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Table of Contents
HISTORY OF MEDICINE
Year : 2017  |  Volume : 18  |  Issue : 3  |  Page : 109-114  

Risk factors for coronary artery disease: Historical perspectives

Rachel Hajar
Department of Cardiology, Heart Hospital, Hamad Medical Corporation, Doha, Qatar

Date of Web Publication8-Nov-2017

Correspondence Address:
M.D. Rachel Hajar
Department of Cardiology, Heart Hospital, Hamad Medical Corporation, Doha
Qatar
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/HEARTVIEWS.HEARTVIEWS_106_17

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How to cite this article:
Hajar R. Risk factors for coronary artery disease: Historical perspectives. Heart Views 2017;18:109-14

How to cite this URL:
Hajar R. Risk factors for coronary artery disease: Historical perspectives. Heart Views [serial online] 2017 [cited 2023 Sep 22];18:109-14. Available from: https://www.heartviews.org/text.asp?2017/18/3/109/217850


   Introduction Top


We consider our current understanding and therapy of cardiovascular diseases (CVD) state-of-the-art, but heart disease is still a problem because there is still a lot that we do not know. There is still no cure for any form of heart disease. However, research is ongoing, and new clues are emerging which could lead to better treatments in the future. Results from epidemiological studies, foremost among them the Framingham study, have been crucial to our current knowledge about CVD. Emphasis is on the identification of risk factors, assessment of their predictive ability, and their implications for disease prevention.

The concept of “risk factors” in coronary heart disease (CHD) was first coined by the Framingham heart study (FHS), which published its findings in 1957. FHS demonstrated the epidemiologic relations of cigarette smoking, blood pressure, and cholesterol levels to the incidence of coronary artery disease (CAD). The findings were truly revolutionary for it helped bring about a change in the way medicine is practiced.

Beginnings of our understanding

For thousands of years, our knowledge of the causes of CVD and its therapy was static. It was only in the last half of the 20th century that research into the causes of CVDs accelerated, and with it, new therapies were found.

What stimulated this research? The premature death in 1945 of the US President Franklin D. Roosevelt from hypertensive heart disease and stroke stimulated this research in USA.[1] Deaths from CVD and stroke reached epidemic proportions in the USA at that time which induced the Americans to take the lead in cardiovascular research.

The death of President Roosevelt illustrated how little we knew about the general causes of heart disease and stroke. Therefore, a health project was set up in the USA– the FHS – to identify the common factors or characteristics that contribute to CVD. FHS was under the direction of the National Heart Institute, now known as the National Heart, Lung, and Blood Institute.[2] Researchers followed the development of CHD over a long period in a large group of participants who had not yet developed overt symptoms of CVD or suffered a heart attack or stroke. The small town of Framingham in Massachusetts, USA was chosen due to its geographical proximity to the many cardiologists at Harvard Medical School. Furthermore, the residents had already participated in the Framingham tuberculosis demonstration study two decades earlier.[3]

The town of Framingham is located outside Boston. It was a small, middle-class community, and its small population made it an ideal site to launch the heart study. Everybody knew everyone. It was a typical small-town in the USA. The researchers hoped they would find clues in the medical histories of the people of Framingham which might shed light on causes of CVD. They recruited 5,209 men and women between the ages of 30 and 62 from the town of Framingham, Massachusetts. These study subjects underwent extensive physical examinations and lifestyle interviews that were analyzed for common patterns related to CVD development. Since 1948, the subjects have continued to return to the study every 2 years for a detailed medical history, physical examination, and laboratory tests, and in 1971, the study enrolled a second generation-5,124 of the original participants' adult children, and their spouses to participate in similar examinations.[2] The FHS is now on its third generation of participants. The study has provided substantial insight into the epidemiology of CVD and its risk factors.

Framingham study leads the way

The Framingham study was responsible for pointing out fallacies in our understanding of CVDs and identification of its major risk factors: high blood pressure, high blood cholesterol, smoking, obesity, diabetes, and physical inactivity as well as other valuable information on the effects of related factors such as blood triglyceride and high density lipoprotein (HDL) cholesterol levels, age, gender, and psychosocial issues. To date, no single risk factor has been identified to be responsible for causing CVD; rather, multiple interrelated factors seem responsible for its development. Although the Framingham cohort is Caucasian, other studies have shown that the major risk factors identified in this group apply universally to other racial and ethnic groups.

The notion of CVD risk factors is an integral part of modern medicine which has led to the development of effective treatment and preventive strategies in clinical practice.

Fallacies corrected

Physicians are sometimes taught some theories that are believed to be true without having been proven. These ideas or notions have been doctrines from centuries' old practices. Many of these concepts are taught us in medical school such as the notion that an elevated systolic blood pressure (BP) in the elderly is “normal,” which of course is false as I will discuss later. Then, a study comes along to dispel these erroneous ideas. Such a study was the Framingham heart study. Its epidemiological model of research has unraveled many of the fallacies in our understanding and helped to bring about a change in the way medicine is practiced.

The development of CHD through the prism of its major conventional cardiovascular risk factors – hypertension, hypercholesterolemia, smoking, and diabetes mellitus– is interesting, and hence, I will briefly look at how they evolved as risks through the “eyes” of the FHS and other epidemiological studies.

The major risk factors

There are many risk factors for CAD and some can be controlled but not others. The risk factors that can be controlled (modifiable) are: High BP; high blood cholesterol levels; smoking; diabetes; overweight or obesity; lack of physical activity; unhealthy diet and stress. Those that cannot be controlled (conventional) are: Age (simply getting older increases risk); sex (men are generally at greater risk of coronary artery disease); family history; and race.

Hypertension

Hypertension is one of the risks in the development of CHD. The American President Roosevelt died from cerebral hemorrhage, sequelae of hypertension.

Old myths corrected

Many old physicians thought that high BP was necessary to force blood through the stiffened arteries of older persons and that it was a normal element of aging. The medical community believed that a permissible systolic BP was 100 plus the participant's age in millimeters of mercury.[4],[5] For those aged >70 years, some considered the acceptable upper limits of normal BP to be 210 mmHg systolic and 120 mmHg diastolic.[6]

It was considered appropriate to ignore benign essential hypertension and isolated systolic hypertension. I remember that I was taught in medical school that diastolic pressure was a superior measure of blood pressure. The cardiovascular hazard of hypertension was believed to derive chiefly from the diastolic pressure component. Consequently, elevated systolic pressure was considered harmless, especially in the elderly.[7],[8]

FHS dispelled the concept of “benign essential hypertension.” Belief in the prime importance of the diastolic pressure was convincingly refuted by Framingham study data and later confirmed by other prospectively obtained data demonstrating that the impact of systolic pressure is actually greater than the diastolic component and that even isolated systolic hypertension is dangerous.[9],[10] FHS investigators found an increased risk of CAD morbidity with rising baseline blood pressure. They challenged the existing belief “that systolic pressure is unimportant, and that labile or benign essential hypertension is of little consequence.” They stated that there was “little evidence to support these contentions but considerable reason to doubt them.”[11]

The importance of controlling BP was finally embraced in practice guidelines in the first “Report of the Joint National Committee (JNC) on Detection, Evaluation, and Treatment of High Blood Pressure” in 1977.[12] It is now recognized universally that hypertension increases atherosclerotic CVD incidence; the risk burden is 2–3-fold. CAD is the most common sequelae for hypertensive patients of all ages.[13] Hypertension predisposes to all clinical manifestations of CHD including myocardial infarction, angina pectoris, and sudden death. Even high normal BP values are associated with an increased risk of CVD.[14]

It was thought that the risk ratio for intracerebral hemorrhage was greater than for atherothrombotic brain infarction. This was not true. It was found that hypertension was as strong a risk for atherothrombotic brain infarction as intracerebral hemorrhage.[11]

Framingham showed that the preponderance of hypertension-related strokes were atherothrombotic brain infarctions whether the hypertension was severe or mild. The proportion of strokes due to hemorrhage in mild hypertension was identical to that for severe hypertension.[4]

The Seventh JNC on hypertension established that those with BP of 120–139/80–89 mmHg are prehypertensives, that is, these individuals may become hypertensives in the future. Starting as low as 115/75 mmHg, the risk of heart attack and stroke doubles for every 20-point jump in systolic BP or every 10-point rise in diastolic BP for adults aged 40–70.

The presence of other risk factors for CVD such as high cholesterol, obesity, and diabetes is seen more in people with prehypertension than in those with normal blood pressure. The CVD risk in prehypertensives increases with the number of associated risk factors present. Therefore, prehypertension confers a greater risk for CVD.

In persons with mild to moderate hypertension, the substantial risk was shown to be concentrated in those with coexistent dyslipidemia, diabetes, and left ventricular hypertrophy. Hypertensive elderlies were commonly found to already have target organ damage such as impaired renal function, silent myocardial infarction, strokes, transient ischemic attacks, retinopathy, or peripheral artery disease. At least 60% of older men and 50% of elderly women with hypertension in the Framingham study had one or more of these conditions.[11]

In the past, initiation of antihypertensive treatment was often delayed until there was evidence of target organ involvement. Framingham study data indicated that this practice was unwise because 40%–50% of hypertensive persons developed overt cardiovascular events before evidence of target organ damage such as proteinuria, cardiomegaly, or electrocardiogram abnormalities.[11]

Various guidelines and numerous updates of guidelines on hypertension have been promulgated to improve its treatment and to prevent its adverse cardiovascular consequences. There is no cure for hypertension, but there are helpful pharmacological therapy and some strategies that a person can do to lower risk such as diet and exercise and checking BP regularly.

Hypercholesterolemia

The other major risk for CVD was cholesterol. In 1953, an association between cholesterol levels and CHD mortality was reported in various populations.[15] Animal and clinical observation have suggested such relationship. This association was confirmed by epidemiological studies showing a strong relation between serum total cholesterol and cardiovascular risk.[16],[17],[18]

It was shown that changes in cholesterol levels were associated with changes in CVD incidence rate.[19] Clinicians and epidemiologists accepted these findings, agreeing that total plasma cholesterol was a useful marker for predicting CVD. It was found that its component– the low-density lipoprotein cholesterol (LDL-C) which is the principal lipoprotein transporting cholesterol in the blood, was also directly associated with CVD.[20],[21],[22] It was also found out that LDL cholesterol levels in young adulthood predict development of CVD later in life.[22]

Current guidelines identify LDL-C as the primary target for high blood cholesterol therapy.[23] The benefits of LDL-C lowering drug therapies has been shown in various clinical, observational and experimental studies.[24] It has been shown that the benefits of reducing serum cholesterol for CHD risk are age-related: a 10% reduction in serum cholesterol produces a drop in CHD risk of 50% at the age of 40, 40% at age 50, 30% at age 60, and 20% at age 70.[25]

Now, high density lipoprotein cholesterol (HDL-C) is accepted by the medical community as an important factor in atherosclerosis and consequently, raising HDL-C has become an accepted therapeutic strategy for decreasing CHD incidence rate. There are some drugs that increase HDL-C such as fibrates, niacin, and torcetrapib, a cholesterol ester transfer protein but only fibrates have been shown to reduce risk of major coronary events. It is estimated that a 1 mg/dL increase in HDL level is associated with a decrease in coronary risk of 2% in men and 3% in women.[26]

Smoking

The Framingham study showed that smokers were at increased risk of myocardial infarction (MI) or sudden death and that risk was associated to the number of cigarettes smoked each day.[27] These results were confirmed by other epidemiological studies.[28],[29],[30] The deleterious effect of smoking on health has been proven in many studies, in particular on atherosclerosis.

The harmful effects of smoking on the heart can be appreciated in the following statistics:

  • Cigarette smoking approximately doubles the risk of morbidity and mortality from ischemic heart disease compared with a lifetime of not smoking, and the risk is related to the duration and amount of smoking.[31],[32]
  • There is evidence that in patients with CHD, smoking cessation reduces the risk of all-cause mortality and nonfatal MI.[33] Therefore, all patients with ischemic heart disease should be advised to stop smoking because it is a strong risk factor for a first MI and for fatal and nonfatal recurrences.
  • The risk of morbidity and mortality associated with cigarette smoking falls immediately after stopping smoking, although it may be >20 years, if at all, before the risk associated with smoking is completely reversed.[31],[34]
  • About 20% of patients will give up smoking after an acute MI with resultant 40% reduction in mortality rates and infarct recurrences.[35],[36]
  • For smokers under the age of 50 years the risk of developing CHD is 10 times greater than for nonsmokers of the same age.[37]
  • Passive smoking also increases the risk of CHD.[38]


Diabetes

The role of diabetes in the pathogenesis of CVD was unclear until 1979 when Kannel et al. used data from the Framingham heart study to identify diabetes as a major cardiovascular risk factor. Based on 20 years of surveillance of the Framingham cohort, a two-fold to threefold increased risk of clinical atherosclerotic disease was reported. It was also one of the first studies to demonstrate the higher risk of CVD in women with diabetes compared to men with diabetes.[39] These results have been duplicated by multiple studies. The Kannel article changed the way the medical community thought about diabetes. It is now accepted as a major cardiovascular risk factor. There is a clear-cut relationship between diabetes and CVD. The American Heart association cites the following statistics:[40]

  • At least 68% of people age 65 or older with diabetes die from some form of heart disease; and 16% die of stroke.
  • Adults with diabetes are two to four times more likely to die from heart disease than adults without diabetes.
  • The American Heart association considers diabetes to be one of the seven major controllable risk factors for CVD.


Diabetes is treatable but even if glucose levels are under control it greatly increases the risk of heart disease and stroke because people with diabetes also have other conditions that are risks for developing CHD such as hypertension, smoking, abnormal cholesterol, obesity, lack of physical activity, and metabolic syndrome. The good news is that by managing these risk factors, people with diabetes may avoid or delay the development of CVD.

Physical inactivity

“Conductors on London's double-decker buses (up and down stairs 11 days a fortnight, 50 weeks a year, often for decades) experienced half or less the incidence of acute MI and “sudden death” ascribed to CHD in the sedentary bus drivers.”[41] Thus, began Morris et al. in his landmark article in 1953 which appeared in The Lancet on the association of physical activity and coronary artery disease. Since then a number of epidemiological studies have confirmed the relationship. The relative risk of death from CHD for sedentary compared with active individuals is 1.9 (95% confidence interval).[42] The recommendation of physical exercise has become an important element of preventative policies for the general population (in adults, elderly, and children).

Obesity

The association of obesity and CHD was fist noted by Kannel et al.[43] in Framingham 50 years ago. Obesity is also an independent risk factor for all-cause mortality. It is a metabolic disorder associated with comorbidities such as CHD, type 2 diabetes, hypertension, and sleep apnea. Alterations in metabolic profile and various adaptations in cardiac structure and function occur as excess adipose tissue accumulates.[44] A recent study reported that higher body mass index (BMI) during childhood is associated with an increased risk of CHD in adulthood.[44]

The prevention and control of overweight and obesity in adults and children has become a key element for the prevention of cardiovascular diseases.[45],[46]

Cardiovascular diseases risk assessment

Absolute prediction of CVD risk of a person can be made using prediction charts issued or published by the WHO and ACC/AHA. The recommendations are made for management of major cardiovascular risk factors through changes in lifestyle and prophylactic drug therapies.

The ACC/AHA have produced guidelines for the procedures of detection, management, or prevention of CVD. In November 2013, The ACC and AHA released updated risk-assessment guidelines for atherosclerotic CVD. Changes and recommendations include the following.[47],[48],[49],[50],[51]

  • Stroke is added to the list of coronary events traditionally covered by risk prediction equations.
  • The guidelines focus primarily on the 10-year risk of atherosclerosis-related events; they focus secondarily on the assessment of lifetime risk for adults aged 59 or younger without high shorter-term risk.
  • The strongest predictors of 10-year risk are identified as age, sex, race, total cholesterol, HDL-C, blood pressure, blood-pressure treatment status, diabetes, and current smoking status.
  • Adjunct formulas for refining risk estimates by gender and race are provided.
  • If risk prediction needs to be further sharpened after risk prediction equations have been performed, the guidelines indicate that coronary-artery calcium scores, family history, high-sensitivity C-reactive protein, and the ankle-brachial index can be used.
  • The guidelines recommend that statin therapy be considered in individuals whose 10-year atherosclerotic cardiovascular disease (ASCVD) event risk is 7.5% or greater.


Guidelines from AHA/ACC recommend use of a revised calculator for estimating the 10-year risk of developing a first ASCVD event, which is defined as a nonfatal MI, death from CHD, or stroke (fatal or nonfatal) in a person who was initially free from ASCVD.[51] The calculator incorporates the following risk factors: sex, age, race, total cholesterol, HDL, systolic blood pressure, treatment for elevated blood pressure, diabetes, and smoking.

For patients 20–79 years of age who do not have existing clinical ASCVD, the guidelines recommend assessing clinical risk factors every 4–6 years. For patients with low 10-year risk (<7.5%), the guidelines recommend assessing 30-year or lifetime risk in patients 20–59-year-old.

The guidelines note that regardless of the patient's age, physicians should communicate risk data to the patient and refer to the AHA/ACC lifestyle guidelines, which cover diet and physical activity. For patients with elevated 10-year risk, physicians should communicate risk data and refer to the AHA/ACC guidelines on blood cholesterol and obesity.


   Summary Top


CVD is a major cause of disability and premature death throughout the world. The underlying pathology of atherosclerosis develops over many years and is usually advanced by the time symptoms occur, generally in middle age. The risk of developing CAD increases with age, and includes age >45 years in men and >55 years in women. A family history of early heart disease is also a risk factor, such as heart disease in the father or a brother diagnosed before age 55 years and in the mother or a sister diagnosed before age 65 years. Acute coronary and cerebrovascular events frequently occur suddenly, and are often fatal before medical care can be given. I have discussed above the major traditional risk factors.

Many traditional risk factors for CAD are related to lifestyle, therefore preventative treatment can be tailored to modifying specific factors. It is very important to know these risks to reduce disability and premature deaths from CHD, cerebrovascular disease and peripheral vascular disease in people at high risk, who have not yet experienced a cardiovascular event. People with established CVD are at very high risk of recurrent events.

Current guidelines provide advice on screening and identifying asymptomatic individuals at risk of developing CVD. The objectives of these guidelines are to reduce the incidence of first or recurrent clinical events due to CHD, ischemic stroke, and peripheral artery disease. The focus is on prevention of disability and early death. The guidelines emphasize the importance of lifestyle changes and use of different prophylactic drug therapies in the management of risks.

The understanding of such risk factors is critical to the prevention of cardiovascular morbidities and mortality.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
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[Pubmed] | [DOI]
2 Fatty acid metabolism disorders and potential therapeutic traditional Chinese medicines in cardiovascular diseases
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3 An insight to treat cardiovascular diseases through phytochemicals targeting PPAR-a
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4 Gold Nanoparticles: Synthesis, Functionalization and Biomedical Applications Especially in Cardiovascular Therapy
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5 Effects of Omega-3 Fatty Acids on Flow-mediated Dilatation and Carotid Intima Media Thickness: A Meta-analysis
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6 The association between frailty and incident cardiovascular disease events in community-dwelling healthy older adults
A.R.M. Saifuddin Ekram, Andrew M. Tonkin, Joanne Ryan, Lawrence Beilin, Michael E. Ernst, Sara E. Espinoza, John J. McNeil, Mark R. Nelson, Christopher M. Reid, Anne B. Newman, Robyn L. Woods
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7 The relationship between social isolation, social support, and loneliness with cardiovascular disease and shared risk factors: a narrative review
Achamyeleh Birhanu Teshale, Htet Lin Htun, Jessie Hu, Lachlan L Dalli, Michelle H Lim, Barbara Barbosa Neves, J R Baker, Aung Zaw Zaw Phyo, Christopher M Reid, Joanne Ryan, Alice J Owen, Sharyn M Fitzgerald, Rosanne Freak-Poli
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8 The relationship of circulating neuregulin 4 and irisin, and traditional and novel cardiometabolic risk factors with the risk and severity of coronary artery disease
Elham Alipoor, Mohammad Javad Hosseinzadeh-Attar, Ali Vasheghani-Farahani, Mahnaz Salmani, Mahsa Rezaei, Zahra Namkhah, Monireh Ahmadpanahi, Yaser Jenab, Mohammad Alidoosti, Mehdi Yaseri
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9 Fat fighting liraglutide based nano-formulation to reverse obesity: Design, development and animal trials
Dheeraj Kumar Jakhar, Vishal Kumar Vishwakarma, Raghuraj Singh, Krishna Jadhav, Sadia Shah, Taruna Arora, Rahul Kumar Verma, Harlokesh Narayan Yadav
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10 Competitor induced dissipation of carbon quantum dot based hierarchical vesicular self-assembly: A theranostic nanoplatform towards hypercholesterolemia
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11 Frank's sign associated with the severity of ischemic heart disease in patients under 65 years old
Claudia Elizabeth Velázquez-Sotelo, María José Fernández-Gómez, Annet Cázares-Pérez, Antonio Covarrubias-Gil, Pilar Carranza-Rosales, Irma Edith Carranza-Torres, Javier Morán-Martínez, Nancy Elena Guzmán-Delgado
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12 Treating adult patients of severe psoriasis with methotrexate leads to reduction in biomarkers of atherosclerosis: A prospective study
Shekhar Neema, Biju Vasudevan, Pratibha Misra, Roma Rai, M.K. Sibin, Senkadhir Vendhan, Shantanu Banerjee, Vinay Gera, A.K. Yadav
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13 Genetic data visualization using literature text-based neural networks: Examples associated with myocardial infarction
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14 COVID-19 and coronary artery disease; A systematic review and meta-analysis
Bahareh Hajikhani, Mahshid Safavi, Nazila Bostanshirin, Fatemeh Sameni, Mona Ghazi, Shahrooz Yazdani, Mohammad Javad Nasiri, Nafiseh Khosravi-Dehaghi, Negin Nourisepehr, Saba Sayyari, Masoud Dadashi
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15 The common pathobiology between coronary artery disease and calcific aortic stenosis: Evidence and clinical implications
Toufik Abdul-Rahman, Ileana Lizano-Jubert, Neil Garg, Suprateeka Talukder, Pablo Perez Lopez, Wireko Andrew Awuah, Rohan Shah, Diego Chambergo, Emiliano Cantu-Herrera, Mobeen Farooqi, Nikolaos Pyrpyris, Heloisa de Andrade, Adriana C. Mares, Rahul Gupta, Wesam Aldosoky, Tanveer Mir, Carl J. Lavie, Shady Abohashem
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16 In regard to Milo et al.,
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17 A multicomponent index method to evaluate the relationship between urban environment and CHD prevalence
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18 Organ-specific model of simulated ischemia/reperfusion and hyperglycemia based on engineered heart tissue
J. Pálóczi, Á. Paál, J. Pigler, B. Kiss, A. Rhoden, Z.V. Varga, P. Ferdinandy, T. Eschenhagen, A. Görbe
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19 Cardiovascular risk factors in diabetic patients with and without metabolic syndrome: a study based on the Rafsanjan cohort study
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20 A longitudinal study of the association between attending cultural events and coronary heart disease
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21 Consumption of unprocessed or minimally processed foods and their association with cardiovascular events and cardiometabolic risk factors in Brazilians with established cardiovascular events
Aline Rosignoli da Conceição, Alessandra da Silva, Aline Marcadenti, Ângela Cristine Bersch-Ferreira, Bernardete Weber, Josefina Bressan
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22 CREB-binding protein and HIF-1a/ß-catenin to upregulate miR-322 and alleviate myocardial ischemia-reperfusion injury
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23 Improved bias and reproducibility of coronary artery calcification features using deconvolution
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24 Preventive effect of Helicobacter pylori eradication on the coronary heart diseases depending on age and sex with a median follow-up of 51 months
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25 Insulin-like growth factor 1 reduces coronary atherosclerosis in pigs with familial hypercholesterolemia
Sergiy Sukhanov, Yusuke Higashi, Tadashi Yoshida, Svitlana Danchuk, Mitzi Alfortish, Traci Goodchild, Amy Scarborough, Thomas Sharp, James S. Jenkins, Daniel Garcia, Jan Ivey, Darla L. Tharp, Jeffrey Schumacher, Zach Rozenbaum, Jay K. Kolls, Douglas Bowles, David Lefer, Patrice Delafontaine
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26 Ethnic differences in the lifestyle behaviors and premature coronary artery disease: a multi-center study
Media Babahajiani, Ehsan Zarepur, Alireza Khosravi, Noushin Mohammadifard, Feridoun Noohi, Hasan Alikhasi, Shima Nasirian, Seyed Ali Moezi Bady, Parisa Janjani, Kamal Solati, Masoud Lotfizadeh, Samad Ghaffari, Elmira Javanmardi, Arsalan Salari, Mahboobeh Gholipour, Mostafa Dehghani, Mostafa Cheraghi, Ahmadreza Assareh, Habib Haybar, Seyedeh Mahdieh Namayandeh, Reza Madadi, Javad Kojuri, Marjan Mansourian, Nizal Sarrafzadegan
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27 Thoracic aortic atherosclerosis in patients with a bicuspid aortic valve; a case–control study
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28 Feasibility of a smartphone app for prescribed exercise tutoring in patients with stable coronary heart disease
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29 Association of 25-hydroxyvitamin D levels with lipid profiles in osteoporosis patients: a retrospective cross-sectional study
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30 The prognostic role of the low and very low baseline LDL-C level in outcomes of patients with cardiac revascularization; comparative registry-based cohort design
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31 Association of blood pressure trajectories with coronary heart disease among the disabled population in Shanghai, China: a cohort study of 7 years following up
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32 Evaluation of pericoronary adipose tissue attenuation on CT
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33 Significance of Serum Ferritin and Vitamin-D Level in Coronary Artery Disease Patients
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34 A multivariate genome-wide association study of psycho-cardiometabolic multimorbidity
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35 Association between sociodemographic factors and cholesterol-lowering medication use in U.S. adults post-myocardial infarction
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36 A Review of the Impact of Education on the Adoption of Smart Technologies for Atrial Fibrillation Detection
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37 Relationship between the Castelli risk indeces and the presence and severity of ischemia in non-geriatric patients with suspected coronary artery disease
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38 Predictors of Cardiovascular Morbidity Among Adult Hypertensive Patients: A Cross-Sectional Study from the Kingdom of Saudi Arabia
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39 Risk for acquired coronary artery disease in genetic vs. congenital thoracic aortopathy
Onur B. Dolmaci, Tugay Ayyildiz, Robert E. Poelmann, Antoine H. G. Driessen, Dave R. Koolbergen, Robert J. M. Klautz, Jan H. N. Lindeman, Nimrat Grewal
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40 The association of the paraoxonase 1 Q192R polymorphism with coronary artery disease (CAD) and cardiometabolic risk factors in Iranian patients suspected of CAD
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41 Hypertensive heart disease: risk factors, complications and mechanisms
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42 The relationship between ultra processed food consumption and premature coronary artery disease: Iran premature coronary artery disease study (IPAD)
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43 The Role of Epicardial Adipose Tissue-Derived MicroRNAs in the Regulation of Cardiovascular Disease: A Narrative Review
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44 IgG N-Glycosylation Is Altered in Coronary Artery Disease
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45 Innovative Attention-Based Explainable Feature-Fusion VGG19 Network for Characterising Myocardial Perfusion Imaging SPECT Polar Maps in Patients with Suspected Coronary Artery Disease
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46 Comparison of Genetic Susceptibility to Coronary Heart Disease in the Hungarian Populations: Risk Prediction Models for Coronary Heart Disease
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47 Is It Feasible to Predict Cardiovascular Risk among Healthy Vegans, Lacto-/Ovo-Vegetarians, Pescatarians, and Omnivores under Forty?
Izabela Kwiatkowska, Jakub Olszak, Alicja Brozek, Anna Blacha, Marcin Nowicki, Kalina Mackowiak, Piotr Formanowicz, Dorota Formanowicz
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48 Role of Terpenophenolics in Modulating Inflammation and Apoptosis in Cardiovascular Diseases: A Review
Muhamad Adib Abdul Ghani, Azizah Ugusman, Jalifah Latip, Satirah Zainalabidin
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49 Role of the Gut Microbiome in the Development of Atherosclerotic Cardiovascular Disease
Ahmad Al Samarraie, Maxime Pichette, Guy Rousseau
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50 C-Reactive Protein Levels and Risk of Cardiovascular Diseases: A Two-Sample Bidirectional Mendelian Randomization Study
Annapurna Kuppa, Himi Tripathi, Ahmed Al-Darraji, Wadea M. Tarhuni, Ahmed Abdel-Latif
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51 Presence of trans-Fatty Acids Containing Ingredients in Pre-Packaged Foods and the Availability of Reported trans-Fat Levels in Kenya and Nigeria
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52 How Do Minerals, Vitamins, and Intestinal Microbiota Affect the Development and Progression of Heart Disease in Adult and Pediatric Patients?
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53 Prediction of obstructive coronary artery disease in patients undergoing heart valve surgery: A cross-sectional study in a tertiary care hospital
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54 Ejercicio: la medicina menos valorada y utilizada
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55 Association between the Phytochemical Index and Risk Factors for Cardiovascular Disease in Adults
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56 The Correlation between High Sensitive C-reactive Protein Levels and Gensini Score in Diabetes Patients
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57 Recent advances in diagnosis and management of ischemic heart diseases in perspective of contemporary and Ayurveda medicine—a comprehensive review
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58 Automated Cardiovascular Disease Prediction Models: A Comparative Analysis
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59 Patterns of Coronary Artery Dominance and Association with Severity of Coronary Artery Disease at a Large Tertiary Care Hospital in Pakistan
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60 Atypical Presentations of Myocardial Infarction: A Systematic Review of Case Reports
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61 First Successful Human Coronary Artery Bypass Surgery Postoperative Heart Transplant: A Case Report
Sam Zeraatian Nejad, Mohammadhosein Akhlaghpasand, Ida Mohammadi, Kiarash Soltani, Foolad Eghbali
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62 Acute coronary syndrome: role of the nurse in patient assessment and management
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63 Assessment of Right Ventricular Function in Patients With Acute Myocardial Infarction
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64 Incidence of Coronary Artery Disease in King Abdulaziz University Hospital, Jeddah, Saudi Arabia, 2019–2020: A Retrospective Cohort Study
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65 Awareness of Coronary Artery Disease Risk Factors Among the Population of Taif City, Saudi Arabia
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66 Correlation of Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers with serum GDF-15 in a group of hypertensive Iraqi patients
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67 Knowledge, Attitude, and Practice Toward Cardiovascular Diseases in the Lebanese Population
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68 Predictors of Coronary Heart Disease (CHD) among Malaysian Adults: Findings from MyDiet-CHD Study
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69 Atherogenic Index of Plasma and Its Association with Risk Factors of Coronary Artery Disease and Nutrient Intake in Korean Adult Men: The 2013–2014 KNHANES
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70 The use of screening tools for cardiovascular risk assessment in psoriasis – A case- control study
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71 PCSK9 Promotes Cardiovascular Diseases: Recent Evidence about Its Association with Platelet Activation-Induced Myocardial Infarction
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72 Clinical Significance of Monocyte Chemoattractant Protein-1 and CC Chemokine Receptor Type 2 Gene Polymorphisms in Young Patients with Acute Coronary Syndrome
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73 Vital Signs Monitoring Based on Interferometric Fiber Optic Sensors
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74 Clinical Patterns of Traditional Chinese Medicine for Ischemic Heart Disease Treatment: A Population-Based Cohort Study
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75 Why Do High-Risk Patients Develop or Not Develop Coronary Artery Disease? Metabolic Insights from the CAPIRE Study
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76 Untargeted Metabolomics Profiling Reveals Perturbations in Arginine-NO Metabolism in Middle Eastern Patients with Coronary Heart Disease
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77 Sex Differences in Baseline Characteristics Do Not Predict Early Outcomes after Percutaneous Coronary Intervention: Results from the Australian GenesisCare Cardiovascular Outcomes Registry (GCOR)
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78 Influence of Risk Factors on Exercise Tolerance in Patients after Myocardial Infarction—Early Cardiac Rehabilitation in Poland
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79 Are Thoracic Aortic Aneurysm Patients at Increased Risk for Cardiovascular Diseases?
Onur B. Dolmaci, Sulayman El Mathari, Antoine H. G. Driessen, Robert J. M. Klautz, Robert E. Poelmann, Jan H. N. Lindeman, Nimrat Grewal
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80 Bone Health in Patients with Dyslipidemias: An Underestimated Aspect
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81 Aging of Vascular System Is a Complex Process: The Cornerstone Mechanisms
Anastasia V. Poznyak, Nikolay K. Sadykhov, Andrey G. Kartuesov, Evgeny E. Borisov, Vasily N. Sukhorukov, Alexander N. Orekhov
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82 From Diabetes to Atherosclerosis: Potential of Metformin for Management of Cardiovascular Disease
Anastasia V. Poznyak, Larisa Litvinova, Paolo Poggio, Donato Moschetta, Vasily Nikolaevich Sukhorukov, Alexander N. Orekhov
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83 Apolipoprotein E in Cardiometabolic and Neurological Health and Diseases
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84 The New Markers of Early Obesity-Related Organ and Metabolic Abnormalities
Agata Ziomber-Lisiak, Kaja Piana, Beata Ostachowicz, Pawel Wróbel, Paula Kasprzyk, Jolanta Kaszuba-Zwoinska, Agnieszka Baranowska-Chowaniec, Kajetan Juszczak, Magdalena Szczerbowska-Boruchowska
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85 Handgrip Strength-Related Factors in a Colombian Hypertensive Population: A Cross-Sectional Study
Yulieth Rivas-Campo, Elsa Patricia Muñoz-Laverde, Agustín Aibar-Almazán, José Daniel Jiménez-García, Antonio Martínez-Amat, Patricia Alexandra García-Garro, Juan Miguel Muñoz-Perete, Manuel Garcia-Sillero, Yolanda Castellote-Caballero
International Journal of Environmental Research and Public Health. 2022; 19(6): 3726
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86 Religiosity Is Associated with Reduced Risk of All-Cause and Coronary Heart Disease Mortality among Jewish Men
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International Journal of Environmental Research and Public Health. 2022; 19(19): 12607
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87 The Role of Fatty Acid Binding Protein 3 in Cardiovascular Diseases
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88 Occupational Exposure to Poorly Soluble Low Toxicity Particles and Cardiac Disease: A Look at Carbon Black and Titanium Dioxide
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89 Lycopene: A Natural Arsenal in the War against Oxidative Stress and Cardiovascular Diseases
May Nasser Bin-Jumah, Muhammad Shahid Nadeem, Sadaf Jamal Gilani, Bismillah Mubeen, Inam Ullah, Sami I. Alzarea, Mohammed M. Ghoneim, Sultan Alshehri, Fahad A. Al-Abbasi, Imran Kazmi
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90 The Association of Preoperative Depression, and C-Reactive Protein Levels with a Postoperative Length of Stay in Patients Undergoing Coronary Artery Bypass Grafting
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91 Elucidating the relationship between dyslipidemia and osteoporosis: A multicenter, prospective cohort study protocol
Xu Wei, Yili Zhang, Chuanrui Sun, Baoyu Qi, Xinyi Huang, Ming Chen, Ning Liu, Kai Sun, Xin Chen, Xiaokuan Qin, Yanming Xie, Liguo Zhu
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92 Rs420137, rs386360 and rs7763726 polymorphisms in fibronectin type III domain containing 1 are associated with susceptibility to coronary heart disease: Analysis in the Han population
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93 Correlation between chronic inflammation of rheumatoid arthritis and coronary lesions: “About a monocentric series of 202 cases”
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94 Differences in the number of stented coronary arteries based on the seven traditional obesity parameters among patients with coronary artery diseases undergoing cardiac catheterization
Audai A Hayajneh, Islam M Alhusban, Mohammad Rababa, Sami Al-Rawashdeh, Shatha Al-Sabbah, Dania Bani-Hamad
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95 Neuropsychological tests and prediction of dementia in association with the degree of carotid stenosis
Ondrej Machaczka, David Školoudík, Jana Janoutová, Martin Roubec, Eva Reiterová, Martina Kovalová, Anna Zatloukalová, Petr Ambroz, Vladimír Janout
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96 Effectiveness of a Nurse-Led Support Programme Using a Mobile Application versus Phone Advice on Patients at Risk of Coronary Heart Disease – A Pilot Randomized Controlled Trial
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97 Hemp Seeds, Flaxseed, and Açaí Berries: Health Benefits and Nutritional Importance with Emphasis on the Lipid Content
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98 Genetic variations of renin-angiotensin and fibrinolytic systems and susceptibility to coronary artery disease: a population genetics perspective
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99 Pooled prevalence of three major cardiovascular risk factors in patients undergoing left main bifurcation stenting: a systematic review and meta-analysis
Gianluca RIGATELLI, Marco ZUIN, Dobrin VASSILEV, Alberto MAZZA, Claudio BILATO, Loris RONCON
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100 Pathophysiological and clinical aspects of the circadian rhythm of arterial stiffness in diabetes mellitus: A minireview
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101 Variations in coronary artery diameter: a retrospective observational study in Indian population
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102 Familial hypercholesterolaemia and coronary risk factors among patients with angiogram-proven premature coronary artery disease in an Asian cohort
Sukma Azureen Nazli, Yung-An Chua, Noor Alicezah Mohd Kasim, Zaliha Ismail, Ahmad Bakhtiar Md Radzi, Khairul Shafiq Ibrahim, Sazzli Shahlan Kasim, Azhari Rosman, Hapizah Nawawi, Xiao-Feng Yang
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103 Coronary Artery Disease in Patients Undergoing Transvalvular Aortic Valve Implantation
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104 Knowledge of modifiable cardiovascular diseases risk factors and its primary prevention practices among diabetic patients at Jimma University Medical Centre: A cross-sectional study
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105 Inequalities in the prevalence of cardiovascular disease risk factors in Brazilian slum populations: A cross-sectional study
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106 Improving physical and psychological outcomes of cardiac patients using the Naluri app: A study protocol for a randomized controlled trial
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107 Vegetarian ethnic foods of South India: review on the influence of traditional knowledge
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108 The effects of olive leaf extract on cardiovascular risk factors in the general adult population: a systematic review and meta-analysis of randomized controlled trials
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109 Relationship between active Helicobacter pylori infection and risk factors of cardiovascular diseases, a cross-sectional hospital-based study in a Sub-Saharan setting
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110 Triglyceride glucose index for the detection of the severity of coronary artery disease in different glucose metabolic states in patients with coronary heart disease: a RCSCD-TCM study in China
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111 Unsupervised machine learning based on clinical factors for the detection of coronary artery atherosclerosis in type 2 diabetes mellitus
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112 Chrysin reduces hypercholesterolemia-mediated atherosclerosis through modulating oxidative stress, microflora, and apoptosis in experimental rats
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113 The Impact of Accelerated Diagnostic Protocol Implementation on Chest Pain Observation Unit Utilization
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114 Risk assessment indicators and brachial-ankle pulse wave velocity to predict atherosclerotic cardiovascular disease
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115 A urinary peptidomics approach for early stages of cardiovascular disease risk: The African-PREDICT study
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116 Inequity in exercise-based interventions for adults with rheumatoid arthritis: a systematic review
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117 Why binge television viewing can be bad for you
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118 Living donor liver transplantation in a cohort of recipients with left ventricular systolic dysfunction
Pooja Bhangui, Prashant Bhangui, Manish Aneja, Nishant Sharma, Nikunj Gupta, A.S. Soin, Vijay Vohra
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119 Increased risk of coronary heart disease with hysterectomy in young women: A longitudinal follow-up study using a national health screening cohort
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120 Effect of losartan potassium, metformin hydrochloride, and simvastatin on in vitro bioaccessibility of Cu, Fe, Mn, and Zn in oat flour from Brazil
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121 Role of miRNA-27a and miRNA-224 in posttranscriptional regulation of PCSK9 gene in Iraqi patient with coronary artery disease
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122 Longitudinal effects of lipid indices on incident cardiovascular diseases adjusting for time-varying confounding using marginal structural models: 25 years follow-up of two US cohort studies
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123 The efficacy of Zingiber officinale on dyslipidaemia, blood pressure, and inflammation as cardiovascular risk factors: A systematic review
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124 Complications of Vascular Disease
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125 Role of Sex in Atherosclerosis: Does Sex Matter?
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126 Contraception for Adolescents and Young Women with Type 2 Diabetes–Specific Considerations
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127 Coronary Artery Disease and Aspirin Intolerance: Background and Insights on Current Management
Ravi A. Thakker, Leonardo Salazar, Deaa Abu Jazar, Pooja Bhakta, Bryan Baker, Chandani Patel, Ayman Elbadawi, Mayank Agarwal, Aiham Albaeni, Mohammed Saleh, Jonathan Esclovan, Danielle El Haddad, Hashim Alwash, Ankur Kalra, Sachin S. Goel, Robert Jay Widmer, Khaled Chatila, Wissam Khalife, Afaq Motiwala, Jennifer McCracken, Hani Jneid, Syed Gilani
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128 Forensic autopsy-confirmed thrombosis-related deaths: the danger in the bones
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129 Daytime napping and coronary heart disease risk in adults: a systematic review and dose–response meta-analysis
Nader Salari, Sajjad Moradi, Reza Bagheri, Sepide Talebi, Alexei Wong, Basir Babavaisi, Mohammad ali Hojjati Kermani, Niloofar Hemati
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130 The correlation of long non-coding RNAs IFNG-AS1 and ZEB2-AS1 with IFN-? and ZEB-2 expression in PBMCs and clinical features of patients with coronary artery disease
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132 Commercial pure titanium – A potential candidate for cardiovascular stent
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133 Effects of intervention on lifestyle changes among coronary artery disease patients: A 6-month follow-up study
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134 Phytotherapy with active tea constituents: a review
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135 Chrysin attenuates high-fat-diet-induced myocardial oxidative stress via upregulating eNOS and Nrf2 target genes in rats
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136 Uncurtaining the pivotal role of ABC transporters in diabetes mellitus
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137 Association between satellite-based estimates of long-term PM2.5 exposure and cardiovascular disease: evidence from the Indonesian Family Life Survey
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140 The effectiveness of planned discharge education on health knowledge and beliefs in patients with acute myocardial infarction: a randomized controlled trial
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141 Strengthening the Case for Cluster Set Resistance Training in Aged and Clinical Settings: Emerging Evidence, Proposed Benefits and Suggestions
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143 Cannabis Use and Electrocardiographic Myocardial Injury
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144 Convolutional and recurrent neural networks for the detection of valvular heart diseases in phonocardiogram recordings
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145 Investigation of climate change impacts on long-term care facility occupants
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146 A Meta-Analysis on the Global Prevalence, Risk factors and Screening of Coronary Heart Disease in Nonalcoholic Fatty Liver Disease
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149 Evaluation of ERRFI1 +808 T/G variant and its mRNA expression in coronary artery in-stent restenosis
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150 Outbreak of SARS-CoV2: Pathogenesis of infection and cardiovascular involvement
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151 The global prevalence of Chlamydia pneumoniae, Helicobacter pylori, Cytomegalovirus and Herpes simplex virus in patients with coronary artery disease: A systematic review and meta-analysis
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152 Effects of guar gum supplementation on the lipid profile: A systematic review and meta-analysis of randomized controlled trials
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153 Examining Acute Coronary Syndrome Across Ethnicity, Sex, and Age
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155 Ultra-processed foods consumption is associated with cardiovascular disease and cardiometabolic risk factors in Brazilians with established cardiovascular events
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156 Unmet Medical Need as a Driver for Pharmaceutical Sciences – A Survey Among Scientists
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157 In silico investigation on alkaloids of Rauwolfia serpentina as potential inhibitors of 3-hydroxy-3-methyl-glutaryl-CoA reductase
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158 Modelling the spread of atherosclerosis considering relapse and linear treatment
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159 A Numerical Analysis of Blood Flow in Clogged Artery
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160 The Degradation of G3BP2 by Trim-away Method Inhibits Oscillatory Shear Stress induced Endothelial Cell Inflammation
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162 An evaluation of lipid profile and pro-inflammatory cytokines as determinants of cardiovascular disease in those with diabetes: a study on a Mexican American cohort
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163 Contribution of lncRNA CASC8, CASC11, and PVT1 Genetic Variants to the Susceptibility of Coronary Heart Disease
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166 Coronary calcification is associated with elevated serum lipoprotein (a) levels in asymptomatic men over the age of 45 years
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168 Adherence to guideline-recommended HbA1c testing frequency and better outcomes in patients with type 2 diabetes: a 5-year retrospective cohort study in Australian general practice
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169 Relative Impact of Clinical Risk Versus Procedural Risk on Clinical Outcomes After Percutaneous Coronary Intervention
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170 Supporting Real World Decision Making in Coronary Diseases Using Machine Learning
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