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Ischemic Heart Disease: The Copper Deficiency Theory
Ischemic heart disease, the leading cause of death in the United States, has long puzzled researchers. While high serum cholesterol levels are linked to cardiovascular risk, the role of dietary fat remains unclear. The copper deficiency theory, suggesting a strong link between decreased copper intake since the 1930s and the rise of ischemic heart disease, can provide a new perspective on prevention and treatment.
Ischemic heart disease, the leading cause of death in the United States, became increasingly common during the 20th century. Its etiology remains obscure. Increased serum cholesterol predicts cardiovascular risk, and thousands of medical articles have described the effects of dietary fat on cholesterol metabolism. However, more than 50 studies of various populations have failed to associate fat intake with risk. Other characteristics predictive of cardiovascular risk include electrocardiographic abnormalities, glucose intolerance, and high blood pressure. Uric acid is so closely associated with risk that the Framingham multivariate analyses corrected for uric acid levels.
However, if the incidence of a disease, in this case heart disease, changes over time, one might expect similar changes in the suspected causal agents. Dietary fat has not changed in the US for a century. In contrast, dietary copper has decreased since the 1930s.
Deficiency diseases, such as beriberi, pellagra, and scurvy, have nearly disappeared in the US. Inspired by the now well-known protective effect of hard drinking water on heart disease, I began to study trace elements and discovered fifty years ago that rats deficient in copper have very high cholesterol levels. This discovery prompted a search for characteristics of animals deficient in copper and relationships between copper metabolism and heart disease. Feeding cholesterol to animals also has produced similarities to heart disease because cholesterol feeding induces copper deficiency.
Recently, more than 30 men and women have been depleted of copper with care. Some people had abnormal blood pressure responses, abnormal heartbeats, high cholesterol, and glucose intolerance. One of the experiments was modified because some men experienced severe tachycardias, heart block, and a heart attack.
At least 80 anatomical, chemical, and physiological similarities exist between people with ischemic heart disease and animals deficient in copper. Coronary artery thrombosis, decreased cardiac copper, hyperuricemia, heart blocks, glucose intolerance, and myocardial infarction are among the more important. Recently, paraoxonase was found decreased in copper deficiency. This enzyme destroys homocysteine thiolactone, which inhibits an enzyme required for the synthesis and repair of arterial connective tissue.
Sugar-sweetened beverages and soft drinks have also been associated with increased heart disease risk. Two-thirds of sugary beverages likely contain "soft" water [1] without copper. While sugars, especially fructose, interfere with copper metabolism in animals, the use of "hard" water in beer and wine may contribute to the protective effect of alcoholic beverages on heart disease risk.
Identifying individuals with low levels of copper can be difficult; serum copper is increased by inflammation, and recent research suggests that serum copper should be corrected for the degree of inflammation present. Newer tests, such as enzyme activity of superoxide dismutase in red blood cells, should be used more widely. This enzyme defends against oxidative stress.
Our daily copper requirements must be determined by depletion studies. For copper, this amount is 0.7mg/day; the recommended dietary allowance (RDA) is 0.9mg/day. Diets with less copper than the RDA for copper are typical. It is unknown if men have a different copper requirement than women.
The copper deficiency theory on the etiology and pathophysiology of ischemic heart disease is the simplest and most general theory on the etiology and pathophysiology of ischemic heart disease that has been proposed because it encompasses the observations of Barker concerning small babies, McCully concerning homocysteine, and Sullivan concerning iron overload.
Tests of this theory need not involve hundreds of patients, as is the case with many current therapeutic studies on heart disease. A small study of septuagenarian patients with chronic heart failure and ischemic heart disease showed that a supplement containing copper improved left ventricular function and quality of life over ten months. More research on copper may lead to the disappearance of ischemic heart disease.
[1] Hard water contains high concentrations of calcium and magnesium. Water softeners replace these elements with sodium.
Undiagnosed Valvular Heart Disease Prevalent In Older Adults
Almost one-third of people over the age of 60 have valvular heart disease, although less than 3% have clinically significant disease, according to new registry data from the United Kingdom. The authors argue their findings support the need for a universal screening program in the elderly to identify and treat disease before it becomes dangerous.
Previous research has demonstrated that elderly patients with aortic stenosis tend to present late in their disease course, having ignored symptoms or attributing them simply to old age. This often worsens their prognosis, potentially leaving them beyond the reach of treatments.
"The first thing that we hope this study would achieve is to put it out there that valvular heart disease is not uncommon," senior author Vassilios S. Vassiliou, MBBS, PhD (Norwich Medical School, University of East Anglia, England), told TCTMD. "It's not uncommon at all. And therefore, if individuals have symptoms that are consistent with valve disease, they [and] family physicians should consider that as opposed to putting it down to just old age."
Secondly, he added, "we're hoping this study will start a conversation about screening. At which stage will screening for valvular heart disease be suitable? This is a very complex area, because it depends on the type of healthcare system in which people are working and it depends a lot on how much echocardiography and ultrasound of the heart cost."
Commenting on the findings, Sreekanth Vemulapalli, MD (Duke University School of Medicine, Durham, NC), told TCTMD they confirm on a larger scale what was seen in the OxVALVE-PCS study, in which 51% of 2,500 UK-based individuals aged at least 65 years had any undiagnosed valvular heart disease, including 6.4% with clinically significant disease. The main strengths with the current study are that it recruited patients from multiple locations and outside of the traditional clinical setting, he said.
Together, these studies reinforce the need for greater awareness among both patients and physicians alike of how prevalent valvular heart disease actually is among elderly people, according to Vemulapalli. "If you're a member of the public and you're experiencing shortness of breath, swelling, or chest discomfort—any of these things which might be coming from valve disease—you should be telling your doctor, 'Hey, I'm having these symptoms and one of the possibilities may be valve disease,'" he said. "On the other side for providers, they need to know that there's substantial prevalence of this disease amongst their older population."
Many practitioners don't routinely use their stethoscopes to auscultate patients, Vemulapalli pointed out. "You can't possibly pick up valve disease without that, and they're not necessarily thinking about it," he said. "These kinds of studies should serve to say: 'This is out there and you need to keep it in mind.'"
A Quarter With Unknown Disease
For the study, Vasiliki Tsampasian, MSc (Norwich Medical School, University of East Anglia), Vassiliou, and colleagues invited more than 10,000 seemingly healthy adults aged ≥ 60 years in the United Kingdom between 2007 and 2016. In total, 5,429 volunteered to answer a health questionnaire and undergo a clinical examination and transthoracic echocardiography, and 4,237 (mean age 69.1 years; 52.2% female; 97.7% white) were eligible to be included in the study population.
More than one-quarter of individuals (28.2%) had some sort of valvular heart disease, with 13.8%, 12.8%, and 8.3% of disease affecting the tricuspid, mitral, and aortic valve, respectively. The rate of clinically significant disease was 2.4%, with 2.2% being moderate and 0.2% severe.
On multivariate analysis, age was the only risk factor associated with an increased chance of developing valvular heart disease in this population (OR 1.07 per year; 95% CI 1.05-1.09). Researchers calculated the number needed to scan to identify one case of valvular heart disease was 42 for adults at least 60 years old and 15 for those at least 75 years old.
Vassiliou said he was surprised at the extent of unknown disease in the study population. "We knew the number was going to be high, but perhaps we didn't expect it to be that high," he said, adding that the rate of significant disease was "reassuringly" low.
The data make the case for a universal screening program for patients over the age of 75, according to Vassiliou. While this undoubtedly would pick up previously undiagnosed disease and potentially increase the equity with which patients with valvular heart disease are treated, he said, he did acknowledge the increased costs associated with such a program as well as the potential to needlessly increase worry for patients.
More Evidence Needed
Indeed, "many of those patients are going to die from other diseases or have more pressing medical problems than their moderate or severe valve disease," said Vemulapalli. "For me to have confidence in calling for screening for all these patients, I would want to see a prospective study that looks at doing the screening and then when you pick up these patients with moderate or severe valve disease, what happens to them in terms of their therapies? And do we actually make a difference in terms of cardiovascular events and cardiovascular death by having a screening program?"
Rather, he would like to see efforts to better identify the patients who need treatment as opposed to waiting for them to see their doctors with symptoms. Potential avenues for this might be using ECG or other routine diagnostic tests to identify valvular heart disease, he suggested.
Vassiliou said he would also like to see similar studies undertaken around the world, this time enrolling a more diverse patient population. Finding medications that can either improve heart function or slow down progression in patients with valvular heart disease also should be a focus, he said.
"Over the years, valve patients tended to be the ones that were not really a priority for government and for healthcare resources, but I think we find that these are a lot more complex than what we had thought of 20, 25 years ago," Vassiliou concluded. "Therefore, I think there should be a lot more investment in the formal research and education of the patients with valve disease."
When The Doctor Says Your Disease Is Just Stress
Amina AlTai had always prided herself on her drive and resilience. When she began experiencing brain fog and fatigue, Ms. AlTai, 39, simply thought it was from working long hours in her marketing job. So she started writing down reminders to keep herself on track. But then her hair started falling out, she gained and lost a lot of weight and she started having gastrointestinal issues.
Ms. AlTai was certain that something was wrong. But the first six doctors she saw didn't take her seriously, she said. Some told her she had so much hair that losing a little bit shouldn't be a problem. Several said she seemed healthy, and dismissed her symptoms as simply stress. It was only when another physician ordered blood tests that Ms. AlTai was diagnosed with Hashimoto's disease and celiac disease, two autoimmune conditions that can damage the thyroid and the small intestine.
"They called me and told me, 'Don't go into work. Go to the hospital instead, because you're days away from multiple organ failure,'" Ms. AlTai remembered. The two chronic diseases had upended her ability to regulate hormones and absorb critical vitamins and nutrients.
Scientists now know that stress is intimately linked with many chronic diseases: It can drive immune changes and inflammation in the body that can worsen symptoms of conditions like asthma, heart disease, arthritis, lupus and inflammatory bowel disease. Meanwhile, many issues caused by stress — headaches, heartburn, blood pressure problems, mood changes — can also be symptoms of chronic illnesses.
For doctors and patients, this overlap can be confusing: Is stress the sole cause of someone's symptoms, or is something more serious at play?
"It's really hard to disentangle," said Scott Russo, director of the Brain-Body Research Center at the Icahn School of Medicine at Mount Sinai.
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