Emerging Risk Factors
The metabolic syndrome comprises a clustering of cardiovascular risk factors
including abdominal obesity, insulin resistance, elevated triglycerides,
low HDL-C and hypertension. The presence of metabolic syndrome increases
cardiovascular risk by 1.6-2.6 fold. The greater risk occurs in patients
with type 2 diabetes mellitus or elevated hs-CRP. Criteria for metabolic
syndrome include ≥ 3 of the following parameters:
- Abdominal obesity (waist circumference in males >102 cm or 40 inches
or in females >88 cm or 34.6 inches).
- Triglycerides ≥ 1.7 mmol/L
- HDL <1 mmol/L in males or < 1. 3 mmol/L in females
- BP ≥ 130/85
- FBG 6.2-7 mmol/L
The prevalence of metabolic syndrome in North America is approximately
25% and this reflects the rising prevalence of obesity and inactivity.
Metabolic syndrome is associated with production of a variety inflammatory
proteins including CRP. The presence of metabolic syndrome is a strong
predictor of new onset of diabetes. In addition metabolic syndrome is
associated with the presence of more atherogenic small dense LDL particles
and elevated apoliprotein B levels which reflects the total number of
atherogenic lipid particles.
The battle against metabolic syndrome is intricately linked to the battle
against obesity and diabetes and includes:
- Weight reduction ≥ 5% body weight.
- Regular physical activity≥ 30 minutes 5 times/week
- Targeted therapy of dyslipidemia to lower LDL, raise HDL, lower triglycerides
and optimize TC/HDL (<4/1) and LDL/HDL (<3/1) ratios
- Tight BP control optimally including use of an ACE inhibitor
- Tight BS control to achieve euglycemia ASAP with oral hypoglycemic
therapy and insulin sensitizers as per CDA
Lipoprotein (a) is a newly recognized risk factor for heart disease. Lipoprotein
(a) is a type of LDL which is particularly atherogenic (causes cholesterol
deposits in arteries) and also appear to increase the risk of blood clot
formation in already narrowed arteries leading to heart attacks or strokes.
Lipoprotein (a) is dependent on genetic factors and hence levels are often
found to be elevated in families with a history of early heart disease.
A normal lipoprotein (a) level is about 15 mg/dl. Heart disease risk increases
with levels above 30 mg/dl. The only effective medication for ipoprotein
(a) is Niacin, but the risk associated with lipoprotein (a) decreases
if LDL cholesterol is lowered by diet or other medications. Lipoprotein
(a) is measured in specialized laboratories.
Apolipoprotein B is a protein which associates with atherogenic lipid
particles including VLDL, intermediate density lipoprotein, LDL and lipoprotein
(a). Apolipoprotein B has been shown to be a better estimate of cardiovascular
events than the LDL-C level and in conjunction with TG > 1.5 mmol/L,
an apolipoprotein B of > 1.2 g/L imparts the highest risk and is associated
with the presence of smaller denser more atherogenic LDL particles. Measurement
of apolipoprotein B is independent of TG levels and levels may be of value
in assessing adequacy of statin therapy. Optimal level of apolipoprotein
B in patients at high risk for cardiovascular events is < 0.9 g/L.
Homocysteine is an amino acid in the blood. Amino acids are the building
blocks of proteins. Build-up of homocysteine in the blood may be due to
vitamin deficiencies or hereditary deficiencies of enzymes that normally
break down homocysteine. An excess of homocysteine in the blood has been
linked to premature vascular disease (hardening of the arteries) and early
development of stroke, heart attack or peripheral vascular disease. There
is as yet, no proof that treating homocysteine excess with vitamins know
to work with certain enzymes to increase the breakdown of homocysteine,
has any effect on clinical outcome. Nevertheless, in patients with
premature atherosclerosis or in patients with no obvious risk factors
who develop CAD, it is reasonable to test for homocysteine and to treat
with appropriate doses of Vitamins B6, B 12 and folic acid (Folic acid
1-5 mg, B6 10-50 mg, B12 250-500 mcg). The target level for homocysteine
is < 10 µmol/L.
CRP (C-reactive protein)
Atherosclerosis is an inflammatory disease. Inflammatory cells are active
within the cholesterol plaque ingesting cholesterol to aide in its removal.
CRP or C-reactive protein is a marker of vascular inflammation. CRP has
been shown to be a strong predictor of future cardiovascular events. An
increased CRP at admission has been shown to be a marker for worse short
and long term prognosis in patients with unstable angina. In one recent
trial CRP was superior to an elevated LDL as a predictor of primary cardiovascular
events. CRP and LDL are independent, thus the use of both markers has
been shown to be superior to the use of either marker alone. Almost 50%
of cardiovascular events occur in patients with normal LDL levels. The
measurement of CRP in these patients helps to identify those patients
at greater risk. Low risk is defined as hs-CRP (high sensitivity-CRP)
<1 mg/ml; average risk as hs-CRP 1.0 - 3.0 mg/L and high risk as hs-CRP
3.0-10 mg/L. If hs-CRP is >10 mg/L, the test should be repeated and
patient examined for sources of infection or inflammation. Risk estimates
based on hs-CRP levels are not affected by the use of HRT (hormone replacement
Unfortunately high sensitivity CRP (hs-CRP) assays are not yet widely
available. When they are, CRP will become a useful test to predict cardiovascular
risk, particularly in those patients with low LDL levels and the absence
of other traditional cardiac risk factors.