Genesis of Statins

2009 ◽  
Author(s):  
Jie Jack Li
Keyword(s):  
Heart Disease ◽  
Thyroid Hormone ◽  
Large Scale ◽  
Hormone Treatment ◽  
Blood Cholesterol ◽  
Heart Attacks ◽  
Cholesterol Levels ◽  
The 1950S ◽  
Loss Of Libido ◽  
Artery Disease

As evidence grew that high blood cholesterol levels were linked to heart disease, scientists in both academia and industry began to look for drugs to lower cholesterol as early as the 1950s. Before Akira Endo discovered the first statin, mevastatin, in the 1970s, many things, including hormones, vitamins, and resins, were tried to lower cholesterol. Some worked, and some did not. Thyroid hormone was one of the fi st drugs used for that purpose. The cholesterol-lowering properties of dextro-thyroxine were discovered by serendipity. At one point, surgical removal of part of the thyroid gland had been used to relieve angina, the pain brought on by exercise in coronary artery disease. Doctors observed that thyroid removal also raised the blood cholesterol level, which in turn sped up arterial degeneration. By deduction, the doctors reasoned that taking thyroid hormone should then decrease blood cholesterol levels. Initial clinical trials proved this theory, and dextro-thyroxine was used to lower cholesterol beginning in the 1950s, when thyroid extract became a standard treatment for hypercholesterolemic (high cholesterol) patients. Unfortunately, too much thyroid hormone made patients tremble all the time. Later, a large-scale, long-term clinical trial named the “Coronary Drug Project” established the association of dextro-thyroxine with ischemic heart disease as a severe side eff ect in men. As a consequence, thyroid hormone treatment was discontinued. Women, in contrast to men, enjoy natural cardiac protection through the action of the female sex hormones, the estrogens. In 1930, a minute quantity of estrogen was isolated from the ovaries of 80,000 sows. In the 1950s, reports appeared that estrogen could lower blood cholesterol levels even more effectively than nicotinic acid, another anticholesterol drug used at the time. Unfortunately, men on estrogen for too long began to develop feminine traits, including breast enlargement and loss of libido, and other side effects, although they did acquire relative immunity from heart attacks until late in life. Due to the lack of safe and effiicacious drugs, some doctors seemed willing to take their chances with estrogens.

Risk Factors for Coronary Artery Disease in Children: Recognition, Evaluation, and Therapy

1980 ◽  
Vol 2 (5) ◽  
pp. 131-138
Author(s):  
C. J. Glueck ◽  
M. J. Mellies ◽  
R. C. Tsang ◽  
J. A. Morrison
Keyword(s):  
Risk Factors ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Eating Habits ◽  
Plasma Cholesterol ◽  
Saturated Fat ◽  
Cholesterol Levels ◽  
Chd Risk ◽  
Artery Disease ◽  
Atherosclerosis Prevention

PEDIATRIC GENESIS OF ATHEROSCLEROSIS Atherosclerosis results from a variety of pathophysiologic disturbances, some currently recognized, and many undoubtedly not yet recognized, which in aggregate are identified as risk factors. Genetic and environmental influences conjointly affect the incidence and the severity of these risk factors and, thus, coronary heart disease (CHD) risk. Prophylaxis should be designed to prevent or retard the development of arterial plaques. This suggests that diagnostic and preventive efforts should begin in childhood. Eating habits are also probably established in childhood, allowing their early modification. The atherosclerotic plaque appears to have its genesis in childhood. The data from wartime autopsies confirm the presence of mature atherosclerotic lesions by the end of the second decade and emphasize the importance of primary atherosclerosis prevention beginning in the first and second decades. While there are clearly genetic factors in CHD, variation in rates in differing geographic areas appears less likely to be related to genetic than to environmental differences. Marked differences in plasma cholesterol levels are found in children in different geographic areas, generally paralleling pediatric cholesterol and saturated fat intake and the incidence of adult coronary heart disease. The relationships of elevated total plasma cholesterol levels to the incidence of coronary heart disease are clearly established in adults.

Treatment with Simvastatin and Low-dose Aspirin Depresses Thrombin Generation in Patients with Coronary Heart Disease and Borderline-high Cholesterol Levels

2001 ◽  
Vol 85 (02) ◽  
pp. 221-225 ◽  
Author(s):  
Anetta Undas ◽  
Robert Undas ◽  
Jan Brożek ◽  
Andrzej Szczeklik ◽  
Jacek Musiał
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Thrombin Generation ◽  
Low Dose ◽  
Ex Vivo ◽  
Blood Cholesterol ◽  
High Cholesterol ◽  
Cholesterol Levels ◽  
Dose Aspirin ◽  
Low Dose Aspirin

SummaryAspirin and statins are beneficial in coronary heart disease across a broad range of cholesterol levels. We assessed the effects of low-dose aspirin (75 mg daily) on thrombin generation in patients with coronary heart disease and average blood cholesterol levels. We also investigated whether in patients with borderline-high cholesterol level who have been already taking aspirin, additional treatment with simvastatin would affect thrombin generation.Seven-day treatment with low-dose aspirin decreased thrombin generation ex vivo only in patients with total cholesterol 5.2 mmol/L. In patients with higher cholesterol levels aspirin had no effect. In these patients, already taking low-dose aspirin, additional three-month simvastatin treatment resulted in a reduction of thrombin generation. This demonstrates that low-dose aspirin depresses thrombin generation only in subjects with desirable blood cholesterol levels, while in others, with borderline-high cholesterol, thrombin formation is being reduced following the addition of simvastatin.

Drug Treatment in the Prevention of Coronary Artery Disease

1979 ◽  
Author(s):  
J.R.A. Mitchell
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Heart Disease ◽  
Clinical Trials ◽  
Heart Disease ◽  
Major Part ◽  
Large Scale ◽  
End Points ◽  
Pump Failure ◽  
Artery Disease

The disappointing performance of anticoagulants in the prophylaxis of coronary heart disease led to the realisation that components other than fibrin play a major part in the structure of arterial thrombi. Attention has therefore been focussed on the possible role of agents which modify platelet behaviour. Novel agents which alter thromboxane synthesis will not be available for large-scale clinical trials for some years, so the present trials are assessing the value of platelet-modifying agents which are already in use for other purposes. The implications of the Antura-Reinfarction study and the role of aspirin and persantin will be discussed.Attention will also be drawn to the importance of using valid end-points to assess potential anti-thrombotic regimes in coronary disease. The differential implications of using infarction, sudden death, pump failure, dysrhythmias and re-infarction as end-points in trials will be described.

scholarly journals Novel RNAi-Based Therapies for Atherosclerosis

2021 ◽  
Vol 23 (8) ◽  
Author(s):  
Anna-Kaisa Ruotsalainen ◽  
Petri Mäkinen ◽  
Seppo Ylä-Herttuala
Keyword(s):  
Plasma Cholesterol ◽  
Common Factor ◽  
New Drugs ◽  
Blood Cholesterol ◽  
Advanced Treatment ◽  
Cell Debris ◽  
Cholesterol Levels ◽  
Atherosclerosis Risk ◽  
Artery Disease ◽  
Atherosclerosis Risk Factors

Abstract Purpose of Review Atherosclerosis, defined by inflammation and accumulation of cholesterol, extracellular matrix, and cell debris into the arteries is a common factor behind cardiovascular diseases (CVD), such as coronary artery disease, peripheral artery disease, and stroke. In this review, we discuss and describe novel RNA interference (RNAi)-based therapies in clinical trials and on the market. Recent Findings The first RNAi-based therapies have entered clinical use for the control of atherosclerosis risk factors, i.e., blood cholesterol levels. The most advanced treatment is silencing of proprotein convertase subtilisin/kexin type 9 (PCSK9) with a drug called inclisiran, which has been approved for the treatment of hypercholesterolemia in late 2020, and results in a robust decrease in plasma cholesterol levels. Summary As the new RNAi therapies for atherosclerosis are now entering markets, the usefulness of these therapies will be further evaluated in larger patient cohorts. Thus, it remains to be seen how fast, effectively and eminently these new drugs consolidate their niche within the cardiovascular disease drug palette.

HEART DISEASE-IS DIET A FACTOR?1

1972 ◽  
Vol 35 (6) ◽  
pp. 340-348 ◽  
Author(s):  
H. D. Hurt
Keyword(s):  
Fatty Acids ◽  
Heart Disease ◽  
Eating Habits ◽  
Saturated Fatty Acids ◽  
Animal Experiments ◽  
Indirect Evidence ◽  
Blood Cholesterol ◽  
Cholesterol Levels ◽  
Apparent Relationship ◽  
Optimal Health

Data derived from extensive population surveys and animal experiments have provided indirect evidence associating elevated blood cholesterol levels with the increased incidences of atherosclerotic heart disease. As a result of this apparent relationship, recommendations have been made regarding the kind and amount of fatty acids and cholesterol which should be consumed for optimal health. Before massive changes are made in the eating habits of our population, the actual causal relationship between dietary fat and cholesterol to subsequent blood cholesterol levels and atherosclerotic heart disease should be determined. Although several risk factors have been characterized which will possibly aid in identification of those individuals most prone to development of atherosclerotic heart disease, the potential benefit from reducing a single risk factor in the prevention of the disease has not yet been conclusively demonstrated. The relative importance of dairy products as contributors of dietary saturated fatty acids and cholesterol is discussed in relationship to their association to heart disease.

scholarly journals Premature Coronary Artery Disease and Familial Hypercholesterolemia: Need for Early Diagnosis and Cascade Screening in the Indian Population

2012 ◽  
Vol 2012 ◽  
pp. 1-4 ◽  
Author(s):  
N. Setia ◽  
I. C. Verma ◽  
B. Khan ◽  
A. Arora
Keyword(s):  
Heart Disease ◽  
Familial Hypercholesterolemia ◽  
Genetic Factors ◽  
Age Of Onset ◽  
Ldl Receptor ◽  
Premature Coronary Artery Disease ◽  
Cascade Screening ◽  
Cholesterol Levels ◽  
Premature Cad ◽  
Artery Disease

Cardiovascular disease (CVD) is the leading cause of death in India, accounting for 28% of mortality. The average age of onset of CVD is younger (below 55 years) among Indians than in other populations. This may be due to bad lifestyle, genetic factors, or both. Hypertension, smoking, diabetes, and physical inactivity have been identified as modifiable risk factors for heart disease. Hypercholesterolemia is the most common and treatable cause of heart disease. Genetic factors that lead to hypercholesterolemia have not been fully studied in India. Familial Hypercholesterolemia results from mutations in the LDL receptor, ApoB, PCSK9, and ApoE genes. There is an urgent need to screen subjects with premature CAD and their relatives in India for the presence of FH, identify the mutations that lead to high cholesterol, and carry out cascade screening in the at-risk relatives. Those harbouring mutations in the above genes can be treated to lower the cholesterol levels, prevent early CVD, and avoid death. A programme based on these lines has been initiated in Delhi.

scholarly journals Cholesterol Screening in Children and Family History of Coronary Heart Disease.

Circulation ◽  
2001 ◽  
Vol 103 (suppl_1) ◽  
pp. 1369-1369
Author(s):  
Viktorina N Muratova ◽  
Syed S Islam ◽  
Emily C Spangler ◽  
Ellen W Demerath ◽  
William A Neal
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Family History ◽  
Lipid Profile ◽  
School Children ◽  
Preventive Health Care ◽  
Blood Cholesterol ◽  
Cholesterol Screening ◽  
Cholesterol Levels ◽  
History Of

P94 Background: Selective blood cholesterol screening of children based upon National Cholesterol Education Program (NCEP) guidelines of family history of premature cardiovascular disease (CVD) or parental hypercholesterolemia is inadequate in a population with high prevalence of coronary heart disease (CHD), low levels of cholesterol screening, low socio-economic status (SES) and diminished access to preventive health care. We hypothesize that universal cholesterol screening of pre-pubertal school children may be effective in identifying children and their parents with abnormal lipid levels in this high risk rural population. Fifth grade school children from seven rural Appalachian counties participated in a school based cholesterol screening program. Data on family history of premature CHD, anthropometric and blood pressure measurements, tobacco smoke exposure, dietary history and physical activity levels were collected at the time of screening. Seven hundred and nine 5 th grade students ( mean age 10.8 years) participated in the program. One hundred seventy four (24.5%) were considered presumptively dyslipidemic after non-fasting finger- stick (FS) cholesterol screening. Thirty six percent of these dyslipidemic children had a fasting lipid profile done. Dyslipidemia was confirmed in 37(59%) of these children. FS cholesterol levels were significantly correlated with fasting TC (r=0.80 p < 0.0001). Among confirmed dyslipidemic children, family history was not a good predictor of dyslipidemia (sensitivity 21.6%). Seventy nine parents of dyslipidemic children participated in fasting lipid profile assessment. Fifty two parents (67%) were dyslipidemic, most of them (79%) did not have a family history of premature CHD or hypercholesterolemia. FS cholesterol levels were also correlated with fasting TC of fathers (r=0.46 p=0.01), and mothers (r=0.32 p=0.02). Conclusion: Significant correlation exists between non-fasting FS cholesterol levels of children and subsequent fasting lipid profile of children and their parents. Family history has low sensitivity in predicting children with elevated serum cholesterol concentrations.

scholarly journals Novel uses of thyroid hormones in cardiovascular conditions

Endocrine ◽  
2019 ◽  
Vol 66 (1) ◽  
pp. 115-123 ◽  
Author(s):  
Salman Razvi
Keyword(s):  
Cardiovascular Diseases ◽  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Hormone Therapy ◽  
Large Scale ◽  
Experimental Studies ◽  
Hormone Treatment ◽  
Limited Data ◽  
Hormone Levels ◽  
Thyroid Hormone Levels

Abstract Thyroid hormone levels are reduced in cardiovascular diseases and this phenomenon is associated with worse outcomes. It is unclear whether the changes in thyroid hormone bioavailability to the affected myocardium are beneficial or if this is a maladaptive response. Experimental studies from animal models of acute myocardial infarction (AMI) suggest that thyroid hormone treatment may be beneficial. There is limited data available on the use of thyroid hormones in patients with AMI and heart failure and this suggests that treatment to normalise thyroid hormone levels may be safe and potentially efficacious. Similarly, evidence of thyroid hormone therapy in patients undergoing cardiac surgery or during cardiac transplantation is limited. It is therefore difficult to draw any firm conclusions about benefits or risks of thyroid hormone treatment in these conditions. Large scale clinical trials of thyroid hormones in patients with cardiac conditions are required to confirm safety and evaluate efficacy. Furthermore, it needs to be elucidated which hormone to administer (thyroxine or triiodothyronine), when in the disease pathway to treat, dose of thyroid hormone to administer, and which parameters to utilise to assess safety and efficacy. Until these important questions are answered thyroid hormone therapy in cardiovascular diseases must remain within the research domain.

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