Atherosclerotic cardiovascular disease, in all its clinical manifestations, represents a leading cause of mortality and morbidity in the world. Epidemiological studies have identified several important risk factors for cardiovascular disease including high blood pressure, obesity, smoking, and hypercholesterolemia.
Initially, the focus was on the diagnosis and treatment of heart diseases such as heart attacks. The unprecedented development in preventive cardiology research over the last two decades, have encouraged the practice of preventive medicine. This shift occurred because it was learnt that coronary heart events predominantly occur by atheroma rupture or erosion, which is most common in the intermediate stenosis, rather than high grade stenosis. The Framingham heart study show some risk factors which account for only 50% of cardiovascular events including type 2 diabetes and left ventricular enlargement.
The Framingham heart study has yielded two important lessons;
- The presence of one risk factor increases the likelihood of other risk factors as well.
- The presence of any of the traditional risk factors multiplies the risk of any other factor.
The search for additional and more precise markers of cardiovascular risk continues. It appears that abnormalities in the levels of cholesterol, sugar, blood pressure, and blood insulin leads to dysfunction of endothelial cells.
Dysfunctional endothelial cells do two things;
- By virtue of their effects on the media of an artery - there is vasoconstriction and increase in blood pressure.
- By virtue of changes in arterial structure and function, there is lipid deposition, inflammatory cell infiltration - causing atherosclerotic disease.
These two processes take place at the same time and either process may progress more rapidly than the other. If blood pressure becomes alleviated first, the physician is able to identify the patient and begins anti-hypertensive treatment. Because high blood pressure potentiates the process of atherosclerosis, such treatment can slow the atherosclerotic process.
However, in some patients, atherosclerotic disease progresses to heart disease before the elevation of blood pressure.
High blood pressure and atherosclerosis of blood vessels are most important reversible diseases of the cardiovascular system. They are the major killers at present. Identification and treatment of these patients before the onset of hypertension and coronary artery disease, may provide a better opportunity for reversing the disease processes and protecting patients from developing symptomatic cardiovascular diseases.
Hypertension
Hypertension, Obesity and type 2 diabetes are closely linked. Hypertension increases with increasing body weight, recent weight gains is more important in the development of hypertension. Hypertension is twice as common in patients with type 2 diabetes than in those without the disease and accounts for up-to 85% of excess cardiovascular diseases risks such as coronary heart disease, stroke, retinopathy and nephropathy. When hypertension coexists with diabetes, risk of stroke or heart-attack is doubled and the risk for developing end stage renal disease increases to 5-6 times compared to hypertensive patients without diabetes.
Essential hypertension is not a disease on its own but is associated with a cluster of cardiovascular risk factors which includes insulin resistance; hyperlipidemia; abdominal obesity; psychosocial stress; physical inactivity; smoking; hyperinsulinaemia; microalbuminuria; Endothelial dysfunction.
Hypertension in people with diabetes is also associated with salt sensitivity, volume expansion, increased propensity towards orthostatic hypotension, albuminuria; hypertension and nephropathy - exacerbate each other.
Classification
Blood Lipids
Cholesterol < 200mg/dl
LDL-C < 100mg/dl
HDL-C > 39mg/dl
TG < 150mg/dl
Blood Pressure:
Optimal: 120/80 mmHg
Normal: 130/85 mmHg
High Normal: 130/85 to 139/89 mmHg
Stage 1 HTN: 140/90 to 159/99 mmHg
Stage 2 HTN: 160/100 to 179/109 mmHg
Stage 3 HTN: > 180/110 mmHg
Diabetes Mellitus:
Normal fasting plasma glucose < 110 mg/dl
Impaired fasting plasma glucose: 110 - 126 mg/dl
Impaired glucose Tolerance: 2 Hours after glucose intake; Plasma glucose 140 to 200 mg/dl
Diabetes mellitus: Fasting Plasma glucose > 126mg/dl
2 Hours after glucose intake Plasma glucose > 200mg/dl
Overweight and Obesity:
Normal body mass index (BMI): weight in kgs/height in meter2
Normal BMI: ranging from 18.5 to 24.9
Overweight: ranging from 25 to 29.9
Obese: BMI 30 and above
Obesity
Obesity appears to be the most common and predictive factor for most of the metabolic abnormalities accompanying hypertension as well. Obesity is the major factor in the development of hypertension. Body fat distribution plays a critical role as a risk factor for hypertension. It was found that the cardiovascular and metabolic sequences of obesity were most marked in patients with abdominal obesity.
Obese patients tend to have increased blood volume and increased cardiac output. Peripheral vascular resistance is elevated in obese hypertensives compared with obese normotensives.
Recent studies have shown that obesity or recent weight gain accounted for 75% of all new cases of hypertension. The origin of sympathetic hyperactivity in obesity is related, at least in part, to hyperinsulinemia, because insulin stimulates the sympathetic nervous system, but factors such as leptin may contribute importantly as well.
There is a worldwide rapid increase in the prevalence of type 2 diabetes, due to factors such as improved affluence, longevity, and obesity. To prevent the development of diabetes and its partners in crime i.e. obesity and hypertension, must be identified at an early stage of risk and should be treated with preventive measures such as lifestyle advice and pharmacological therapy.
There are reasons to be concerned that the substantial gains that have been made in reducing the incidence of coronary disease mortality and morbidity will be lost as a result of this global epidemic. The approaches in treating the problem will inevitably require greater understanding of the implication of lifestyle and its alteration.
We are increasingly becoming aware that type 2 diabetes occurs only after years of metabolic alterations that are measurable but not symptomatic. Information on this metabolic substrate for diabetes can he gained by giving a glucose load to people without outright diabetes - impaired glucose tolerance.
The diagnostic criteria define diabetes as fasting plasma glucose of 126 mg/dl or greater, or plasma glucose levels of 200mg/dl or greater 2 hours after oral intake of 75g glucose. Impaired glucose tolerance (IGT) is defined as 2-h plasma glucose levels between 140 and 200 mg/dl, and impaired fasting glucose is defined as fasting plasma glucose levels of 110 - 126mg/dl. It is possible to identify patients who fit into these categories, and this categorization provides insight into the potential to prevent the overt future complications of diabetes.
Indeed, IGT is strongly predictive of future type 2 diabetes; approximately two-fifths of diagnosed individuals develop diabetes over 5 - 10 years. Accordingly, it is sensible for measures directed at preventing the development of type 2 diabetes to focus on people with IGT. People with insulin resistance are often hypertensive, and particularly in follow-up those with normal blood pressure at baseline are more likely to develop hypertension.
Diabetes has long been known to be a strong predictor of atherosclerosis, which is the main cause of morbidity and mortality in these patients. However, we have become aware in recent years that the increase to cardiovascular risk is present with the state of IGT, long before the manifestation of type 2 diabetes. Although it does not represent fully blown diabetes, IGT is associated with increased risk for macro vascular disease. In particular, the combination of IGT with known cardiovascular risk factors such as hypertension, dyslipidaemia, visceral obesity or hypercoagulability greatly increases the prognostic implications of the condition.
Hypertension is an important component in the cardiovascular risk factor syndrome and it is more prevalent in type 2 diabetes patients than in the general population. The benefits of controlling hypertension in diabetes have been shown in a number of landmark trials. There is a clear correlation between the degree of blood pressure reduction and cardiovascular risk reduction. It has been shown in recent trials that tight blood pressure control (target 135/82 mmHg) reduced the risk for diabetes - related end-points by 24% as compared with less control (target 154/87 mmHg). Tight blood pressure control also reduced strokes by 44% and microvascular end-points by 37%.
As hypertension is a risk factor for the development of type 2 diabetes, and IGT appears to be more common in hypertensive patients than in normotensive people. Intriguingly, recent clinical trials have suggested specific benefits of treatments that interfere with the rennin angiotensin system lead to delaying the onset of diabetes. The Losartan Intervention for Endpoint Reduction study showed that blood pressure control with the angiotensin receptor blocker losartan reduced the risk for developing type 2 diabetes by 25% as compared with the beta-blocker atenolol in hypertensive patients with left ventricular hypertrophy. The study on cognition and prognosis in elderly hypertensives indicated similar benefits (20% reduction in risk) with the ARB candesartan as compared with other therapies (mainly hydrochlorothiazide). Reports from the Heart Outcomes Prevention Evaluation study with the anigiotensin--converting enzyme inhibitor ramipril claim that the relative risk for developing diabetes is 0.66 versus placebo. There are also reports that ARBs such as losartan and valsartan improve insulin resistance in hypertensive patients.
Following the evidence provided by these trials, people previously considered normotensive, as well as hypertensive could have benefited more from treatment with ACE inhibitors or ARBs. In particular, we know far too little about the risk group with IGT. It is important to know whether ARB treatment in individuals with IGT will not only prevent the development of type 2 diabetes but also reduce the incidence of adverse cardiovascular outcomes. There is also an argument for combining RAS-inhibiting treatment with therapy aimed at decreasing post-prandial hyperglycaemia in order to reduce cardiovascular risk and prevent development of diabetes in individuals with IGT, importantly, because prevention is a case of treating groups that are at risk over many years, we would need to know the long-term effects of such antihypertensive drugs. This intriguing point has been taken up by many studies to indicate that if one risk factor expression properly controlled, is it possible to inhibit expression of other risk factors clinically.
Despite the importance of IGT, we are just beginning to get a reasonable view of the clinical epidemiological picture. Patients with IGT are asymptomatic (from the diabetes perspective), and are thus unlikely to seek the advice of physicians. Because the general awareness of IGT as a risk factor is low and screening has not been proven to be of benefit, physicians are not undertaking routine tests. The current estimate is that at least 200 million people worldwide have IGT, and there is a great need for preventative measures. In addition to insulin resistance and hypertension, the other factors of the metabolic syndrome are obesity (particularly large waist circumference), low high-density lipoprotein cholesterol and high triglycerides, needs to be properly managed. Each of these has an independent health risk, but when they occur in a cluster the risk for coronary arterial is magnified.
LDL - Cholesterol
High Risk Borderline High Risk Desirable
> 159mg/dl > 130mg/dl < 100mg/dl
Coronary Heart Disease
Stable angina: Pain on exertion No changes on ECG Normal cardiac enzymes
Unstable angina: Pain at rest: < 15min ECG changes present Normal cardiac enzymes
AMI: Pain at rest> 30 min ECG changes present raised cardiac enzymes