Numbness in the hands: Causes and treatments
Coronary Artery Disease And Women
There's an old myth that heart disease is a "man's disease." The truth is this: It's the leading cause of death for both men and women in the U.S.
The most common type of heart disease is coronary artery disease (CAD). You might also hear the name coronary heart disease. Without treatment and healthy lifestyle changes, it can lead to a heart attack, heart failure, and other serious problems.
If you're a woman, you're just as likely as a man to get CAD. But certain aspects of the disease, like the risk factors and symptoms, can be different for you.
When you understand the differences, you can take steps to prevent CAD, spot possible signs of it early, or get treatment for the condition if you have it.
Women are more likely than men to have health conditions or life situations that up their risk for coronary artery disease. Some of these risk factors only affect women, such as:
These risk factors for CAD tend to be more common in women than men:
Some CAD risk factors seem to make a bigger impact on a woman's risk for heart disease than a man's, including:
The strongest of these risk factors for women is diabetes. Research suggests it triples women's odds of getting CAD. It only doubles the chances for men.
About 8 in 10 women between the ages of 40 and 60 years old have at least one risk factor for coronary artery disease. The more you have, the higher your odds of getting CAD. If you have any of these factors -- or think that you might -- ask your doctor what you can do to lower your chances for CAD. Speak up about it even if the doctor doesn't mention it.
Hormonal changes. Before you start menopause, the hormone estrogen helps protect you from getting coronary artery disease. That's because estrogen boosts your "good" (HDL) cholesterol. It also helps your arteries stay flexible, so they can widen to carry more oxygen-rich blood to your heart. After you go through menopause and your estrogen levels drop, your risk for CAD goes up.
Anatomy differences. In general, a woman's heart and blood vessels are smaller and narrower than a man's to begin with. The muscular walls of a woman's heart are also thinner.
Delays in diagnosis. Women are more likely than men to have types of CAD that are harder for doctors to spot, which means it could take longer to get a diagnosis and treatment.
Many women don't have symptoms of coronary artery disease, or they're different from the "classic" ones that men have. Here's how some CAD symptoms look in women:
Chest pain or discomfort. Your doctor may call this angina. Women with CAD are more likely to have angina while resting. Stress is also more likely to trigger it for them. Men with CAD, on the other hand, tend to get worse chest pain when they're active.
Crushing pressure. Women who have angina or have a heart attack often describe the feeling in their chest as crushing, squeezing, pressure, or tightness. This sensation may flare up in the chest or the neck and throat. Call 911 right away if you think you might be having a heart attack.
Other possible CAD symptoms. Some common ones for women are:
Talk to your doctor if you're having symptoms that worry you. If it turns you out that you have CAD, earlier diagnosis and treatment can lower your chances of dangerous complications.
If you're a woman, ask your doctor these questions to help lower the chances of delays in diagnosis or treatment of coronary artery disease:
Should I get tested for CAD? Doctors are less likely to recommend that women get diagnostic tests for coronary artery disease.
When women go to the hospital with heart-related symptoms, doctors tend to look into other causes first and take longer to refer them for an electrocardiogram (EKG) -- the test that checks for CAD. Women are also less likely than men to get care from a heart specialist during their hospital stay or receive certain types of medications and therapy that could help them.
Younger women are more likely than men to get the wrong diagnosis and go home from the emergency room with symptoms of undiagnosed heart disease.
What are my treatment options? If you learn you have CAD, ask your doctor what treatments work well for women and men.
Women may be less likely than men to get:
The American Heart Association says that lifestyle changes can prevent almost 75% of coronary artery disease cases in women. Try these:
Your heart also reaps the benefits when you get enough sleep and take charge of stress.
Who Is Most Likely To Develop Coronary Artery Disease?
Coronary artery disease is the leading cause of death in the United States. Therapies such as statins, which target high cholesterol levels, can reduce the risk of mortality due to coronary artery disease.
These effects of statins are mediated, in part, by improving blood vessel health. However, there is a lack of therapies for coronary artery disease that directly target the endothelial cells that form the inner lining of blood vessels and influence blood flow.
Identifying genetic risk factors associated with endothelial cell function could help develop therapeutics that target blood vessels.
Research has shown that specific genetic variants are associated with an increased risk of coronary artery disease. These genetic variants regulate the expression of several genes that work together in a small number of major biological pathways.
However, methodological limitations have impeded the identification of major pathways associated with coronary artery disease variants.
A new study using a combination of high-throughput molecular biology techniques and computational methods has identified major biological pathways and novel genes involved in endothelial cell function that could contribute to the risk of coronary artery disease.
The paper reporting the study findings appears in Nature.
Study author Dr. Jesse Engreitz, assistant professor at Stanford University, CA, explained the findings to Medical News Today:
"We found that genetic risk factors for coronary artery disease converge onto a particular pathway in endothelial cells. One of the known roles of this pathway is to tune endothelial cell responses to blood flow, and includes genes that could prove to be good targets for therapies that directly target blood vessels."
"We also found a new understudied gene, TLNRD1, that plays a key role in this pathway in humans and zebrafish but has previously eluded notice. The list of genes we identified might also prove helpful in identifying individuals who are genetically predisposed to having poor vascular health and, therefore, may respond better to existing medications," added Dr. Engreitz.
Advances in genome sequencing technologies have facilitated the discovery of genetic variants associated with several diseases. These genome-wide association studies involve examining genomes from a large number of individuals to identify genetic variants associated with a particular disease.
Several of these genetic variants associated with a disease likely regulate a small number of biological pathways, with each pathway consisting of several genes that work together.
Although genetic variants have been identified for several diseases, linking genetic variants to a few converging biological pathways has been challenging.
A majority of these genetic variants identified by genome-wide association studies do not code for proteins. Instead, these noncoding variants regulate the expression of multiple genes nearby that are involved in biological pathways associated with the disease.
However, identifying the specific genes regulated by each variant and playing a role in disease-associated pathways remains challenging.
Moreover, multiple cells contribute to the development and progression of a disease. Different biological pathways operate in each cell type and contribute to the disease. The specific biological pathways in a particular cell type impacted by disease-associated variants have not been fully characterized.
In other words, how genetic variants identified using genome-wide association studies affect biological function is not well understood. In the present study, the researchers investigated the biological pathways associated with genetic variants that are involved in coronary artery disease.
Dr . Engreitz said: "Human genetics has been immensely successful over the last decades in identifying variants that influence risk for disease — there are now 100,000s of associations between genetic loci and particular human diseases and traits. This vast trove of insights could reveal genes that mediate disease and guide therapeutic development."
"But, it has proven extremely difficult to find the genes, cell types, and pathways underlying each of these associations. Sometimes, it can take a decade to solve this "variant-to-function" problem for even one association," he added.
More than 300 genetic variants have been identified for coronary artery disease using genome-wide association studies. These coronary artery disease-associated variants are known to impact cells associated with blood vessels and hepatocytes in the liver.
In the present study, the authors specifically examined the variants impacting the function of endothelial cells that are present in the walls of blood vessels.
The researchers used laboratory cultures of genetically modified endothelial cells obtained from the human aorta, the blood vessel that carries oxygenated blood to the rest of the body.
The genome of these endothelial cells was sequenced, and then a computational model was used to map genes whose expression was influenced by the coronary artery disease-associated variant.
With the help of data on coronary artery disease-associated variants identified by previous studies, the researchers identified nearly 2,000 genes close to these variants.
Among these genes, the expression of 254 genes was regulated by the coronary artery disease-associated variants.
The researchers then identified the programs or pathways associated with coronary artery disease. They used CRISPR interference (CRISPRi) to individually inhibit the expression of each gene identified in the vicinity of the coronary artery disease-associated variants.
Subsequently, the researchers examined the changes in the gene expression profile of the endothelial aorta cells upon the inhibition of individual candidate genes.
Using computational methods, genes that showed similar patterns of changes in expression profile were categorized as coregulated genes.
These coregulated genes were classified as a biological program or pathway. The analysis generated 50 such programs, several of which were involved in processes that were not specific to endothelial cells or coronary artery disease.
The researchers then examined programs in which the 254 genes regulated by coronary artery disease-associated variants were overrepresented. They identified five such programs, which encompassed 41 coronary artery disease-associated genes and 43 variants.
While these programs included genes that have been implicated in coronary artery disease, a majority of genes in these pathways have not yet been identified as risk factors for this condition.
In addition, all five programs were regulated by genes associated with the pathway associated with cerebral cavernous malformations (CCM), a condition involving the formation of tiny, abnormal clusters of blood vessels in the brain.
Specifically, the analysis revealed that the CCM2 gene and other genes in the CCM pathway were involved in the regulation of all five coronary artery disease pathways.
Previous studies have shown that the CCM pathway modulates the function of endothelial cells in blood vessels and regulates blood flow.
However, CCM2 and other CCM pathway genes have not been shown to be involved in coronary artery disease. The present study found that inhibiting the expression of CCM pathways modulated the expression of genes that have been shown to be involved in coronary artery disease. These findings indicate the involvement of genes in the CCM pathway in coronary artery disease.
The researchers further examined the role of one of the novel CCM pathway genes, TLNRD1. They focused on TLNRD1 because the gene is one of the strongest regulators of the five coronary artery disease pathways. The role of TLNRD1 in endothelial cell function has not been characterized so far.
The researchers found that TLNRD1 interacts with CCM2 and, consequently, examined whether TLNRD1 performed a function similar to CCM2. The disruption of TLNRD1 in cells cultured in the laboratory altered the barrier function of endothelial cells. Such an impaired barrier function of endothelial cells has been implicated in cardiovascular diseases.
In addition, the disruption of the TLNRD1 expression in zebrafish also adversely impacted heart and blood vessel development in a zebrafish model.
These results support the role of the TLNRD1 gene in sustaining blood flow and could be a risk factor for coronary artery disease development.
Besides aiding the identification of new therapeutic targets for coronary artery disease, the methodological approach used by the study could facilitate the discovery of novel biological pathways associated with other diseases.
Dr. Engrietz said: "In this study, we developed a new methodology to extract lessons from human genetic data. Here, we took a new approach leveraging CRISPR tools, which we use to simultaneously break every candidate gene in different endothelial cells in a dish and measure what happens to these cells. From there, we use computational models to learn which sets of genes are working together in pathways."
"With this comprehensive and systematic data, we are able to much better interpret genetic associations and here identify likely causal genes for 40 out of [approximately] 300 loci for coronary artery disease in a single pass. We think this tool will be a powerful approach for studying many other heritable diseases in the future," added Dr. Engrietz.
Dr. Cheng-Han Chen, board-certified interventional cardiologist and medical director of the Structural Heart Program at MemorialCare Saddleback Medical Center in Laguna Hills, CA, not involved in this study, commented that:
"This research has the potential to open an entirely new field of research, as it might be able to identify the molecular connections more efficiently between gene variants and clinical disease. With such a strategy, researchers would then be able to target the biological pathways through therapeutics to improve clinical outcomes."
Why People With Severe Psoriasis Have A Higher Risk Of Heart Disease
Globally, psoriasis affects an estimated 125 million people around the world.
Despite its prevalence, this immune-mediated dermatological condition still holds many mysteries.
Aside from psoriatic lesions on the skin, this condition can also influence less visible parts of the body.
One important example is its links to an increased risk of cardiovascular events. This increase in risk is independent of traditional cardiovascular risk factors, such as smoking, age, diabetes, and hypertension.
Medical News Today spoke with Dr. Joel Gelfand, a professor of dermatology and epidemiology at the University of Pennsylvania Perelman School of Medicine about the disease.
"There are many lifestyle, genetic, and immunologic connections between psoriasis and cardiovascular disease," he explained.
He noted that scientists have known about this link for many years and it is an important area of research.
"The more extensive psoriasis is on the skin, the greater risk the patient has of heart attack, stroke, and mortality," said Gelfand, who wasn't involved in the study. "Underdiagnosed and undertreated, traditional cardiovascular risk factors in psoriasis patients are also critical to mediating this relationship."
A recent study, which appears in the Journal of Investigative Dermatology, uses a new approach to investigate the precise mechanisms behind psoriasis and cardiovascular disease.
Experts say that the inflammation associated with psoriasis helps drive the development of cardiovascular disease.
This inflammation encourages the growth of plaques in blood vessels and can lead to atherosclerosis, a factor in the risk of cardiovascular diseases.
This includes an increased risk of coronary artery disease, where the blood vessels supplying the heart become narrower.
However, there are still some gaps in our understanding. Studies have shown that people with psoriasis have elevated cardiovascular risk before the appearance of coronary artery disease.
Some scientists believe that this may be due to coronary microvascular dysfunction (CMD). The latest study digs into this theory.
CMD affects the tiny blood vessels that supply the cardiac muscle. Like coronary artery disease, inflammation seems to be a driving factor in CMD.
However, while coronary artery disease and CMD are related, according to the authors of the recent paper, they "may play different roles in the pathogenesis of vascular disease."
Some existing evidence suggests that the increased cardiovascular risk in people with psoriasis may be due to CMD, but previous investigations have been small in scale.
The latest study set out to replicate those findings in a larger group.
Because CMD affects the smallest blood vessels, most standard medical procedures cannot detect it. So, in this study, the researchers used a measure called coronary flow reserve, which can detect both coronary artery disease and CMD.
Coronary flow reserve is a measure of how much blood flow to the coronary arteries can increase during exertion. In other words, it assess how much the coronary circulation can dilate to increase its capacity.
In healthy people, coronary flow reserve is between 3 and 6. If someone has a score of 3, this means they can triple the blood flow when needed.
A score of 2.5 or lower indicates either CMD or coronary artery disease. So, if a routine coronary angiography reveals no coronary artery disease, this implicates CMD.
The researchers included data from 448 people with psoriasis.
Of these, they found that 31% had a coronary flow reserve of 2.5 or lower, but no sign of coronary artery disease in a follow-up scan. So, roughly 1 in 3 had CMD.
Compared with participants without CMD, those with CMD were more likely to:
They were also more likely to have more severe psoriasis and to have lived with the condition for longer. So, as disease duration and severity increased, so did the risk of CMD.
Researchers say the results show that disease duration and severity are linked to CMD. Because CMD is prevalent in people with other inflammatory conditions, this supports the theory that systemic inflammation drives CMD.
Also, their analysis found no association between CMD and conventional cardiovascular risk factors, such as smoking, blood fat levels, or type 2 diabetes, all of which are associated with CMD in the general population.
Studies in the general population and people with psoriasis demonstrate that low coronary flow reserves predict poorer cardiovascular outcomes.
The authors conclude that the high levels of CMD are "likely to contribute significantly to the increased risk of adverse [cardiovascular] outcomes in patients with psoriasis […] independently of traditional [cardiovascular] risk factors."
The authors also note that some research suggests that treating psoriasis is associated with reduced levels of CMD. With this in mind, they write:
"[W]e might hypothesize that an early and effective treatment of psoriasis would restore a CMD and eventually prevent the future risk of myocardial infarction and heart failure associated with it."
Gelfand explained how he and his colleagues are also investigating other ways of assessing cardiovascular risk in people with psoriasis.
"The risk of future cardiovascular events can be further refined with cardiac imaging, such as a coronary artery calcium score," he said. "We are testing a novel, centralized, care coordination model to help psoriasis patients get better screening for, and management of, traditional cardiovascular risk factors. Our preliminary data is quite promising."
In the future, using a range of scanning and diagnostic technology might help assess and address cardiac risk earlier in this population.
Because inflammation plays an important role in increasing cardiovascular risk, psoriasis drugs that reduce inflammation may also help reduce this risk.
However, as Gelfand mentioned, the evidence is "quite mixed" at this point.
"To date, TNF [tumor necrosis factor] inhibitors seem to be the most promising for lowering cardiovascular risk in psoriasis, but a causal relationship has not been established," he said.
Successfully treating psoriasis symptoms can also reduce risk in other ways.
"Improved disease control may change how patients live their lives," Axel Svedbom, PhD, a researcher at the Karolinska Institutet in Sweden who was not involved in the latest research, told Medical News Today.
"Patients with well-controlled psoriasis may lead healthier lives due to reduced social stigma and their sleep may improve due to reduced itch — poor sleep is a risk factor for cardiovascular disease," he said.
"Furthermore," he noted, "psoriasis is associated with lipid dysfunction and it is possible that disease activity modifies lipid composition of function. Another potential mechanism is tryptophan metabolism, which has been implicated in both psoriasis and cardiovascular disease."
We still have much to learn about psoriasis. This study adds another piece to the puzzle.
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