February is American Heart Month. Sponsored by the American Heart Association, American Heart Month is a time to battle cardiovascular disease and educate people on what they can do to live heart-healthy lives. Heart disease, including stroke, is the leading cause of death for men and women in the United States.

How much do you know about the condition of your heart? Heart health awareness typically focuses on heart disease in older adults caused by an unhealthy diet and a lack of exercise. But what if you could be at risk for cardiac arrest and sudden death even though you are young and in shape?

Image credit: Heart arrhythmia via Shutterstock

Long QT syndrome (LQTS) is one of several sudden arrhythmia death syndromes, a class of conditions affecting the heart’s rhythm. People can be born with an inherited form of the syndrome or acquire it during their life. LQTS can cause sudden, uncontrollable, dangerous heartbeats in response to exercise or stress. LQTS can arise from mutation of one of several genes, including Potassium Channel, Voltage-gated, KQT-like Subfamily, Member 1 (KCNQ1); Potassium Channel, Voltage-gated, Subfamily H, Member 2 (KCNH2); and Sodium Channel, Voltage-gated, Type V, Alpha Subunit (SCN5A).

LQTS is common; approximately one in every 2,500 people has the disorder [1]. Some people don’t discover they have LQTS until the sudden unexplained death of a family member. However, if identified, LQTS can be treated with medications, limited physical activity, or, in some cases, medical devices or surgery [2].

Dr. Brian Delisle, a faculty member of the University of Kentucky’s College of Medicine, is studying the genetic form of LQTS in order to identify new treatments. According to Delisle, there are several types of the genetic form of LQTS, each caused by a different gene mutation. One form of LQTS syndrome, LQT2 (which involves mutations of the human ether-a-go-go related gene (hERG), also known as KCNH2), is caused by a mutation in a gene that codes for potassium channels in the heart’s cells. The mutation prevents the potassium channels from being transported to their proper place at the cell’s surface. As a result, the potassium channels cannot function properly.

In a recent study published in the American Journal of Physiology Cell Physiology, researchers from Delisle’s laboratory found that a distinct cellular compartment in cardiac myocytes (heart cells) negatively regulates the production and movement of LQT2 [3]. Delisle said:

We do have a series of drugs that can correct this … in cell systems. But the problem right now is that most of the drugs that do this actually cause the acquired form of Long QT.

Delisle hopes that by better understanding the mechanism preventing the proper transport of the potassium channels to the cell’s surface, other therapeutic approaches can be identified to correct this problem.

About the author: Julianne Wyrick is a senior biochemistry major at Asbury University. A 2011 Kentucky Academy of Sciences award winner for scientific research, following graduation Julianne plans to enter a health and medical journalism graduate program.

References

1. Long QT Syndrome. Sudden Arrhythmia Death Syndrome (SADS) Foundation. Accessed 2012 Jan 28.
2. Long QT Syndrome. Mayo Clinic. Accessed 2012 Jan 28.
3. Smith et al. Trafficking-deficient hERG K? channels linked to long QT syndrome are regulated by a microtubule-dependent quality control compartment in the ER. Am J Physiol Cell Physiol. 2011 Jul;301(1):C75-85. Epub 2011 Apr 13.
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One of the major differences between this most recent study and previous analyses of the relationship between alcohol and breast cancer is that the new study was very high-power, meaning that the number of participants was quite large (nearly 75,000 women). The sheer number of study subjects allowed researchers to determine the relationship between low-level drinking and cancer risk with much higher confidence than previous studies, with their fewer participants, had allowed. Another strength of the new study is that it was longitudinal, taking place over 28 years. However, the participants were not assigned to treatment conditions, and the researchers relied upon self-report to track alcohol consumption. Both of these somewhat weaken the results of the study, though in largely unavoidable ways. Self-report relies upon participants to accurately report their alcohol consumption, and can result in inaccurate data if participants misremember or misrepresent their drinking. Further, study results are generally more powerful and more easily generalized to the population if participants are assigned randomly to conditions. Assigning participants helps to remove confounding factors that could partially or fully explain the results. For instance, the researchers reported that the majority of women who drank a moderate amount of alcohol on a regular basis had lower BMI, were more likely to have had natural menopause, and were more likely to be smokers.

Any one of these factors might have impacted breast cancer risk (smoking is the one with the most obvious plausible mechanism), or an unidentified third variable that occurred more commonly among low to moderate drinkers could have increased risk of breast cancer.

The results of the JAMA study are interesting, and certainly support the results of many other studies: cancer risk increases with increasing alcohol consumption. However, the results of this study aren’t necessarily reason in and of themselves to cease all alcohol consumption. Studies also suggest that low to moderate alcohol consumption (about 1-2 drinks per day for men, and one drink per day for women) increases HDL and decreases risk of cardiovascular disease, heart attack and stroke [5,6]. This is because regular, limited amounts of alcohol prevent the buildup of smooth muscle cells in blood vessels that leads to the narrowing of the arteries.

While breast cancer certainly gets more media attention than heart disease, especially where it comes to women’s health, the U.S. Centers for Disease Control and Prevention (CDC) report that heart disease is the number one cause of death in women, resulting in more than a quarter of all female deaths. In an article written for the journal Circulation, Dr. Rose Marie Robertson discusses the misperceptions that so many women have about the relative dangers of health threats [7]. She notes that the vast majority of women believe cancer is their greatest health threat, while fewer than 10% recognize heart disease as such.

Therefore, while few doctors would recommend introducing alcohol for the sole purpose of lowering the risk of heart disease (since alcohol consumption is associated with a number of negative health effects), it would be shortsighted to cease moderate alcohol consumption for the purpose of preventing breast cancer, given its positive impact on the heart. To their credit, the authors of the new JAMA study recognize this, and advise women to talk to their doctors about alcohol, breast cancer, and heart disease.

References

1. Chen et al. Moderate Alcohol Consumption During Adult Life, Drinking Patterns, and Breast Cancer Risk. JAMA. 2011 Nov 2;306(17):1884-1890.
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2. Smith-Warner et al. Alcohol and breast cancer in women: a pooled analy- sis of cohort studies. JAMA. 1998 Feb 18;279(7):535-40.
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3. Dumeaux et al. Useoforalcon- traceptives, alcohol, and risk for invasive breast cancer. Cancer Epidemiol Biomarkers Prev. 2004 Aug;13(8):1302-7.
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4. Longnecker et al. Risk of breast cancer in relation to lifetime alcohol consumption. J Natl Cancer Inst. 1995 Jun 21;87(12):923-9.
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5. Ronksley et al. Association of alcohol consumption with selected cardiovascular disease outcomes: a systematic review and meta-analysis. BMJ. 2011 Feb 22;342:d671. doi: 10.1136/bmj.d671.
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6. De Oliveira E Silva et al. Alcohol consumption raises HDL cholesterol levels by increasing the transport rate of apolipoproteins A-I and A-II. Circulation. 2000 Nov 7;102(19):2347-52.
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7. Robertson RM. Women and cardiovascular disease: the risks of misperception and the need for action. Circulation. 2001 May 15;103(19):2318-20.
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In a study presented last week at the European Society of Cardiology Congress 2011, scientists described new research that examined the relationship between exercise duration, exercise intensity, and total risk of death [1]. Lead researcher Peter Schnohr of Copenhagen, Denmark explained that both male and female cyclists had a decreased total risk of death if they cycled vigorously (by their own perception), but that cycling duration didn’t show a similar protective effect.

Schnohr found that male cyclists who rode at an intense level of effort lived, on average, 5.3 years longer than those who cycled slowly. Men who cycled at moderate intensity lived an average of 2.9 years longer than the leisurely cyclists. For women, vigorous and moderate cyclists lived 3.9 and 2.2 years longer, respectively, than those who rode at a slow pace.

While vigorous cycling was correlated with a reduced risk of death from all causes, the correlation between vigorous cycling and reduced risk of death from coronary heart disease was particularly strong. Across all ages and genders and adjusted to account for differences in activities, risk factors, and behaviors such as smoking, people who rode vigorously for 30 minutes per day had only 18% the risk of dying from coronary heart disease as compared to those who rode slowly.

Coronary heart disease is the leading cause of death for both men and women in the United States [2], and inactivity is a major heart disease risk factor. Currently, the American Heart Association recommends plenty of exercise — at least 150 minutes per week — to decrease risk of coronary heart disease [3].

There are several reasons exercise is though to be so protective against coronary heart disease. People who exercise regularly are less likely to be overweight and have high blood pressure, both of which are risk factors for heart disease. Additionally, exercise can also help improve cholesterol levels, decreasing LDL and increasing HDL.

Schnohr’s latest study strengthens the correlation between exercise intensity and reduced risk of death that he and colleagues first reported in 2007 [4]. The earlier study found that vigorous walking decreased risk of death from all causes more than average-effort walking, which nevertheless showed a protective effect as compared to slow walking.

Despite the emphasis on exercise duration by the American Heart Association, Schnohr was unable to correlate exercise duration with risk of death in either study. Based upon his findings, Schnohr suggests it’s healthiest to find time to exercise vigorously for at least 30 minutes every day of the week.

References

1. Cycling fast: vigorous daily exercise recommended for a longer life. European Society of Cardiology press release. 2011 Aug 29.
2. Heron et al. Deaths: Final data for 2006. National Vital Statistics Reports. 2009 Apr;57(14).
3. American Heart Association Guidelines. Accessed 2011 Sep 4.
4. Schnohr et al. Intensity versus duration of walking: Impact on mortality: the Copenhagen City Heart Study. Eur J Cardiovasc Prev Rehabil 2007;14:72-78.
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Notch proteins are a family of proteins that span across the membrane of cells. They are important for cell proliferation, differentiation and cell death. When Notch proteins are stimulated by high levels of cholesterol, smoking or changes in blood flow, they cause smooth muscle cells to multiply and can lead to the development of arterial plaques. The accumulation of smooth muscle cells together with immune cells is the central cellular feature of atherosclerosis [2].

Blood vessel remodeling — when vessels change shape and thickness in response to injury — occurs as the atherosclerotic plaque within the vessel enlarges. Vessel remodeling plays a pathogenic role in chronic inflammatory diseases such as asthma, COPD, rheumatoid arthritis, Crohn’s disease and skin lesions in psoriasis.

In the current study, researchers first confirmed the inhibitory effect of ethanol on a culture of human coronary artery smooth muscle cells. Compared to untreated cell cultures, ethanol treatment inhibited smooth muscle cell proliferation and caused a small increase in the percentage of cells undergoing cell death.

Looking closer, the investigators found that ethanol treatment significantly decreased Notch 1 gene and protein expression, as well as the expression of Notch target genes (i.e. genes that Notch 1 regulates): Hairy/enhancer of split-related with YRPW motif 1 (HEY1) and Hairy/enhancer of split-related with YRPW motif 1 (HEY2). These results were specific to ethanol; methanol and butanol had no significant effect on Notch 1 expression.

Researchers then over-expressed Notch 1 or the target gene HEY1 in cells. Over-expression blocked the inhibitory effect of ethanol. Conversely, when Notch 1 expression was inhibited, smooth muscle cell growth was blocked to a similar extent as treating cells with ethanol.

In a mouse model of vessel remodeling, the remodeling response was inhibited in mice that received moderate levels of alcohol (equivalent in people to 2 drinks per day). Notch expression was inhibited and vessel thickening was reduced.

These findings may one day help scientists create a treatment for heart disease that mimics the beneficial influence of modest alcohol consumption.

David Morrow, Ph.D., an instructor in the Department of Surgery at the Medical Center, first author of the study and an expert on Notch, said [3]:

At the molecular level, this is the first time anyone has linked the benefits of moderate drinking on cardiovascular disease with Notch. Now that we’ve identified Notch as a cell signaling pathway regulated by alcohol, we’re going to delve deeper into the nuts and bolts of the process to try to find out exactly how alcohol inhibits Notch in smooth muscle cells.

While this all sounds good, the latest dietary guidelines make it clear that no one should start drinking or drink more frequently on the basis of potential health benefits. Additionally, the line between moderate alcohol consumption and too much consumption is thin; once you get to 3-4 drinks per day, mortality rates double and the risk of congestive heart failure, pancreatitis, and certain cancers, including breast, liver, and lung, increase. If you do choose to drink, have only a limited amount. A 12-ounce beer, 5-ounce glass of wine or 1.5 ounces of liquor (80 proof) counts as one drink.

References

1. Morrow et al. Alcohol inhibits smooth muscle cell proliferation via regulation of the Notch signaling pathway. Arterioscler Thromb Vasc Biol. 2010 Dec;30(12):2597-603. Epub 2010 Oct 7.
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2. Raines and Ross. Smooth muscle cells and the pathogenesis of the lesions of atherosclerosis. Br Heart J. 1993 Jan;69(1 Suppl):S30-7.
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3. Well-Known Molecule May be Behind Alcohol’s Benefits to Heart Health. University of Rochester Medical Center. 2010 Nov 18.

The observational study was conducted by Drs. Phyllis K. Stein, Ph.D., from the Washington School of Medicine in St. Louis and Joshua I. Barzilay, M.D., from the Emory University School of Medicine in Atlanta. They measured heart rate turbulence in 1,272 patients aged 65 or older using a 24-hour heart monitoring device called a Holter monitor, which records a person’s electrocardiogram.

Patients were divided into three groups based on their cardiovascular health. Those in the “clinical” group had a history of cardiovascular disease such as a heart attack. Those in the “subclinical” group had some signs of heart disease such as high blood pressure but had never been treated for cardiovascular disease. Those in the “healthy” group had no evidence of clinical or subclinical disease.

Among the nearly 1,300 study participants, heart rate turbulence was an even stronger heart disease risk factor than elevated levels of C-reactive protein (CRP), a potential heart disease biomarker that has emerged in recent years.

Study participants considered at low risk of heart disease based on traditional risk factors were on average 8-9 times more likely to die of heart disease during the 14-year follow-up period if they had abnormal heart rate turbulence values. Traditional risk factors include age, gender, high blood cholesterol, high blood pressure, obesity, diabetes and smoking. Low-risk individuals with elevated CRP in their blood were about 2.5 times more likely to die than those with normal or low CRP.

In the healthy group, even after controlling for other risk factors, abnormal heart rate turbulence and CRP levels both appeared to independently correlate with an increased likelihood of dying of heart disease. Abnormal heart rate turbulence — present in about 7% of the study participants — also predicted an increased likelihood of heart disease death in the clinical and subclinical groups, though these results were not as pronounced.

Study author Phyllis K. Stein, PhD, research associate professor of medicine and director of the Heart Rate Variability Laboratory at the Washington School of Medicine in St. Louis, said [2]:

These are people we do not expect to die of cardiac causes. They appear healthy, but they’re not. We have shown a way they’re not healthy that isn’t showing up using standard tests.

This study is part of the National Heart, Lung and Blood Institute (NHLBI) Cardiovascular Health Study, an NHLBI-funded observational study of risk factors for cardiovascular disease in adults 65 years or older that ran for 10 years, from 1989 to 1999. Study participants underwent annual extensive clinical examinations, which included measurements of traditional risk factors such as blood pressure and lipids as well as measures of subclinical disease, including echocardiography of the heart, carotid ultrasound and cranial magnetic-resonance imaging (MRI).

Dr. Stein said that the measurement reflects how well a person’s nervous system works [3]:

A heart rate turbulence measurement is insightful because it offers a sign of how well the autonomic, or subconscious, nervous system is functioning. If someone’s heart doesn’t react well to these uncoordinated beats that might mean it’s not good at reacting to other issues like sudden stress or severe arrhythmias.

Researchers don’t yet know if abnormal heart rate turbulence can be treated or prevented. Nevertheless, this study shows great potential value for measuring heart rate turbulence in clinical practice, since it suggests that signs of heart rate turbulence may be present a year or more before clinical manifestations of heart disease.

References

1. Stein and Barzilay. Relationship of Abnormal Heart Rate Turbulence and Elevated CRP to Cardiac Mortality in Low, Intermediate, and High-Risk Older Adults. J Cardiovasc Electrophysiol. 2011 Feb;22(2):122-7.
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2. ‘Healthy’ patients at high risk of cardiac death identified. Washington University in St. Louis Newsroom. 2011 Feb 14.
3. NIH-funded study finds new possible risk factor of heart disease. NIH News. 2011 Feb 15.

A biomarker is a molecular signature found in blood, other body fluids, or tissues that reflects a normal biologic process, pathogenic process or pharmacologic process to a therapeutic intervention. A biomarker that has been shown to have clinical validity and utility can be used to identify the earliest stages of disease onset, diagnosis, prognosis, efficacy of a specific drug therapy, toxicological effects of a drug, or disease risk.

Cortisol is a stress hormone produced by the adrenal gland; it’s secretion is increased during times of stress. Several studies have linked chronic stress and risk for cardiovascular disease risk, which includes heart attack, chest pain, stroke, high blood pressure and heart failure [4-5]. Cortisol is usually measured in saliva, serum or urine, all of which measure cortisol levels in the last few hours to days and thus don’t reflect the stress response over a prolonged period of time. In contrast, hair analysis provides a long-term measurement of cortisol production; cortisol can be incorporated into hair and remain stable for at least a 6 month period (corresponding to the proximal 6-cm of a human hair sample).

In 2007, twenty-five healthy pregnant women were evaluated for perceived stress and cortisol levels in hair [6]. Maternal hair cortisol was found to be a potential biomarker of chronic stress in pregnancy, as it correlated positively and significantly with measures of perceived stress. In the present study, a larger cohort of 112 patients was used to evaluate the hypothesis that chronic stress, as assessed by hair cortisol content, is associated with the development of acute myocardial infarction (i.e. heart attack). Although acute stress is increasingly recognized as a contributing factor to acute myocardial infarction (AMI), the role of chronic stress has been less clear.

Hair cortisol concentrations were increased in AMI patients

Patients in the current study were divided into two groups of 56 male subjects above the age of 18 years that underwent hair sampling: a control group and an AMI group. The control group consisted of patients admitted to an internal medicine ward for reasons other than acute coronary syndrome or stroke. The AMI group consisted of patients admitted to the Intensive Cardiac Care Unit at the Meir Medical Center in Kfar-Saba, Israel who were suffering from heart attacks, specifically either ST-elevation or non-ST elevation AMI — this corresponds to the S-T segment on an electrocardiogram (during ventrical systolic depolarization, i.e. when the cardiac muscle is contracted). AMI was defined as the combination of elevated circulating levels of cardiac biomarkers — either troponin or creatine kinase and its MB isoenzyme — with typical chest pain lasting for at least 30 min or typical electrocardiogram changes. None of the study’s participants were admitted to the hospital in the 3 months prior to the study and none of the patients died in either the control or AMI group.

The study evaluated the prevalence of diabetes, hypertension, smoking and family history of coronary artery disease — all risk factors for AMI — between the control and AMI group, but failed to find a difference. However, the AMI group had more cholesterol problems. The researchers found that hair cortisol concentrations in the proximal 3-cm segments of the AMI patients, which corresponds to the last three months, were significantly higher that those of controls. When they looked closer at the AMI patient samples, they were unable to find a difference between hair cortisol levels in the first 1.5-cm and second 1.5-cm segments. When the entire study population (a combination of both control and AMI patients) was divided into quartiles (i.e. dividing the data set into four equal parts so that each part represents one-fourth of the sampled population), the occurrence of AMI increased with hair cortisol concentration (see figure).

The scientists then conducted an analysis using multivariate logistic regression. Logistic regression is a statistical model used for prediction of the probability of occurrence of an event, using predictor variables that may be either numerical or categorical. Their model included factors known to affect the risk for AMI, including age, LDL and HDL cholesterol, BMI, smoking status, previous myocardial infarction, and log-transformed hair cortisol. Only hair cortisol concentrations correlated with AMI.

There are several limitations with this study. First, the analysis only evaluated male patients. AMI is more prevalent in men than women and as there are hormonal differences between men and women, the results should not be applied to females. Second, the study population was small and will need to be corroborated in larger studies. Third, there are limitations to the measurement of cortisol in hair, including length, contamination, and affects of environmental, ethnic and nutritional factors. The researchers also suggest that AMI may be preceded by an escalating restriction in blood supply in the days to weeks prior to a heart attack and thus may have caused stress (rather than stress causing a heart attack). However, the finding that the level of hair cortisol in AMI patients was not statistically different between the first and second 1.5-cm, corresponding to the months leading up to a heart attack, supports the view that hair cortisol levels are a marker of chronic rather than acute stress. Fourth, the study did not consider psychosocial stress nor whether the stress was of physical or emotional nature. Lastly, the study does not address the question of whether, within the group of patients at high risk for a heart attack, the degree of stress would be associated with an increased risk to actually develop a heart attack.

Drs. Gideon Koren and Stan Van Uum — senior authors of the study — developed the method to measure cortisol levels in hair. According to Koren [7]:

Intuitively we know stress is not good for you, but it’s not easy to measure. We know that on average, hair grows one centimetre (cm) a month, and so if we take a hair sample six cm long, we can determine stress levels for six months by measuring the cortisol level in the hair. Stress is a serious part of modern life affecting many areas of health and life. This study has implications for research and for practice, as stress can be managed with lifestyle changes and psychotherapy.

This study demonstrates a novel technique to quantify the accumulation of cortisol in hair over time and suggests that hair cortisol can be used as a biomarker for chronic stress. This study further suggests that cortisol levels are elevated prior to the clinical manifestation of coronary heart disease, supporting the theory that chronic, long-term stress is not healthy and may result in the increased risk for coronary artery disease.

References

1. Rosengren et al. Association of psychosocial risk factors with risk of acute myocardial infarction in 11119 cases and 13648 controls from 52 countries (the INTERHEART study): case-control study. Lancet. 2004 Sep 11-17;364(9438):953-62.
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2. Aboa-Eboule et al. Job strain and risk of acute recurrent coronary heart disease events. JAMA. 2007 Oct 10;298(14):1652-60.
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3. Pereg et al. Hair cortisol and the risk for acute myocardial infarction in adult men. Stress. 2010 Sep 2. [Epub ahead of print]
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4. Steptoe et al. Effort-reward imbalance, overcommitment, and measures of cortisol and blood pressure over the working day. Psychosom Med. 2004 May-Jun;66(3):323-9.
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5. Reynolds et al. Elevated fasting plasma cortisol is associated with ischemic heart disease and its risk factors in people with type 2 diabetes: the Edinburgh type 2 diabetes study. J Clin Endocrinol Metab. 2010 Apr;95(4):1602-8. Epub 2010 Feb 3.
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6. Kalra et al. The relationship between stress and hair cortisol in healthy pregnant women. Clin Invest Med. 2007;30(2):E103-7.
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7. Hair provides proof of the link between chronic stress and heart attack. Western News press release, The University of Western Ontario. 2010 Sep 3.

How you think about your health can have powerful impacts on how you experience your health. In a recent study with a group of cardiac patients, how people thought about their illness (termed “illness cognitions”) was found to have a direct impact on how people experience health and emotional wellbeing [1]. These illness cognitions also affected health indirectly by influencing the types of behaviours people were engaged in to cope with cardiac problems. This study brings to our attention the relevance of psychology in relation to medical illnesses.

Cardiac problems are hugely common across the globe. Cardiovascular disease is the leading cause of death globally and has a significant impact as a chronic disease on quality of life, the economy and healthcare utilisation [2]. Many causes of cardiac problems are preventable — for example by avoiding smoking, taking adequate exercise and maintaining a healthy diet and weight. From a biomedical perspective, treatment for cardiac problems has significantly improved survival rates through drug therapies and surgical approaches [3]. This has caused the treatment focus switch from acute, or short-term, to chronic, or long-term. When living with a long-term health condition, the way people think about their illness becomes extremely important.

Two illness cognitions were focused on in the recent study. First, illness acceptance is an idea commonly talked about and is characterised by a focus on the positive aspects, realisation that the health condition is to be lived with, and an end to the search for a solution to remove the illness. Second, illness-related helplessness relates to feelings that an illness is uncontrollable and has severe consequences for everyday life. Researchers recruited 106 cardiac patients with a range of cardiac conditions. These patients completed questionnaires about their illness acceptance, illness helplessness and how they rated their own health. Six months later, the patients were again asked to complete questionnaires on illness acceptance, helplessness, subjective health and coping strategies they used to deal with their cardiac problems. The goal was to explore whether illness acceptance and helplessness could predict self-rated health. Coping behaviours were also studied. There are many different types of coping, such as soothing oneself, wishful thinking, emotional coping and reactions.

Using a complex statistical technique called “Structural Equation Modelling”, the researchers tested multiple relationships between different variables. The relationships between illness acceptance, illness helplessness, coping behaviours (of various types) and emotional well-being and physical functioning were tested. This method allows researchers to test the “path” between different variables: the degree to which one variable impacts another and whether this is direct or indirect through a third variable. The results showed both direct and indirect effects of illness acceptance and illness helplessness on the outcome variables of emotional well-being and physical functioning. Lower illness helplessness was related to better emotional well-being and better perceived physical health. This makes sense intuitively: feeling that nothing can be done about poor health is associated with feeling less happy and less able. Additionally, greater acceptance of illness was related directly to greater emotional and physical wellbeing.

Indirect effects were also seen. Greater helplessness was associated with more wishful thinking e.g. “If only I didn’t have this cardiac problem …”, as well as soothing strategies. These coping behaviours were associated with outcomes — more wishful thinking was related to poorer emotional wellbeing and more soothing coping was related to both poorer emotional and physical outcomes. Greater acceptance of illness was associated with less soothing coping and fewer emotional reactions, such as feeling angry. Again, these coping styles were related to the emotional and physical outcomes. This shows the complex nature of the relationships between thoughts, coping behaviours and emotional and physical outcomes.

Through this complex analysis, a simpler summary can be created with direct advice for healthcare: increasing acceptance and decreasing helplessness may improve health outcomes for people with cardiac problems. As with every study, these conclusions must be seen in relation to study limitations. Only subjective or self-reported outcomes of emotion and physical functioning were collected and there can be a large gap between what people report they can do and what they objectively are able to do. It is also vital to note that there were some types of coping that were unrelated to these illness cognitions — adherence to medical advice and “instrumental” coping (problem solving, e.g. locating information, self-management, etc.).

Cardiac disease is a physical illness, however the psychological elements are important to how the illness is experienced. Whilst taking medications, staying active, eating well, avoiding tobacco and alcohol are fundamentally important behaviours that a person should be engaged in, the way people with cardiac disease think is also important. Indeed, screening to identify people with cardiac disease who are showing helplessness and poor acceptance may be useful to select people at further risk. Additionally, interventions to promote healthy thinking as well as healthy behaviours may improve a person’s experience of living with cardiac disease.

References

1. Karademas and Hondronikola. The impact of illness acceptance and helplessness to subjective health, and their stability over time: a prospective study in a sample of cardiac patients. Psychol Health Med. 2010 May;15(3):336-46.
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2. Beaglehole et al. Poverty and human development: the global implications of cardiovascular disease. Circulation. 2007 Oct 23;116(17):1871-3.
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3. Weisfeldt and Zieman. Advances in the prevention and treatment of cardiovascular disease. Health Aff (Millwood). 2007 Jan-Feb;26(1):25-37.
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The study results, reported by NIH scientists at the National Institute of Allergy and Infectious Diseases (NIAID), are similar to findings from two newly reported human cases of the prion disease Gerstmann-Straussler-Scheinker syndrome (GSS). This finding represents a new mechanism of prion disease brain damage, according to study author Bruce Chesebro, M.D., chief of the Laboratory of Persistent Viral Diseases at NIAID’s Rocky Mountain Laboratories.

Prion diseases, also known as transmissible spongiform encephalopathies, primarily damage the brain. Prion diseases include mad cow disease or bovine spongiform encephalopathy in cattle; scrapie in sheep; sporadic Creutzfeldt-Jakob disease (CJD), variant CJD and GSS in humans; and chronic wasting disease in deer, elk and moose.

The role of a specific cell anchor for prion protein is at the crux of the NIAID study. Normal prion protein uses a specific molecule, glycophosphoinositol (GPI), to fasten to host cells in the brain and other organs. In their study, the NIAID scientists genetically removed the GPI anchor from study mice, preventing the prion protein from fastening to cells and thereby enabling it to diffuse freely in the fluid outside the cells.

The scientists then exposed those mice to infectious scrapie and observed them for up to 500 days to see if they became sick. The researchers documented signs typical of prion disease including weight loss, lack of grooming, gait abnormalities and inactivity. But when they examined the brain tissue, they did not observe the sponge-like holes in and around nerve cells typical of prion disease. Instead, the brains contained large accumulations of prion protein plaques trapped outside blood vessels in a disease process known as cerebral amyloid angiopathy, which damages arteries, veins and capillaries in the brain. In addition, the normal pathway by which fluid drains from the brain appeared to be blocked.

Their study, Dr. Chesebro says, indicates that prion diseases can be divided into two groups:

• those with plaques that destroy brain blood vessels
• those without plaques that lead to the sponge-like damage to nerve cells

Dr. Chesebro says the presence or absence of the prion protein anchor appears to determine which form of disease develops.

The new mouse model used in the study and the two new human GSS cases, which also lack the usual prion protein cell anchor, are the first to show that in prion diseases, the plaque-associated damage to blood vessels can occur without the sponge-like damage to the brain. If scientists can find an inhibitor for the new form of prion disease, they might be able to use the same inhibitor to treat similar types of damage in Alzheimer’s disease, Dr. Chesebro says.

Source: NIH News

Statins are a class of drugs that lower cholesterol and thereby reduce the risk of heart disease and stroke. They work by preventing the synthesis of low-density lipoprotein (LDL or “bad cholesterol”) in the liver and promoting its clearance from the blood. They are the most effective cholesterol-lowering drugs currently available and are the cornerstone of the National Heart, Lung, and Blood Institute’s National Cholesterol Education Program (NCEP) treatment guidelines.

The NCEP recommends a “treat-to-target” strategy, in which patients are given specific statin doses to achieve a desired level of LDL cholesterol in the blood. In this case, low LDL cholesterol is the “target.” Yet some physicians are questioning whether treating to any target is the best approach to fighting disease. A recent study in the Annals of Internal Medicine suggests that “tailored treatment”, an approach attempts to practice personalized medicine by estimating three factors, is more effective than a treat-to-target strategy [1].

Researchers examined how a simple tailored treatment compared with a treat-to-target strategy based on NCEP treatment guidelines. They used data from the National Health and Nutrition Examination Survey (conducted from 1988 to 1994) and computationally augmented 4,503 patients between the ages of 30 and 75 who had never been treated with statins and had no history of heart attack to create a simulated population of 1 million. They then estimated each person’s risk for fatal and non-fatal coronary artery disease, and examined the benefits achieved by using a 5-year treatment period. The treat-to-target strategy was based on NCEP guidelines, which includes an optional, more intensive medication regimen (40mg instead of 20mg of simvastatin, a moderate dose-potency statin, and then a potential switch to atorvastatin, a high does-potency statin) for patients at higher risk for coronary artery disease. Both this intensive approach and the standard treat-to-target options were considered In the tailored treatment approach, patients with a 5 — 15% risk of coronary artery disease over 5 years received 40mg simvastatin and those with a risk greater than 15% received 40mg atorvastatin. As in all modeling studies, they made a number of simplifying assumptions: first, that the only thing statins do in the body is reduce LDL cholesterol; and second, that a change in a patient’s LDL cholesterol level is a perfect measure of his or her coronary artery disease risk reduction. The researchers write:

We realize that the first assumption is controversial and that the second assumption is untrue (LDL cholesterol determinations have substantial measurement error), but these assumptions allow us to test the hypothesis that tailored treatment is an inherently superior strategy, even under circumstances most favorable for a treat-to-target strategy.

In calculating the risk factors in their simulated population and analyzing the data from their modeling studies they used a “risk stratified” analysis. This is not how clinical trials are usually analyzed, but it reveals the different benefits and harms accrued by groups of patients with higher and lower risk of disease rather than calculating the average benefit among all of the people in the trial [2]. The researchers found that after five years, tailored treatment prevented significantly more coronary artery disease, saved more lives, treated fewer people overall and treated a smaller percentage of the population with more aggressive treatment. This was the case even with their assumptions biased toward the treat-to-target approach. In their simulated population they identified a group who would receive 40mg simvastatin under tailored treatment but nothing under NCEP guidelines; this group had relatively low LDL levels but high coronary artery disease risk. In contrast, a group who would get 40mg simvastatin under NCEP guidelines but nothing with tailored treatment, had high LDL levels but low overall risk. Tailored treatment could thus spare this patient population unnecessary side effects and expense.

Heart disease, like most complex biological processes, is impacted by a number of factors. These include age, genetics, smoking status, blood pressure and cholesterol levels. None can be considered in isolation. When choosing the best treatment, three things should be considered: the patient’s risk of disease without treatment, the potential benefit of the treatment and the potential harm of the treatment. This study demonstrates that a personalized medicine approach, tailored treatment, provides more benefit per person treated and prevented significantly more coronary artery disease morbidity and death than the currently recommended treat-to-target approaches.

For more information, visit the MedlinePlus interactive tutorial on Managing Cholesterol. The presentation will help you understand what cholesterol is and how to control the level of cholesterol in your body.

References

1. Hayward et al. Optimizing statin treatment for primary prevention of coronary artery disease. Ann Intern Med. 2010 Jan 19;152(2):69-77.
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2. Hayward et al. Reporting clinical trial results to inform providers, payers, and consumers. Health Aff (Millwood). 2005 Nov-Dec;24(6):1571-81.
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3. Cziraky et al. Targeting low HDL-cholesterol to decrease residual cardiovascular risk in the managed care setting. J Manag Care Pharm. 2008 Oct;14(8 Suppl):S3-28; quiz S30-1.
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4. Zulman et al. The relative merits of population-based and targeted prevention strategies. Milbank Q. 2008 Dec;86(4):557-80.
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The difference in the initial level of risk does not appear related to age, based on findings that the increased risk of heart disease was similar between women in their 50s on combination hormone therapy and women in their 60s.

The study is in the Feb. 16, 2010, Annals of Internal Medicine. The WHI is sponsored by the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH).