Predicting Cardiovascular Diseases in the Young

PREDICTING CARDIOVASCULAR DISEASE IN THE YOUNG

Coronary heart disease remains the leading cause of death and it is emerging more so in the young population. The South Asian countries, mainly India, Pakistan, Bangladesh, Sri Lanka and Nepal account for about a quarter of the world population and contribute the highest proportion of cardiovascular diseases compared with any other region globally. Deaths related to cardiovascular disease occur 5 to 10 years earlier in South Asian Countries than in Western countries according to a recent study (1).

The researchers found that the prevalence of protective risk factors (leisure time physical activity, regular alcohol intake, and daily intake of fruits and vegetables) were markedly lower in South Asian study participants compared with those from other countries. Also some harmful factors were more common in native South Asians than in individuals from other countries: history of diabetes, current and former smoking, history of hypertension, psychosocial factors such as depression and stress at work or home, and elevated ApoB/ApoA-I ratio (a protein/lipid). This suggests that lifestyle changes implemented early in life have the potential to substantially reduce the risk of AMI in South Asians.

RISK FACTORS

Major coronary disease risk factors, many of which are modifiable, are strong contributors to prediction of future risk, even in young men. These may help in formulating appropriate strategies to identify young men at heightened risk for death from coronary heart disease in later adulthood.

High cholesterol and high blood pressure are two of the leading risk factors for heart disease, heart attack and stroke. High LDL cholesterol can cause atherosclerosis causing narrowing and hardening of the arteries. Hypertension, can weaken the arterial walls and make them more prone to atherosclerosis. Both conditions can lead to thrombi that can block blood flow and result in a heart attack or stroke. Most cases of atherosclerotic vascular disease become clinically apparent in patients aged 40-70 years. Autopsy studies show that coronary atherosclerosis begins as early as 20 years of age and in a recent study found severely stenotic coronary arteries (narrowing more than 40%) in 19% of men in their early thirties.

1. SERUM CHOLESTEROL – A recent study demonstrated the ability of serum cholesterol level and other well-known risk factors for coronary heart disease (particularly age, systolic blood pressure, cigarette smoking, and educational level) to predict death from coronary heart disease over 20 years in men 18 to 39 years of age (2). Relative risks for most of the major risk factors were of similar magnitude in young men and middle-aged men, and the relative risk associated with an elevated serum cholesterol level was found to be significantly higher in young men than in middle-aged men. This adds to the evidence that early development of coronary atherosclerosis is associated with risk factors which are largely modifiable. Furthermore, it indicates that it would be worthwhile to assess young people (e.g. for cholesterol) who are genetically predisposed to heart disease so they can make early lifestyle changes if necessary.

The National Cholesterol Education Program (NCEP) recommends cholesterol screening in all adults 20 years of age or older.

2. LDL/ Oxidised LDL – The mechanisms of atherogenesis remain uncertain. The “response to injury“ theory is most widely accepted. Probable causes of endothelial injury include LDL cholesterol; infectious agents; toxins, including the by-products of cigarette smoking; hyperglycemia; and hyperhomocystinemia.

Elevated serum levels of LDL cholesterol overwhelm the antioxidant properties of the healthy endothelium and result in abnormal endothelium metabolism of this lipid moiety.

Oxidized LDL is capable of a wide range of toxic effects and cell/vessel wall dysfunctions that are characteristically and consistently associated with the development of atherosclerosis. Furthermore, oxidized LDL activates inflammatory processes at the level

of gene transcription by up-regulation of nuclear factor kappa-B, expression of adhesion molecules, and recruitment of monocytes / macrophages. Circulating monocytes infiltrate the intima of the vessel wall , and these tissue macrophages act as scavenger cells, taking up LDL cholesterol and forming the characteristic foam cells of early atherosclerosis.

3. Lipoprotein (a) – Numerous studies have linked elevated plasma levels of lipoprotein (a), an LDL like moiety that circulates in the blood attached to apolipoprotein (a), with the development of coronary artery disease. This complex shares structural domains with the fibrinolytic enzyme plasminogen and may render the molecule prothrombotic. The LDL like moiety is susceptible to oxidation and may be particularly atherogenic.

4. High triglycerides are associated with low (HDL) high density lipoprotein and are a probable risk factor for vascular disease. Recent studies have shown that plasma triglyceride level is a risk factor for cardiovascular disease independent of high-density lipoprotein cholesterol level.

5. hs-CRP:- A growing number of studies have examined inflammatory markers as predictors of recurrent CVD and death in different settings, including the short-term risk, long-term risk, and risk after revascularization procedures such as percutaneous coronary intervention (PCI), including the risk of restenosis. Although several markers have been studied, the strongest association with prognosis has been with fibrinogen and hs-CRP.

hs-CRP consistently predicts new coronary events in patients with unstable angina and acute myocardial infarction.

For patients with acute coronary syndromes, cutpoints for elevated hs-CRP different than those for prediction in asymptomatic patients may be useful. For example, a level of >10 mg/L in acute coronary syndromes may have better predictive qualities, whereas a level of >3 mg/L may be more useful in patients with stable coronary disease.

In acute coronary syndromes, hs-CRP predicts recurrent myocardial infarction independent of troponins, which suggests it is not merely a marker for the extent of myocardial damage. Elevated hs-CRP levels also seem to predict prognosis and recurrent events in patients with stroke and peripheral arterial disease. This suggests that hs-CRP may have a role in risk stratification of patients with established CVD.

Measurement of markers should be done twice (averaging results), optimally two weeks apart, fasting or nonfasting in metabolically stable patients. If hs-CRP level is >10 mg/L, test should be repeated and patient examined for sources of infection or inflammation.

Relative Risk Category and Average hs-CRP Level

• Low <1 mg/L
• Average 1.0 to 3.0 mg/L
• High >3.0 mg/ L

6. Fibrinogen – Fibrinogen may be elevated in association with risk factors for atherosclerosis, including smoking, age, and diet. However this is a strong independent predictor of future cardiovascular events in apparently healthy patients.

7. C-reactive protein – C-reactive protein levels add to the predictive value of lipid parameters in determining the first myocardial infarction in apparently healthy men and women without a history of coronary heart disease.

A recent study found CRP concentrations to be higher in healthy Indian Asians than in European whites and was accounted for by greater central obesity and insulin resistance in Indian Asians. The results of the study suggest that inflammation or other mechanisms underlying elevated CRP values may contribute to the increased CHD risk among Indian Asians (3)

8. Homocysteinemia – Homozygous hyperhomocysteinemia is associated with extensive atherosclerosis at an early age. Atherogenesis due to hyperhomocysteinemia likely is due to oxidative damage to the endothelium followed by platelet activation and thrombus formation.

9. Insulin – Many people with diabetes develop heart disease, but a new study says that determining who has high levels of insulin in the blood — a condition that precedes diabetes — may better predict who is at risk for having a heart attack. Measurement of blood glucose and hemoglobin A1c is appropriate in patients with diabetes mellitus (4).

Tests available at Dr. Lal Path Labs:-

• Lipid profile basic ( cholesterol, Triglyceride ,Direct HDL, LDL ,VLDL)
• Lipid profile complete (Cholesterol, Triglyceride, HDL,VLDL,LDL by Electrophoresis, Chol/HDL Ratio,Chylomicrons)
• Lipid Profile Comprehensive ( Apolipoprotein A1, B & RATIO, Lp (a), Cholesterol, Triglyceride, LDL/HDL ratio,Chol/HDL ratio, Chylomicrons, LDL Subfractions, Homocysteine, Uric Acid, Fibrinogen, Cardio CRP, Plasminogen Activator inhibitor-1 (PAI-1)
• Lipid Extended 1 (Apolipoprotein A1, B & ratio,LP(A), Cholesterol, Triglyceride, LDL/HDL ratio,Chol/HDL ratio, Chylomicrons electrophoretically)
• Lipid Extended 11 (Apolipoprotein A1, B & ratio, Cholesterol,Triglyceride, LDL/HDL ratio,Chol/HDL ratio,Chylomicrons Electrophretically)
• Lipid Profile with LDL Subfraction.
• Homocysteine
• Cardio CRP
• Insulin

References:

1. JAMA and Archives Journals (2007, January 18). South Asians Have Higher Levels Of Heart Attack Risk Factors At Younger Ages. 2. EL Navas-Nacher et al. Risk factors for coronary heart disease in men 18 to 39 years of age. Annals of Internal Medicine 2001 134: 433-439. 3. John C. Chambers et al. C-Reactive Protein, Insulin Resistance, Central Obesity, and Coronary Heart Disease Risk in Indian Asians From the United Kingdom Compared With European Whites ,Circulation. 2001;104:145-150 4. American Heart Association (1998, August 14). High Blood Levels Of Insulin Possible Independent Predictor Of Heart Attack Risk.