The biochemical or physiological risk factors are those abnormalities, some of which are metabolic in nature, which give rise to atherosclerosis and Cardio-vascular diseases. They act as fore-111nner for the development of heart attack,stroke, renal failure and peripheral vascular disease. The diseases or conditions are - Hypertension, diabetes, dyslipidaemia, obesity rind clustering of then1 giving rise to metabolic syndrome.
Hypertension
The importance of elevated BP as a risk factor for CAD, heart failure, cerebro-vascular disease and renal failure in both Inen and woinen has been clarified in a large number of epidemiological studies. Hypertension causes structural and functional changes in the vessel wall - as well as in the heart itself. The vessels are narrowed increasing the resistance to flow; endothelial damage promotes atherosclerosis and both atheroma and vasospasm can easily cause complete blockage in those narrowed arteries. Increase in resistance to flow leads to enlargement of the lieart (left ventricular hy pertrophy), which raises oxygen demand. That in itself increases the risk of CAD. Systolic BP is at least as powerful a coronilly risk factor as the diastolic BP, and isolated systolic Hypertension is now established as a major hazard for coronaiy disease and stroke.
Risk is related to the level of blood pressure and increases as the blood pressure rises - there is no definite cut-off point. Hypertension not only p~.omotes atheroma but also increases the oxygen demand of the heart and thereby aggravates ischaemia. Clinical trials of BP lowering using different di-ugs have clearly shown that the risks associated with increased BP call be substintially reduced, especially for stroke, but also for CAD and heart failure: a goal BP of < 130185 mmHg is appropriate for primary and secondary prevention. The BP goal need to be even lower in diabetic patients as well as in patients with renal parenchymal disease in whoin renal protection may occur at values even less than 80mnlHg.
Dyslipidaemia
The results of epidemiological studies, as well as trials with angiographic or clinical endpoints, confirin the importance of various lipid fractiolls in the pathogenesis of atherosclerosis. There is a strong and graded positive association between total and LDL cholesterol and risk of vascular events (mainly ischaelnic heart disease) extending over a wide range of cholesterol concentrations. This association applies to individuals with or without established CAD as well as towomen and men. Other risk factors can substantially aggravate the effects of LDL cholesterol.
The other fraction of the lipid is HDL cholesterol. It is also called 'good' cholesterol as there is a strong and inverse associatioil between HDL cholesterol and the risk of CAD in both men and women and in subjects with or without established CAD; the lower the concentration of HDL-cholesterol the greater the rislc of CAD. The inverse association between HDL-cholesterol levels and CAD rislc at least equals the positive association between CAD iisk and serum LDL-cholesterol 1evels.There is now evidence from the Veterans Administration High-density Lipoprotein Cholesterol Intervention Study (VA-HIT) that the increase in HDL-cholesterol in CAD patients is followed by a significant decrease in major coronary events.
Triglycerides are the other lipid components in the blood 2nd they also contribute to an increased risk of coronary artery disease by a number of mechanisms. The triglyceiide rich lipoproteins rnay be independently atherogenic or they may promote atherosclcrosis by inducing a procoagulant state and promoting thrombosis.While level of individual lipid factor inay be important in the pathogenesis of coronary atherc%clerosis, interplay of different lipid fractions is much more significant. For example, at a given level of LDL cholesterol, the atherogenic potential is enhanced in presence of low HDL cholesterol level. Again, the ratio of total cholesterol (TC) to HDL cholesterol (HDLc) emerges as the lllost powei-ful predictor of atherosclerosis; a TC/HDLc ratio more than 4,5 is associated with high risk of CAD.
Glucose Intolerance and Diabetes
Insulin resistance, hy peiinsulinaenlia and glucose intolernnce appear to promote atherosclerosis. The prevalence of CAD rises from 2 per cent to 4 per cent in the general population to as high as 55 per cent anlong adult diabetic patients.Diabetes mellitus is an independent risk factor for CVD in both men and women.Excess risk for CVD can be found in patients with type one and type two DM, in patients in the prediabetic stages, and in patients with obesity and with the metabolic syndrome.
In diabetic patients the overall mortality from heart disease is lwice as great in men and is 4 to 5 tiines higher in women. Cardio-vascular disease represents over one-half of all deaths in both type one and type two DM. In addition, non-CV rnoaality is greater in diabetic compared with non-diabetic subjects, and this excess risk remains constant during long-term follow-up. Diabetes nlellitus has beenn considered as a CAD risk factor equivalent, In a prospective cohort study, the age-adjusted relative risk of death from any cause was 2.3 among men with DM but without CAD, 2.2 among men with CAD and without DM, and 4.7 among men with both DM and CAD. Patients with DM are more likely to die after an MI than patients without DM.Diabetes is also associated with an increased risk 01 morbidity in patients with CAD. Diabetes mellitus and obesity are predictors of MI. About one-quarter of patients who present with an acute MI have DM. Diabetes mellitus is a predictor of ischemic stroke and heart failure, and diabetes increases the overall CV risk in patients with heart failure. Diabetic patients undergo invasive management less often, and when referred for coronary angiography, they wait longer. In addition,quality of life is reduced in DM patients compved with nondiabetic patients.
Hypertension
The importance of elevated BP as a risk factor for CAD, heart failure, cerebro-vascular disease and renal failure in both Inen and woinen has been clarified in a large number of epidemiological studies. Hypertension causes structural and functional changes in the vessel wall - as well as in the heart itself. The vessels are narrowed increasing the resistance to flow; endothelial damage promotes atherosclerosis and both atheroma and vasospasm can easily cause complete blockage in those narrowed arteries. Increase in resistance to flow leads to enlargement of the lieart (left ventricular hy pertrophy), which raises oxygen demand. That in itself increases the risk of CAD. Systolic BP is at least as powerful a coronilly risk factor as the diastolic BP, and isolated systolic Hypertension is now established as a major hazard for coronaiy disease and stroke.
Risk is related to the level of blood pressure and increases as the blood pressure rises - there is no definite cut-off point. Hypertension not only p~.omotes atheroma but also increases the oxygen demand of the heart and thereby aggravates ischaemia. Clinical trials of BP lowering using different di-ugs have clearly shown that the risks associated with increased BP call be substintially reduced, especially for stroke, but also for CAD and heart failure: a goal BP of < 130185 mmHg is appropriate for primary and secondary prevention. The BP goal need to be even lower in diabetic patients as well as in patients with renal parenchymal disease in whoin renal protection may occur at values even less than 80mnlHg.
Dyslipidaemia
The results of epidemiological studies, as well as trials with angiographic or clinical endpoints, confirin the importance of various lipid fractiolls in the pathogenesis of atherosclerosis. There is a strong and graded positive association between total and LDL cholesterol and risk of vascular events (mainly ischaelnic heart disease) extending over a wide range of cholesterol concentrations. This association applies to individuals with or without established CAD as well as towomen and men. Other risk factors can substantially aggravate the effects of LDL cholesterol.
The other fraction of the lipid is HDL cholesterol. It is also called 'good' cholesterol as there is a strong and inverse associatioil between HDL cholesterol and the risk of CAD in both men and women and in subjects with or without established CAD; the lower the concentration of HDL-cholesterol the greater the rislc of CAD. The inverse association between HDL-cholesterol levels and CAD rislc at least equals the positive association between CAD iisk and serum LDL-cholesterol 1evels.There is now evidence from the Veterans Administration High-density Lipoprotein Cholesterol Intervention Study (VA-HIT) that the increase in HDL-cholesterol in CAD patients is followed by a significant decrease in major coronary events.
Triglycerides are the other lipid components in the blood 2nd they also contribute to an increased risk of coronary artery disease by a number of mechanisms. The triglyceiide rich lipoproteins rnay be independently atherogenic or they may promote atherosclcrosis by inducing a procoagulant state and promoting thrombosis.While level of individual lipid factor inay be important in the pathogenesis of coronary atherc%clerosis, interplay of different lipid fractions is much more significant. For example, at a given level of LDL cholesterol, the atherogenic potential is enhanced in presence of low HDL cholesterol level. Again, the ratio of total cholesterol (TC) to HDL cholesterol (HDLc) emerges as the lllost powei-ful predictor of atherosclerosis; a TC/HDLc ratio more than 4,5 is associated with high risk of CAD.
Glucose Intolerance and Diabetes
Insulin resistance, hy peiinsulinaenlia and glucose intolernnce appear to promote atherosclerosis. The prevalence of CAD rises from 2 per cent to 4 per cent in the general population to as high as 55 per cent anlong adult diabetic patients.Diabetes mellitus is an independent risk factor for CVD in both men and women.Excess risk for CVD can be found in patients with type one and type two DM, in patients in the prediabetic stages, and in patients with obesity and with the metabolic syndrome.
In diabetic patients the overall mortality from heart disease is lwice as great in men and is 4 to 5 tiines higher in women. Cardio-vascular disease represents over one-half of all deaths in both type one and type two DM. In addition, non-CV rnoaality is greater in diabetic compared with non-diabetic subjects, and this excess risk remains constant during long-term follow-up. Diabetes nlellitus has beenn considered as a CAD risk factor equivalent, In a prospective cohort study, the age-adjusted relative risk of death from any cause was 2.3 among men with DM but without CAD, 2.2 among men with CAD and without DM, and 4.7 among men with both DM and CAD. Patients with DM are more likely to die after an MI than patients without DM.Diabetes is also associated with an increased risk 01 morbidity in patients with CAD. Diabetes mellitus and obesity are predictors of MI. About one-quarter of patients who present with an acute MI have DM. Diabetes mellitus is a predictor of ischemic stroke and heart failure, and diabetes increases the overall CV risk in patients with heart failure. Diabetic patients undergo invasive management less often, and when referred for coronary angiography, they wait longer. In addition,quality of life is reduced in DM patients compved with nondiabetic patients.
Obesity
Obesity results from a cornplix interaction of genetic predisposition and environmeiltal factors operating throughout an individual's lifetime. It is an inlportant iisk factor for CAD and prospective epidemiological studies have shown that excess body weight is directly related to an enhanced Cardio-vascular mortality.Overweight individuals have a two-fold increase in the risk of developiilg CAD and this increased risk is related to lipid disturbances, Hypertension, and insulin resistance with glucose intolerance along with a pro-inflammatory and prothrombotic effect. Furthermore, obesity is independently associated with left ventricular hypertrophy, which in itself is a risk factor for CAD.
Obesity is commonly defined as 20 per centage increase in body weight over the ideal body weight. However a lllore precise method is to calculate the Body Mass Index (BMI) - which is the ratio of the weight in (Kg) to the height in (Metre)2.The different grades of obesity based on BMI are as follows:In considering obesity as a risk factor, one should understand that it is not only the degree of obesity but also the distl-ibution of fat that plays impostant role. Obesity has been defined as central (abdominal) and peripheral (hip) type depending on the place where excess fat accumulates. The former is also called 'apple' type and the latter is called 'pear' type obesity. Central or abdominal obesity with an increased intra-abdominal fat mass is more strongly associated with vascular disease than general adiposity or peripheral adiposity. The abdominal fat inass is not an inert tissue but a inetabolically active organ that produces a number of hLumful substances called adipokines and is linked to insulin resistance. Visceral adipose Itissue generates greater quantities of angiotensinogen, plasrninogen activator inhibitor-1 (PAI-I), tumour.necrosis factor - alpha (TNF-alpha), and resistin, and less of leptin and adinopectin. The abdominal distribution of'fat has been associated with Hypertension, hypercholesterolaemia, low HDL cholesterol,hypert"glyceridaernia and elevated levels of fibrinogen - and each of these abnormalities are known risk factors for CAD.
Obesity results from a cornplix interaction of genetic predisposition and environmeiltal factors operating throughout an individual's lifetime. It is an inlportant iisk factor for CAD and prospective epidemiological studies have shown that excess body weight is directly related to an enhanced Cardio-vascular mortality.Overweight individuals have a two-fold increase in the risk of developiilg CAD and this increased risk is related to lipid disturbances, Hypertension, and insulin resistance with glucose intolerance along with a pro-inflammatory and prothrombotic effect. Furthermore, obesity is independently associated with left ventricular hypertrophy, which in itself is a risk factor for CAD.
Obesity is commonly defined as 20 per centage increase in body weight over the ideal body weight. However a lllore precise method is to calculate the Body Mass Index (BMI) - which is the ratio of the weight in (Kg) to the height in (Metre)2.The different grades of obesity based on BMI are as follows:In considering obesity as a risk factor, one should understand that it is not only the degree of obesity but also the distl-ibution of fat that plays impostant role. Obesity has been defined as central (abdominal) and peripheral (hip) type depending on the place where excess fat accumulates. The former is also called 'apple' type and the latter is called 'pear' type obesity. Central or abdominal obesity with an increased intra-abdominal fat mass is more strongly associated with vascular disease than general adiposity or peripheral adiposity. The abdominal fat inass is not an inert tissue but a inetabolically active organ that produces a number of hLumful substances called adipokines and is linked to insulin resistance. Visceral adipose Itissue generates greater quantities of angiotensinogen, plasrninogen activator inhibitor-1 (PAI-I), tumour.necrosis factor - alpha (TNF-alpha), and resistin, and less of leptin and adinopectin. The abdominal distribution of'fat has been associated with Hypertension, hypercholesterolaemia, low HDL cholesterol,hypert"glyceridaernia and elevated levels of fibrinogen - and each of these abnormalities are known risk factors for CAD.
The distributiontof fat and type'of obesity can be assessed by simple clinical methods like ~neasuring the waist circumference or waist-hip ratio (WHR) in an individual. Men should have a WHR equal to or less than 0.95, whereas in women it should not be more than 0.80. The waist circumference should not be more than 90 cm in women and 100 cm in men.While measurement of weight gives a general idea about the presence of obesity,the BMI, WHR and whst circumference are more reliable estimates of the degree of obesity and its pathologic effects. The recent INTERHEART study has shown that the WHR is the strongest anthropoinellic measure associated with risk of myocardial infarction, and is superior to BMI.
Metabolic Syi~drome
As discussed, the risk factors like obesity, high blood pressure, high blood glucose or impaired glucose tolerance, and dyslipidaeinia are very iinportant from the pathogenetic point of view. While each of these factors can be present singly and cad cause or predispose to Cardio-vascular diseases individually, more often than not they are clustered together in the same person, multiplying the risk several fold. The term 'Metabolic syndrome ' is applied to the clustering of these risk factors and the rising incidence of this syndrome is considered to be the main cause of increasing number of Cardio-vascular diseases and diabetes, especially in the Indian subcontinent, Though the clustering of the risk factors was not unknown earlier, it was only in 1988 that the concept of a syndrome with these clustered abnormalities was put forward by Prof Gerald Reavan in his famous Banting lecture and he coined the term syndrome X to describe that grouping, As insulin resistance was thought to be the priinary mechanism underlying these abnormalities, the name insulin resistance syndl.omc wns also applied. Subsequently metabolic syndrome became the term of choice when WHO in 1999 and The Third Report of the National Cholesterol Education Program's Adult Treatinen1 Panel (NCEP ATP-111) independently developed the criteria using that name.
Metabolic syndrome significantly increases the risk of Cardio-vascular diseases(CVD) and diabetes. In fact the interest in metabolic syndrome stemmed from the observation of a close correlation between the rising incidence of CVD and the salient features of this condition, particularly abdominal obesity and insulin resistance. The relative risk of CAD ranges from 1.5 to 3 depending on the stage of progression and the risk of diabetes increases five-fold compared to those without metabolic syndrome. The development of diabetes increases the Cardio-vascular risk still further. In the NHANES I11 study, the age adjusted prevalence of coronary artery disease was highest (19.2 per cent) in patients with both type two diabetes and metabolic syndrome, followed by metabolic syndrome without type two diabetes (13.9 per cent). Increased risks of CAD and/or all cause mortality have been demonstrated in Nurses' Health study and in AFCAPSIT~XCAPS also.
Another important point to note is that multiple risk factors present in metabolic syndrome have a multiplicative effect; risk rises geometrically instead of linearly,being more than the sum of risks ascribed to.individua1 risk factors.
Metabolic Syi~drome
As discussed, the risk factors like obesity, high blood pressure, high blood glucose or impaired glucose tolerance, and dyslipidaeinia are very iinportant from the pathogenetic point of view. While each of these factors can be present singly and cad cause or predispose to Cardio-vascular diseases individually, more often than not they are clustered together in the same person, multiplying the risk several fold. The term 'Metabolic syndrome ' is applied to the clustering of these risk factors and the rising incidence of this syndrome is considered to be the main cause of increasing number of Cardio-vascular diseases and diabetes, especially in the Indian subcontinent, Though the clustering of the risk factors was not unknown earlier, it was only in 1988 that the concept of a syndrome with these clustered abnormalities was put forward by Prof Gerald Reavan in his famous Banting lecture and he coined the term syndrome X to describe that grouping, As insulin resistance was thought to be the priinary mechanism underlying these abnormalities, the name insulin resistance syndl.omc wns also applied. Subsequently metabolic syndrome became the term of choice when WHO in 1999 and The Third Report of the National Cholesterol Education Program's Adult Treatinen1 Panel (NCEP ATP-111) independently developed the criteria using that name.
Metabolic syndrome significantly increases the risk of Cardio-vascular diseases(CVD) and diabetes. In fact the interest in metabolic syndrome stemmed from the observation of a close correlation between the rising incidence of CVD and the salient features of this condition, particularly abdominal obesity and insulin resistance. The relative risk of CAD ranges from 1.5 to 3 depending on the stage of progression and the risk of diabetes increases five-fold compared to those without metabolic syndrome. The development of diabetes increases the Cardio-vascular risk still further. In the NHANES I11 study, the age adjusted prevalence of coronary artery disease was highest (19.2 per cent) in patients with both type two diabetes and metabolic syndrome, followed by metabolic syndrome without type two diabetes (13.9 per cent). Increased risks of CAD and/or all cause mortality have been demonstrated in Nurses' Health study and in AFCAPSIT~XCAPS also.
Another important point to note is that multiple risk factors present in metabolic syndrome have a multiplicative effect; risk rises geometrically instead of linearly,being more than the sum of risks ascribed to.individua1 risk factors.
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