Wilu's paper: chapter 4, The correlation between cholesterol and CHD

CHAPTER 4 THE CORRELATION BETWEEN CHOLESTEROL AND CORONARY HEART DISEASE 4.1 The correlations between cholesterol and coronary heart disease Coronary heart disease is usually caused by a condition called atherosclerosis, which occurs when fatty material and a substance called plaque builds up on the walls of your arteries. This causes them to get narrow. As the coronary arteries narrow, blood flow to the heart can slow down or stop, causing chest pain (stable angina), shortness of breath, heart attack, and other symptoms.Plaque is like a firm shell with a soft inner core containing cholesterol. As blood hits it during each heartbeat, the plaque may crack open and expose its inner cholesterol core, which promotes blood clotting. Clots may further reduce blood flow, causing severe pain (angina), or even block it all together. Despite the declining coronary heart disease (CHD) mortality rate, Coronary Heart Disease remains a major cause of premature death and imposes high personal, social and economic costs. Blood cholesterol is an important risk factor for Coronary heart disease but should be considered in the context of other risk factors such as smoking, raised blood pressure and physical inactivity. Blood cholesterol alone is a relatively poor predictor of individual Coronary Heart Disease risk. The majority of Coronary Heart Disease events occur in people with average or low blood cholesterol levels. Cholesterol lowering using statins is effective at reducing Coronary Heart Disease mortality and morbidity. Therapy should be targeted at people who are at high risk of coronary heart disease rather than be based upon cholesterol levels. In asymptomatic people, at low risk of coronary heart disease, the costs of cholesterol lowering using statins are high relative to the benefits and their use is contentious. Cholesterol lowering is one of a number of methods of reducing the risk of cardiovascular disease. Cholesterol plays a central role in many biochemical processes, but is best known for the association of cardiovascular disease with various lipoprotein cholesterol transport patterns and high levels of cholesterol in the blood. The cost-effectiveness of some anti-hypertensives, aspirin and beta-blockers is greater than statins.Greater priority should be given to the appropriate use of other drug treatments and nonpharmacological interventions in the primary and secondary prevention of coronary heart disease. The average level of blood cholesterol within a population an important determinant of the Coronary Heart Disease risk of the population. In countries where the average cholesterol levels of the population are low, Coronary Heart Disease tends to be uncommon. Prospective studies show that groups of individuals with lower levels of cholesterol run less risk of developing Coronary Heart Disease. The association between cholesterol level and future risk Coronary Heart Disease is graded and continuous: there is no threshold above which Coronary Heart Disease risk begins to increase. There has been some concern that low levels of blood cholesterol and triglycerides increase the risk of mortality from causes other than Coronary heart disease, including cancer, respiratory disease, liver disease and accidental/violent death. High blood triglycerides as a Coronary Heart Disease risk factor is a subject that has received some debate. Associated with mild to moderate elevations in plasma triglycerides is the dense (small) LDL subclass pattern, (LDL pattern B), which is a heritable trait determined by a single major dominant gene (the alp locus). Approximately 30-35% of people are heterozygous (one gene pair affected) for alp and another 5% are homozygous (two gene pair affected). 50% of men with heart disease express this trait. This dense LDL subspecies is a marker for a common genetic trait that effects lipoprotein metabolism and increases Coronary Heart disease risk. A gene responsible has been located on chromosome 19, near the genes for the LDL receptor and insulin receptor. Other locations on the human genome have been identified that impact expression of this trait. The LDL pattern B trait is associated with a tendency toward elevated levels of triglyceride, and reduced levels of HDL, however, the LDL pattern B can persist, even when levels of triglyceride and HDL are normal. Many years of scientific investigation at the Lawrence Berkeley Laboratory, and other centers, has elucidated the reasons why the small LDL trait increases heart disease risk so significantly. Lipoproteins can become oxidized which enhances their ability to contribute to atherosclerosis and small LDLs are more susceptible to oxidation than large LDLs. Because of their small size, they weasel their way into the arterial wall more rapidly than larger LDLs. The ability of the blood vessel to respond normally to contraction and relaxation is impaired by the small LDL, and, it also interferes with some aspects of normal blood coagulation. Individuals with small LDLs also tend to have higher blood insulin levels and higher blood pressure. The reverse cholesterol transport system appears to be impaired and is reflected by low HDL and in particular, low HDL. In coronary heart disease regression trials, patients with a predominace of small LDL, and/or a reduction in small LDL have been linked to improvement in blocked arteries. Cholesterol lowering medications and low fat diet, have different effects based on the LDL subclass pattern. Thus, it is important to determine an individuals pattern in order to select the correct treatment. Heart disease is caused by narrowing of the coronary arteries that feed the heart. Like any muscle, the heart needs a constant supply of oxygen and nutrients, which are carried to it by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by cholesterol and fat deposits--a process called atherosclerosis--and cannot supply enough blood to the heart, the result is coronary heart disease (CHD). If not enough oxygen-carrying blood reaches the heart, you may experience chest pain called angina. If the blood supply to a portion of the heart is completely cut off by total blockage of a coronary artery, the result is a heart attack. This is usually due to a sudden closure from a blood clot forming on top of a previous narrowing. Coronary Heart disease which caused by high blood cholesterol may represent as Angina Pectoris. A person who suffers from angina pectoris has coronary arteries that are wide enough to supply blood to the heart during normal activities, but too narrow to deliver sufficient blood and oxygen when extra work is required of the heart. An attack of angina develops when the heart must work harder than normal and the muscle cells that make up the heart do not receive enough oxygen. Angina is typically felt as a heavy, squeezing pain in the center of the chest. The pain may also spread to the neck, jaw, back, and left arm. An attack of angina may last for several minutes and is often brought on by physical activity, emotional stress, cold weather, or digestion of a heavy meal—all factors that can increase the heart’s workload. There are three types of angina : Stable angina, Unstable angina, and Variant angina (coronary spasm) Stable angina: A type of angina brought on by an imbalance between the heart’s need for oxygen-rich blood and the amount available. It is "stable," which means the same activities bring it on; it feels the same way each time; and is relieved by rest and/or oral medications. Stable angina is a warning sign of heart disease and should be evaluated by a doctor. If the pattern of angina changes, it may progress to unstable angina. Unstable angina: This type of angina is considered an acute coronary syndrome. It may be a new symptom or a change from stable angina. The angina may occur more frequently, occur more easily at rest, feel more severe, or last longer. Although this angina can often be relieved with oral medications, it is unstable and may progress to a heart attack. Usually more intense medical treatment or a procedure is required. Unstable angina is an acute coronary syndrome and should be treated as an emergency. Variant angina: A coronary artery can go into spasm, disrupting blood flow to the heart muscle (ischemia). It can occur in people without significant coronary artery disease. However, two thirds of people with variant angina have severe disease in at least one vessel, and the spasm occurs at the site of blockage. This type of angina is not common and almost always occurs when a person is at rest - during sleep. You are at increased risk for coronary spasm if you have: underlying coronary artery disease, smoke, or use stimulants or illicit drugs (such as cocaine). If a coronary artery spasm is severe and occurs for a long period of time, a heart attack can occur. Other major independent risk factors (smoking, high blood pressure, diabetes, physical inactivity, and obesity) also exist and should be considered in defining individual risk of coronary heart disease. Smokers with high blood pressure have three times the risk of dying of coronary heart disease compared to non-smokers with low blood pressure where both have the same level of blood cholesterol. Risk scoring systems developed from the Heart study were no more accurate in predicting who suffered from coronary heart disease with blood cholesterol included than without, highlighting the importance of these other major risk factors. If you have more than two of the risk factors listed, you should discuss your risk factors with your doctor. Your goal is to decrease your risk factors and lessen your risk for future heart disease events. This is true if you do not have heart or blood vessel disease, if you are being treated medically for heart or blood vessel disease, or you have undergone a procedure (angioplasty, stents, bypass surgery) for heart or blood vessel disease. The example of the other disease which related to Coronary Heart disease caused by high blood cholesterol is Heart Failure. Heart failure means the heart is unable to pump blood as well as it should. Heart failure does not mean the heart has stopped working. Coronary artery disease causes decreased blood flow to the heart muscle. If the arteries become blocked, the heart becomes starved for oxygen and nutrients (ischemia). In a short time, damage to the heart muscle (a heart attack) occurs. The damaged area can not pump normally, causing heart failure. Other causes include: Cardiomyopathy: damage to the heart muscle from infection, alcohol or drug abuse, pregnancy or no apparent cause Conditions that overwork the heart: high blood pressure (hypertension), valve disease, thyroid disease, kidney disease, diabetes mellitus or heart defect 4.2 The correlations with the Subject A population approach focuses more on trying to reduce levels of risk factors in the population as a whole. The logic here is that even though coronary heart disease risk for any individual may be lowered by only a small amount, the population effect could be substantial because so many people are affected. Furthermore, a large percentage of events occur in people who are at only average risk and who would otherwise be missed by approaches targeted at those at high risk. Public health policy is based on a combination of population and targeted approaches. Although blood cholesterol is an important risk factor, by itself it is a relatively poor predictor of who will go on to have a coronary heart disease event. The relationship between blood cholesterol and coronary heart disease rates in men, only 42% of those who will suffer an event over 15-years have blood cholesterol over 6,5 mmol/l. The other research shows that the distribution of blood cholesterol in men aged 40-60 who subsequently went on to suffer from coronary heart disease and those who did not, overlap considerably. The prevalence of raised cholesterol increases with age in both men and women. In men the proportion with cholesterol levels of 5.0mmol/l and above increases from 26% in those aged 16-24 to around 80% in those aged 45-64, with a slight decrease in the two oldest age groups. In women cholesterol levels of 5.0mmol/l or above increase from 31% in those aged 16-24 to 84% in those aged 55-64, with, like men, a slight decrease in those over 65 years. Men with the lowest cholesterol levels have higher rates of total mortality than men with higher (but still well below average) levels. Several studies have now demonstrated that this phenomenon is mostly, entirely, due to the fact that this group of people with low cholesterol levels includes a disproportionate number whose cholesterol has been reduced by illness – early cancer, respiratory disease, gastrointestinal disease and alcoholism, among others. Thus it is the pre-existing disease which causes both the low cholesterol and raised mortality and not the low cholesterol levels themselves which produce the elevated mortality rates. So, men in their 40s have a higher risk of CHD than women. But, as women get older, their risk increases so that it is almost equal to a man's risk. 4.3 The correlations with the Geography and Year Differences in average levels of blood cholesterol between communities or populations are largerly determined by differences in diet. Cities with high dietary saturated fat intake and a low ratio of polyunsaturated to saturated fatty acids like in West Jakarta, have high average cholesterol levels. Randomised controlled trials in Jakarta Institutional settings demonstrate that if components of the diets of individuals are changed substantially then large changes in blood cholesterol levels can be achieved. Mean total blood cholesterol levels in both men and women in West Jakarta fell between 1994 and 1998, but remained stable between 2001 and 2006. The prevalence of raised total cholesterol fell between 1997 and 2001, but increased slightly between 2001 and 2006. This increase was not consistent across all age groups but was concentrated in the younger age groups. In older age groups (55 and older in men and 65 and older in women) the prevalence of raised total cholesterol has fallen steadily over the past decade.

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