Novel Risk Factors for Atherosclerosis (CRP, Lipoprotein-a, Fibrinogen and Homocysteine)

CRP- C-reactive protein: High CRP reflects inflammation, and has been shown to correlate with the occurrence of myocardial infarction and peripheral arterial disease. 

Homocysteine levels: It is a well known fact that homozygous hyperhomocystinemia is associated with early atherosclerosis and stroke. However, approximately 5-7% of the general population have mild elevations of plasma homocysteine, and recent research have focussed on refuting or establishing if this population is at a higher risk for cardiovascular events. A number of treatments have been postulated for those with high homocysteine levels including folic acid and pantothenic acid. 

Fibrinogen: In recent studies high levels of fibrinogen have been found to be strongly related to cardiovascular events in apparently healthy individuals.

Lipoprotein-A: Lipoprotein A is an LDL like substance in the blood that remains bound to apolipoprotein A. It may promote atherosclerosis by its ability to be oxidized. Some studies have shown that Vitamin B3 (Niacin) can decrease its levels but the clinical significance is still unclear.

Syncope (Causes and Pathophysiology)

Syncope is defined as loss of consciousness due to decreased cerebral perfusion. Causes of syncope can be classified as Neuroregulatory, Arrhythmias and Hemodynamic.

 

A. Neuroregulatory causes of syncope.

A.k.a.vasovagal syncope this is caused by a sudden decrease in blood pressure. Prolonged standing is a common cause especially is the subject is dehydrated.

 

The low BP is sensed by carotid baroreceptors, that increase cardiac rate and contractility. On the other hand pressure receptors in the walls of the underfilled left ventricle may sense high-pressure and cause paradoxical bradycardia and lower contractility.

B. Arrhythmia as a cause of syncope.

Common arrhythmias causing syncope include supraventricular tachycardia (SVT), ventricular tachycardia (VT), ventricular fibrillation, and severe bradycardia (eg, heart block).

 

C. Hemodynamic syncope

 

The following Structure defects in the heart can cause syncope.

 

•Hypertrophic obstructive cardiomyopathy (HOCM) or aortic stenosis leading to left sided outflow obstruction

•Pulmonary hypertension may cause syncope when the right ventricle fails to pump against the high pulmonary pressure.
•Ischemic heart disease due to anomalous coronary artery origin, hypercholesterolemia, or acute inflammatory diseases such as Kawasaki disease and myocarditis.

•Pericardial tamponade can cause hypotension and syncope secondary to decreased pre-load (ventricles can not fill well).

prGCD - plant cell expressed recombinant Glucocerebrosidase enzyme (GCD) for use in Gaucher's disease

This is a newly approved (partially approved for use by the Food and Drug Administration-FDA) drug for the treatment of patients with Gaucher's Disease.

Gaucher's disease is the most common lysosomal storage diseases in humans. It is caused by a hereditary deficiency of the enzyme glucocerebrosidase (also known as acid β-glucosidase). The enzyme acts on glucocerebroside which accumulates in its absence. Fatty material collects in the liver, kidneys, lungs, spleen, brain and bone marrow. The disease is inherited in autosomal recessive manner. The locus is on chromosome 1.

Traditionally Gaucher's disease has been classified in the following 3 types.

Type I (or non-neuropathic type) is the most common form of the disease. It occurs in 1 in 50,000 births. It is much more frequent in children of Ashkenazi Jewish heritage. Symptoms include enlarged liver and spleen. Bone marrow replacement can cause anemia, thrombocytopenia and leukopenia. The brain is usually not affected. Rarely there is lung or kidney impairment. These patients may live well into adulthood.

Type II (or acute infantile neuropathic form) typically begins in infancy and occurs in approximately 1 in 100,000 births. The diagnostic symptom of this type is extensive and progressive brain damage. Affected children do not usually live longer than 2 years of age.

Type III (the chronic neuropathic type) has a variable onset. Incidence is 1 in 100,000 births. It is characterized by slowly progressive but milder neurologic symptoms. Other major symptoms include an spleen and/or liver enlargement, seizures, bone marrow disorders and respiratory problems.

Osteoblastic and Osteoclastic markers

Bone Specific Alkaline Phosphatase – marker of Osteoblastic Activity

Tartrate Resistant Acid Phosphatase, Hydroxyproline and Deoxypyridinoline – markers of Osteoclastic Activity.

Fixed Wide Splitting

Fixed Wide Splitting of the second heart sound is present in patients with Atrial Septal Defect.

Thyroid function in pregnancy

Due to increased TBG (thyroid binding globulin) total thyroid hormones may be higher in pregnancy but the free fraction is normal. TSH is normal.

Weight gain in Pregnancy

Average weight gain in pregnancy is 30 lbs. Two lb in the first trimester and about 14 each in second and third trimesters.

What Worsens With VValsalva ?

Mitral Valve Prolapse and Hypertrophic Obstructive Cardiomyopathy are the only two murmurs that 'W'orsen 'W'ith 'W'alsalva maneuver.