*High risk individuals include patients with diabetes, family history of cardiovascular disease (First degree relative age 50 in males, or age 60 in females), family history of familial dyslipidemia, or multiple CHD risk factors (i.e. smoking, HTN)
**Men at high risk, such as African Americans and men who have a first-degree relative (father, brother, or son) diagnosed with prostate cancer at an early age (younger than age 65), should begin testing at age 45.

Non-modifiable risk factors:

• Age:  >45 for men and >55 for women
• Male gender
• Family history:  MI or sudden death prior to age 65 in a female, or age 55 in a male first degree relative

Modifiable risk factors:

• Tobacco use
• Hypertension (>140/90 or the use of anti-hypertensive medications)
• Diabetes mellitus
• High LDL cholesterol
• Low HDL cholesterol (<35 mg/dL)
• Obesity
• Physical inactivity

Mr. Martin’s initial history confirms several risk factors of coronary heart disease. 

1. He is a male over the age of 45. 
2. He has a family history of premature coronary heart disease in two first-degree relatives (his father died of sudden death prior to the age of 55 and his brother suffered a myocardial infarction prior to the age of 55.)
3. Other risks factors include tobacco use, obesity and physical inactivity.

Of greatest concern is this patient’s hypertension, an additional risk factor for coronary heart disease.  He is also overweight, with a BMI (Body Mass Index) of 29. Overweight is defined as BMI greater than 25.5 and obesity is defined as BMI greater than 30, both are associated with increased risk for heart disease.

BMI Graph

To calculate your exact BMI number, multiple your weight in pounds by 705, divide by your height in inches, then divide again by your height in inches.

(Adapted from Obesity Education Initiative:  Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults, National Institutes of Health, National Heart, Lung, and Blood Institute, Preprint June 1998)

Patients with familial dysbetalipoproteinemia, Fredrickson phenotype III, may have tuberous xanthomata and xanthomata of the palmar creases. Patients with familial multiple lipoprotein hyperlipidemia, Fredrickson phenotype V, demonstrate eruptive xanthomata, lipemia retinalis and hepatosplenomegaly.

Both a fasting blood glucose determination and a lipid profile are important pieces of laboratory data to help further assess this patient’s risk for coronary heart disease.

The LDL cholesterol may be calculated using the Freidewald formula:

  LDL = Total cholesterol - HDL - Triglycerides/5

Using this equation, this patient’s LDL is 155 mg/dL.

Epidemiologic studies indicate a direct association between serum cholesterol levels and rate of coronary heart disease and an indirect relation to HDL.

Atherosclerotic vascular disease may manifest in any of a variety of ways including: coronary heart disease, cerebrovascular disease and peripheral vascular disease.

The common lipid disorders can be grouped into isolated hypercholesterolemia (II a ), isolated hypertriglyceridemia (I, IV, V) and combined hypercholesterolemia and hypertriglyceridemia (II b, III). This patient’s lipid profile most closely fits the Fredrickson phenotype IIb, or familial combined hyperlipidemia. This conclusion is based on the patient’s marked elevation of both total cholesterol and triglycerides. The triglyceride level less than 1000 mg/dL effectively excludes familial lipoprotein hyperlipidemia, that is, Fredrickson phenotype V.

Hypothyroidism is a common cause of hyperlipidemia.  Hypertriglyceridemia accompanies chronic renal failure in about 50% of patients.  Nephrotic syndrome, without renal failure, is associated with an elevation in LDL cholesterol.

Mr. Martin needs an aggressive program to modify his risks for atherosclerotic vascular disease, in particular his risks for coronary heart disease (tobacco use, HTN, lipid disorder, overweight and inactivity).

• Reduce intake of saturated fat (<7% of total calories) and cholesterol (<200 mg/day)
• Include LDL lowering foods to diet such as plant stanols/sterols (2 g/day) and viscous (soluble) fiber (10-25 g/day)
• Losing weight
• Increasing exercise

You begin with extensive counseling about adopting a daily exercise routine and making changes to his diet in accordance with the National Cholesterol Education Program (NCEP) as a means to both weight and cholesterol reduction.  You also suggest frequent monitoring of his high blood pressure and decreasing the amount of sodium in his diet.

You counsel him on smoking cessation.

On his return visit one month later he is very pleased about his weight loss of 5 lbs, confirmed by your office scale.  Unfortunately, his blood pressure is 169/99 mmHg.  On a blood pressure check in the office two weeks ago, his blood pressure was 172/95 mmHg. While strongly encouraging continuing weight reduction and lifestyle modification, you elect to begin pharmacological treatment of his hypertension.  (Please refer to the computer case on HTN for more detailed discussion on treatment of HTN).  As part of his work up for HTN, UA and creatinine were checked.  Both were normal.

• Diuretics commonly increase both LDL cholesterol and triglycerides. 
• Beta-blockers, particularly β1 selective agents, increase triglycerides and decrease HDL cholesterol. 
• Other medications can also adversely affect lipid profiles.  These include such commonly used medications such as corticosteriods and high dose estrogens.  Cholestyramine may raise triglycerides while lowering LDL cholesterol.

You started him on enalapril and ask him to return for blood pressure check with the nurse.  After 5 months the patient returns for a follow-up visit with 3 consecutive blood pressures below 135/80 taken on separate occasions.  He has no complaints about his medication.  He has lost 20 lbs since his first appointment with you. 

LDL goals and treatment decisions are based on risk assessment of the patient and screening LDL levels. Six months after instituting lifestyle changes the lipid profile should be reassessed. If the LDL cholesterol goals are not obtained then drug therapy should be initiated.

*CHD risk equivalent includes diabetes, clinical forms of atherosclerotic disease (peripheral artery disease, abdominal aortic aneurysm, symptomatic carotid artery disease) and a 10 year risk for CHD that exceeds 20%. 

Adapted from the National Cholesterol Education Program 3nd Report of the Expert Panel on the Detection, Evaluation and Treatment of High Blood Cholesterol in Adults.1

• Cigarette smoking
• Hypertension (BP > 140/90 mmHg or on antihypertensive medication)
• Low HDL (<40 mg/dL)
• Family history of premature CHD (First degree male age <55; First degree female age <65)
• Age (Men >45; Women > 55)

Note: HDL cholesterol >60 counts as a negative risk factor and removes one risk factor from the total count. 

10-year-risk assessment is done using the Framingham risk score. This calculation incorporates age, total cholesterol, HDL cholesterol, systolic blood pressure, treatment for hypertension, and cigarette smoking. Each parameter is assigned a point score and the total sum is associated with a percent risk of developing CHD within 10 years.

The patient’s fasting lipid profile is repeated. Despite his lifestyle changes his LDL level is now 165.

Despite a marked improvement in the patient’s lipid profile, he has an LDL cholesterol calculated to be 165 mg/dL. Based on the recommendations of the National Cholesterol Education Program, drug therapy should be initiated for a persistent LDL cholesterol greater than 160 mg/dL in a patient with 2 or more risk factors for coronary heart disease. The goal LDL cholesterol with therapy and a continued lifestyle changes is < 130 mg/dL.

Currently, there are 5 classes of agents available for the treatment of dyslipidemia: 

1. HMG-CoA reductase inhibitors (pravastatin, simvastatin, lovastatin, atorvastatin)
2. Bile acid sequestrants (cholestyramine, colesevelam, colestipol)
3. Nicotinic acid (Niacin)
4. Fibric acid derivatives (Gemfibrozil)
5. Ezetimibe (Zetia, Vytorin, Ezetrol)

HMG-CoA reductase inhibitors (Statins) are first line medications for most patients with hypercholesterolemia.

After continuing discussion with the patient about the need for pharmacological therapy, you prescribe pravastatin.

Headache, nausea and myositis may result from the use of HMG-CoA reductase inhibitors. However, these agents are generally much better tolerated than nicotinic acid.

Baseline liver function tests should be obtained prior to the initiation of therapy with an HMG-CoA reductase inhibitor and repeated in 6 weeks, then every 3months for 1 year, then every 6 months for an additional year, and then yearly there after. These agents may elevate liver function tests necessitating discontinuation of the drug. Lipid profiles should be obtained at the same intervals.

Nicotinic acid (Niacin) helps to increase HDL by 15-35%. The most common side effect of this medication is flushing which can be prevented by taking aspirin prior to taking the Niacin. Other side effects include hyperglycemia and hyperuricemia thus, it should be used with caution in patients with gout.

Bile acid sequestrants bind bile acids in the intestine allowing them to pass into the stool instead of being reabsorbed.  This lack of reabsorption from the gut increases the liver’s production of bile acid to replace the bile acid lost in the stool.  The liver converts more cholesterol into bile acids thus lowering the level of LDL in the blood. 

Because more bound bile acids are excreted in the stool, the most common side effects include GI symptoms such as constipation, bloating, excess gas and abdominal pain.

Six months later Mr. Martin returns for a routine evaluation.  He is tolerating pravastatin without difficulty.

The patient’s fasting lipid profile is repeated:

• Total cholesterol = 180 mg/dL
• Triglycerides = 150 mg/dL
• HDL = 30 mg/dL

You commend the patient on his continued weight loss and the marked improvement in his lipid profile, noting an LDL cholesterol of 120 mg/dL.

Gemfibrozil is a lipoprotein lipase stimulator which acts by increasing VLDL and triglyceride catabolism. This essentially increases lipid HDL and decreases triglycerides. It is most commonly indicated with triglyceride concentrations > 2000 mg/dL. The most common side effect is GI upset.

Mr. Martin’s use of tobacco remains a substantial modifiable risk factor for coronary heart disease. You advise Mr. Martin to truly focus his effort on smoking cessation.