared to male smokers, she observes, “Women who smoke have twice the chance of developing a heart attack.”

THE LAB’S ROLE

John P. Higgins, Lyndon B. Johnson General Hospital, University of Texas Health Science Center

John P. Higgins, Lyndon B. Johnson General Hospital, University of Texas Health Science Center

According to the American Heart Association, from 2007 to 2010 the prevalence of coronary heart disease in women was 5.5% for women aged 40 to 60, 10.6% for women aged 60 to 79, and 18.6% for women aged 80 and older.

Laboratory testing plays a vital role in the diagnosis and management of women with heart disease. Here are some of the more common tests.

Cholesterol. The fasting lipid profile is used to stratify a person’s risk of heart disease. There are multiple components of this test:

Total cholesterol. This is a sum of the blood’s cholesterol content. A high level indicates increased risk of heart disease. Ideally, total cholesterol should be below 200 mg/dL (5.2 mmol/L), says John P. Higgins, MD, associate professor of medicine and chief of cardiology at Lyndon B. Johnson General Hospital, University of Texas Health Science Center at Houston.

LDL cholesterol. Also known as bad cholesterol, because high levels contribute to fatty deposits (plaques) in arteries, which reduces blood flow. Plaques sometimes rupture and lead to heart attack and stroke. Ideally, an LDL cholesterol level should be less than 130 mg/dL (3.4 mmol/L).

HDL cholesterol. Also known as good cholesterol because it helps carry away LDL cholesterol. Ideally, HDL cholesterol levels should be 60 mg/dL (1.6 mmol/L) or higher.

Triglycerides. Another type of fat in the blood, triglycerides at high levels usually indicate a person is regularly eating more calories than they are burning. High levels increase risk of heart disease. Ideally, triglyceride levels should be less than 150 mg/dL (1.7 mmol/L).

Recently updated guidelines have suggested four groups of people for whom cholesterol lowering or statin therapy is likely indicated, says Hurlburt. These include any adult with an LDL level greater than 190, diabetic patients between the ages of 40 and 75, patients with known atherosclerotic cardiovascular disease (ASCVD), and adults with an increased 10-year risk of ASCVD as assessed by a standardized risk calculator. Attention is also given to the levels of HDL and triglycerides.

C-Reactive Protein (CRP). This protein is produced by the liver as part of the body’s response to injury or infection (inflammatory response). Inflammation plays a central role in the process of atherosclerosis. In the general population, women have higher levels of CRP than men. Nevertheless, elevated serum CRP predicts cardiovascular disease (CVD) in women as well as men.

Low-, intermediate-, and high-risk CRP values have been defined as less than 1, 1 to 3, and greater than 3 mg/L, respectively. The use of high-sensitivity CRP testing (hs-CRP) to screen the general population for cardiovascular risk is controversial, as many other medical conditions can also elevate this lab value.

Brain natriuretic peptide (BNP). This protein in the bloodstream is released by heart cells as a result of increased heart wall stretch. Serum BNP is increased in patients with congestive heart failure and is a predictor of death and cardiovascular events in asymptomatic patients without congestive heart failure.

Fibrinogen. This protein in the bloodstream helps blood to clot. Too much fibrinogen can cause a clot to form in an artery, leading to a heart attack or stroke. High levels may indicate atherosclerosis and can injure the artery wall. Smoking, inactivity, drinking too much alcohol, and taking supplemental estrogen (birth control pills or hormone therapy) may increase one’s fibrinogen level. A normal fibrinogen level is considered to be between 200 and 400 mg/L.

Homocysteine. This is an amino acid used to make protein and to build and maintain tissue. Increased homocysteine levels may increase the risk of stroke, certain types of heart disease, and disease of the blood vessels of the arms, legs, and feet (peripheral artery disease). A normal homocysteine level is between 4.4 and 10.8 µmol/L.

Lipoprotein (a) or Lp(a). This type of small, dense LDL cholesterol is determined by one’s genetic makeup and isn’t generally affected by lifestyle. High levels of Lp(a) may point to increased risk of heart disease.

RECENT ADVANCES

Ongoing cardiology research is forwarding the development of both medical tests and treatment strategies for heart disease. “Advances range from diagnostic lab tests for asymptomatic patients to advanced cardiac imaging, as well as surgical and device therapies for patients with advanced heart disease,” says Hurlburt.

Traditional risk-factor assessment has been ineffective at stratifying women according to their risk of heart disease, prompting the emergence of novel markers and prediction scores to identify the population at risk. “Sex differences in the manifestations and pathophysiology of CAD have also led to differences in the selection of diagnostic testing and treatment options for women,” says Higgins.

“The frequent finding of nonobstructive CAD in women with ischemia suggests microvascular dysfunction as an underlying cause,” he adds. “Therefore, coronary reactivity and endothelial function testing may add to diagnostic accuracy in female patients.”

TESTING WOMEN FOR CARDIOVASCULAR DISEASE

Luis R. Lopez, Corgenix Medical Corp

Luis R. Lopez, Corgenix Medical Corp

In keeping with the newly recognized need for more sophisticated cardiovascular testing for women, IVD manufacturers have brought forward a variety of new cardiology tests.

In aging women, measuring thromboxane levels is an important tool for clinical management of CVD risk. In most individuals, aspirin inhibits platelet thromboxanes, preventing platelet stickiness and blood clots, and thereby reducing the risk of CVD. But poor inhibition of thromboxane by aspirin (also referred to as “aspirin resistance”) is associated with up to a 13-fold increased risk of atherothrombotic CVD, and has been found to be more common in women
than men.

Aspirin has been shown to reduce the first incidence of stroke and heart attack in men—but not in women over 65 years old. This finding suggests that aspirin’s effect in women is different. When compared to levels among men, thromboxane levels (and platelet activation) are higher among both women and diabetics.

The Corgenix AspirinWorks test kit measures urinary 11-dehydro thromboxane B2 (11dhTxB2), a by-product of platelet thromboxane metabolism and a direct indicator of platelet activation. According to Luis R. Lopez, MD, medical director at Corgenix Medical Corp, Broomfield, Colo, it is the only FDA-cleared test that measures 11dhTxB2 to determine aspirin’s effect in apparently healthy individuals.

Unlike functional platelet tests, which require freshly drawn blood that must be evaluated within 4 hours, the AspirinWorks test is performed on a random urine sample that can be provided in any doctor’s office or patient service center, making the test convenient for both physician and patient, Lopez says.

Thomas I. Koshy, Alere Inc

Thomas I. Koshy, Alere Inc

When monitoring and prevention don’t succeed in preventing heart failure, early initiation of therapy can be crucial for patient outcomes. “When used in conjunction with other clinical information, BNP levels may help risk-stratify acute coronary syndrome patients for hospital admission or direct emergency department discharge,” says Thomas I. Koshy, PhD, senior director for scientific affairs at Alere Inc, San Diego.

Measuring BNP levels has been shown to reduce time to adequate therapy, the need for hospitalization and intensive care admission, length of stay, and the mean total cost of treatment. “BNP levels at the time of admission are powerful predictors of outcomes, predicting death and rehospitalization of heart failure patients,” says Koshy.

Detecting heart failure at an early stage can occur within minutes using the Alere Triage BNP test on the Alere Triage MeterPro, a point-of-care (POC) testing platform. The POC test is CLIA-waived for whole blood.

Laboratories can choose either the POC platform or higher throughput, automated BNP testing using the Alere Triage BNP test for Beckman Coulter immunoassay systems. BNP results are clinically interchangeable between the Alere Triage MeterPro and the Beckman Coulter UniCel DxI 800 or Access 2 immunoassay systems.

Karen Appold is a freelance writer for CLP. For further information, contact CLP chief editor Steve Halasey via [email protected]