Von Willebrand factor in diagnostics and treatment of cardiovascular disease: Recent advances and prospects

Coronary Artery Disease

Coronary artery disease (CAD; also atherosclerotic heart disease) is the end result of the accumulation of atheromatous plaques within the walls of the coronary arteries that supply the myocardium (the muscle of the heart) with oxygen and nutrients. It is sometimes also called coronary heart disease (CHD). Although CAD is the most common cause of CHD, it is not the only one.

CAD is the leading cause of death worldwide. While the symptoms and signs of coronary artery disease are noted in the advanced state of disease, most individuals with coronary artery disease show no evidence of disease for decades as the disease progresses before the first onset of symptoms, often a "sudden" heart attack, finally arises. After decades of progression, some of these atheromatous plaques may rupture and (along with the activation of the blood clotting system) start limiting blood flow to the heart muscle. The disease is the most common cause of sudden death, and is also the most common reason for death of men and women over 20 years of age. According to present trends in the United States, half of healthy 40-year-old males will develop CAD in the future, and one in three healthy 40-year-old women. According to the Guinness Book of Records, Northern Ireland is the country with the most occurrences of CAD. By contrast, the Maasai of Africa have almost no heart disease.

As the degree of coronary artery disease progresses, there may be near-complete obstruction of the lumen of the coronary artery, severely restricting the flow of oxygen-carrying blood to the myocardium. Individuals with this degree of coronary artery disease typically have suffered from one or more myocardial infarctions (heart attacks), and may have signs and symptoms of chronic coronary ischemia, including symptoms of angina at rest and flash pulmonary edema.

A distinction should be made between myocardial ischemia and myocardial infarction. Ischemia means that the amount of blood supplied to the tissue is inadequate to supply the needs of the tissue. When the myocardium becomes ischemic, it does not function optimally. When large areas of the myocardium becomes ischemic, there can be impairment in the relaxation and contraction of the myocardium. If the blood flow to the tissue is improved, myocardial ischemia can be reversed. Infarction means that the tissue has undergone irreversible death due to lack of sufficient oxygen-rich blood.

An individual may develop a rupture of an atheromatous plaque at any stage of the spectrum of coronary artery disease. The acute rupture of a plaque may lead to an acute myocardial infarction (heart attack).

The Widowmaker Heart Attack: Cardiologists Explain The Meaning

Cardiovascular diseases (CVDs) are the leading cause of death worldwide, claiming an estimated 17.9 million lives annually, according to the World Health Organization. Over 80% of these fatalities result from heart attacks and strokes. December is notorious for being the biggest month for heart attacks, with one of the most dangerous being the widowmaker heart attack.

A heart attack, known as a myocardial infarction, occurs when cholesterol and fatty deposits in the arteries supplying blood to the heart rupture. "This leads to a cascade of events that eventually form a blood clot, which, if big enough, leads to a heart artery becoming partially or completely blocked," shares Majid Basit, MD, board-certified cardiologist and interventional cardiologist at Memorial Hermann Health System in Houston.

This information is important for anyone looking to understand the risks of heart disease, whether you're concerned about your own health, worried about a loved one, or simply want to be informed about one of the deadliest medical emergencies.

Ahead, Dr. Basit, Daniel Alyesh, MD, a board-certified electrophysiologist at AdventHealth Porter and South Denver Cardiology, and Rama K. Krishna, MD, FACC, FSCAI, chairman of cardiology and board-certified structural and interventional cardiologist at AdventHealth Waterman Hospital in Tavares, FL, share their expert insights on widowmaker heart attacks, including how they're diagnosed, how they're treated, and—most importantly—how to reduce your risk.

What is a widowmaker heart attack?

Dr. Alyesh explains: "A widowmaker heart attack involves a blockage in a blood vessel running down the front of the heart called the left anterior descending artery (LAD)." This type of heart attack occurs when a cholesterol plaque in the LAD ruptures, triggering the formation of a blood clot that blocks blood flow and damages the heart.

What makes a widowmaker heart attack dangerous is the extensive amount of heart muscle at risk. The LAD supplies more than half of the heart's blood flow, so a blockage in this artery can result in significant damage. "These are larger heart attacks that can cause more damage and weakening of the heart relative to other heart attacks," he adds.

The size and severity of the heart attack can influence outcomes, such as the likelihood of arrhythmias (irregular heartbeats) or the development of heart failure due to muscle injury. Like all heart attacks, a widowmaker also carries the risk of cardiac arrest, making quick medical intervention critical.

Why is it called a widowmaker?

"It is given this title because if [the LAD] becomes completely blocked from a heart attack, it can lead to sudden death," says Dr. Basit.

Dr. Krishna notes that survival rates are grim: Only about 12% of individuals who experience cardiac arrest due to this condition manage to survive.

Widowmaker heart attack symptoms

Recognizing the symptoms of a widowmaker heart attack is essential for timely intervention. Here's what doctors emphasize to watch out for.

Classic symptoms:

Sudden and severe chest pain, often described as intense pressure or a weight on the chest

Pain that can radiate to the shoulder, arm, jaw, or back

Dizziness or lightheadedness

Profuse sweating (diaphoresis)

A feeling of impending doom or fear

Subtle symptoms (more common in women):

Chest discomfort that may mimic indigestion, reflux, or gastritis

Nausea or an upset stomach

Unusual fatigue or shortness of breath

In some instances, heart attacks may occur without noticeable symptoms. These "silent" or asymptomatic heart attacks are more common in individuals with diabetes, those with nerve damage, and women.

Widowmaker heart attack causes and risk factors

Doctors highlight several major factors that can increase the risk of a widowmaker heart attack:

Age: Men over 45 and women over 50

Family history

Smoking

Sedentary lifestyle

Unhealthy diet

Being overweight

Chronic conditions like diabetes, high blood pressure, and kidney disease

Heavy alcohol use

High cholesterol levels

Chronic stress

How a widowmaker heart attack is diagnosed

To diagnose a widowmaker heart attack, doctors often start with an electrocardiogram (EKG) to detect characteristic patterns indicating heart injury. They will also run blood tests to measure troponin levels, a key marker of heart damage, explains Dr. Alyesh.

"The gold standard test is a coronary angiogram, which is a minimally invasive diagnostic procedure where dye is injected into the heart arteries to identify cholesterol or blood clot blockages," he says. Not only does this test provide a definitive diagnosis, but it also allows for treatment to be administered during the procedure if necessary.

Treatment for a widowmaker heart attack

"Initial treatment involves blood thinner injections, medications to relieve associated spasm and relieve anxiety, followed swiftly within minutes to perform coronary angiography," explains Dr. Krishna.

Once the diagnosis is confirmed, interventional cardiologists act quickly to restore blood flow to the heart. They use specialized tools, such as aspiration catheters and clot-dissolving medications, and almost always insert a stent—a tiny, mesh-like device that holds the artery open and maintains proper blood flow.

Dr. Basit notes, "Some patients may also require open heart surgery, but because of advances in minimally invasive procedures like heart stent placement, heart surgery is done less commonly these days."

Time is critical when treating a widowmaker heart attack. "Ideally, from the start of the symptoms to the placement of the stent should be less than 90 minutes," Dr. Basit says.

How to recover after a widowmaker heart attack

Recovering from a widowmaker heart attack depends largely on how quickly it is identified and treated. "We [say] 'time is muscle.' The sooner we fix it, the quicker the recovery," explains Dr. Krishna. However, delays in treatment can lead to complications, including heart failure. This is because damaged heart muscle may not recover fully, resulting in a long-term debilitating condition.

Says Dr. Alyesh: "Cardiac rehab is [also] a critical part of recovery and involves a monitored exercise program which often includes counseling on dietary improvements." In these programs, patients work with exercise physiologists to create personalized workout plans and learn how to make heart-healthy dietary choices, including preparing healthy meals.

Medication also plays a key role in recovery. "After a heart attack, people often take many medications aimed at reducing cholesterol and reducing the risk of clotting with antiplatelet medications," notes Dr. Alyesh. For patients whose heart function has been compromised, additional blood pressure medications may be prescribed to support and strengthen the heart.

How to prevent a widowmaker heart attack

The good news, according to the heart doctors, is that there are steps you can take to prevent a widowmaker heart attack. These include:

Eat a heart-healthy diet: Focus on eating more fruits, vegetables, whole grains, and lean proteins. Reduce your intake of saturated fats, like those found in bacon and other processed meats, to help protect your heart.

Stay physically active: Strive for 210 minutes of exercise per week, including both aerobic activities and weight training, to strengthen your heart and improve overall health.

Quit smoking: Smoking significantly increases your risk of a heart attack.

Manage chronic conditions: Keep your blood pressure, cholesterol, and diabetes under control with regular checkups and lifestyle changes.

Reduce stress: Practice stress management techniques, such as meditation, yoga, or deep breathing. Chronic stress can harm your heart.

Understand your family history: Knowing your family's cardiac history can help you assess your inherited risk and take preventive steps.

Get quality sleep: Prioritize good sleep hygiene. Poor sleep can increase your risk for heart disease. Experts advise seven to nine hours of quality sleep per night.

Dr. Krishna also urges everyone to stay alert to unusual symptoms, such as shortness of breath during routine activities or chest pain during normal exertion. "This should make you promptly visit your doctor and get tested early." Symptoms like unexplained chest pain, heavy sweating, dizziness, or difficulty breathing should never be ignored. In such situations, call 911 and seek immediate medical care.

He also stresses the value of basic life support training: "Family members with basic life support training have saved a lot of their loved ones." Taking the time to learn these skills could make all the difference in an emergency.

About the Experts:

Majid Basit, MD, is a board-certified cardiologist and interventional cardiologist at Memorial Hermann Health System in Houston. He is a fellow of the American College of Cardiology and is an adjunct clinical professor at McGovern Medical School at UTHealth.

Daniel Alyesh, MD, is a board-certified electrophysiologist at AdventHealth Porter and South Denver Cardiology, specializing in the diagnosis and treatment of heart rhythm disorders. His expertise includes managing conditions such as atrial fibrillation, supraventricular tachycardia (SVT), bradycardia, palpitations, premature ventricular contractions (PVCs), and other ventricular rhythm irregularities.

Rama K. Krishna, MD, FACC, FSCAI, serves as the chairman of cardiology and is a board-certified structural and interventional cardiologist at AdventHealth Waterman Hospital in Tavares, FL. He holds certifications in internal medicine, cardiology, nuclear cardiology, comprehensive echocardiography, and comprehensive vascular interpretation.

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SGLT2 Inhibitors Vs DPP4 Inhibitors Linked To Lower CVD Risks In T2D

Sodium-glucose cotransporter 2 (SGLT2) inhibitors, compared with dipeptidyl peptidase 4 (DPP4) inhibitors, are associated with a reduced risk for total cardiovascular disease (CVD) events among patients with type 2 diabetes, according to study results published in JAMA Network Open.

Using electronic medical records from the National Cheng Kung University Hospital in Taiwan, researchers conducted a retrospective study from 2015 to 2021 to evaluate the effectiveness of SGLT2 inhibitor therapy vs DPP4 inhibitor therapy in prevention of cardiovascular events among patients with type 2 diabetes.

The primary outcome was a composite of nonfatal CVD events, including coronary heart disease (CHD), heart failure, atrial fibrillation, stroke, myocardial infarction, and transient ischemic attack.

The study included 8384 patients, of whom 1632 used SGLT2 inhibitors and 6752 used DPP4 inhibitors. After propensity score matching, 1632 pairs of SGLT2 inhibitors (mean age, 57.8 years; 41.2% women; mean HbA1c, 8.6%) and DPP4 inhibitors (mean age, 58.2 years; 40.1% women; mean HbA1c, 8.5%) users were included in the analysis.

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In this cohort study of patients with [type 2 diabetes], a significantly reduced risk of total CVD was associated with SGLT2 [inhibitor] vs DPP4 [inhibitor] therapy; that reduction was lower than that for time to first CVD event.

Among subgroups, 585 patients had an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73m² (kidney impairment subgroup), 1062 had adapted diabetes Complications Severity Index (aDCSI) scores of greater than 0 (diabetic complications subgroup), and 458 had established CVD (prior CVD subgroup). These subgroups showed higher baseline CVD percentages, with CHD rates of 27.9%-28.7% (kidney impairment), 32.5%-34.1% (diabetic complications), and 74.5%-75.5% (prior CVD) compared with 21.0%-21.2% (overall cohort).

The mean follow-up ranged from 2.9 to 4.8 years. The risk for the first composite CVD event did not significantly differ between SGLT2 inhibitor and DPP4 inhibitor use among the overall cohort (hazard ratio [HR], 0.90; 95% CI, 0.77-1.05) or kidney impairment (HR, 0.87; 95% CI, 0.71-1.08), diabetic complications (HR, 0.85; 95% CI, 0.73-1.00), and prior CVD (HR, 0.84; 95% CI, 0.70-1.01) subgroups.  

However, SGLT2 inhibitor vs DPP4 inhibitor use was linked to lower CVD recurrence rates among the overall cohort (49.4% vs 51.8%), kidney impairment subgroup (54.1% vs 57.5%), diabetic complications subgroup (51.1% vs 55.7%), and prior CVD subgroup (56.1% vs 65.2%). SGLT2 inhibitor vs DPP4 inhibitor use was also associated with reduced risks for total composite CVD events (HR, 0.82; 95% CI, 0.69-0.98), heart failure (HR, 0.65; 95% CI, 0.49-0.86), and myocardial infarction (HR, 0.57; 95% CI, 0.34-0.95).

Subgroup analyses confirmed the primary findings, with a consistent reduction in composite CVD risk among the kidney impairment (HR, 0.70; 95% CI, 0.62-0.80), diabetic complications (HR, 0.70; 95% CI, 0.64-0.78), and prior CVD (HR, 0.72; 95% CI, 0.65-0.80) subgroups. SGLT2 inhibitor use also provided greater benefit in reducing CVD risk among women than men.

Study limitations include unmeasured confounding, the absence of data on continuity of health care services, and the possibility of treatment misclassification.

The study authors concluded, "In this cohort study of patients with [type 2 diabetes], a significantly reduced risk of total CVD was associated with SGLT2 [inhibitor] vs DPP4 [inhibitor] therapy; that reduction was lower than that for time to first CVD event."

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