Case #343: Multiple Risk Factors

“Lauren,” a 52-year-old female, initially presented two years ago with high blood pressure, osteoarthritis, migraine headaches, metabolic syndrome, dyslipidemia and hypothyroidism. Her family history includes a grandfather who suffered a stroke and her mother with type 2 diabetes and hypertension. Her sister currently has hypertension.

Her NCEP risk factors included HDLc < 40 and HTN (146/86), placing her in the moderate risk category (two of five risk factors). The patient’s Framingham risk score on her first visit in 2008 (age 50), however, was only 1 percent, which placed her in the low 10-year-risk category. She is a nonsmoker, rare exerciser and rare alcohol drinker.

The patient is now on ramipril 10 mg at night for blood pressure (BP = 112/72), and metformin (1000 mg/day) was started to address the metabolic syndrome and levothyroxine 100 mcg/day to address hypothyroidism. Her BMI is over 35, her waist is over 35 inches and lifestyle changes have been encouraged.

Mean CIMT/CUS in October 2008 was 0.578 mm, which was low risk for her age, and no plaque was detected. The vascular carotid technician did note thickening of the right carotid bulb, however.

CIMT/CUS was repeated in October 2010 showing a mean CIMT of 0.594 mm, which is again low risk for her age. However, bilateral atheroma was noted in the right bulb measurement of 1.9 mm of heterogeneous plaque and left bulb measurement of 1.3 mm of heterogeneous plaque. The patient now demonstrates several risk factors plus measurable plaque.

Labs – Click here to view Lauren’s VAP Test results and appropriate reference ranges from Atherotech

Lab Results
September 2008: The patient’s low HDLc stands out, although her overall lipids look good and CIMT/CUS is normal. The patient’s thyroid test was also in the normal range on 100 mcg of levothyroxine.

September 2009: SLP shows no remarkable change in TC, LDLc or TC/HDL ratio. Triglycerides are now just above the desirable range at 162. Metabolic syndrome was noted and Lauren was again encouraged to begin lifestyle changes. No change in her medications was prescribed.

September 2010: The VAP ultracentrifuge expanded lipid profile and other labs were drawn and sent to Atherotech. Several issues were noted with this more comprehensive lab testing:

• Metabolic lipids are again noted as a concern.
• She shows dense phenotype lipids with high LDL_3-4 (dense pattern), high VLDL₃ remnant (dense) and again low HDL, HDL₂ and HDL₃.
• While sugars have supported metabolic syndrome and impaired fasting glucose, Lauren’s glucose this year (non-fasting) was markedly elevated and her A1c = 6.4% suggests high risk for type 2 diabetes mellitus despite being on 1000 mg/day of metformin for the last two years.
• ApoB = 104, which indicates moderate risk.
• The ApoA1 measurement of 111 represents very high risk.
• LDL density pattern is of great concern. Dense phenotypic LDL has been implicated in several studies to raise risk for atherosclerosis and events.
• Hs-CRP is high at 3.4. In the JUPITER trial, elevated hs-CRP predicted higher risk and residual risk, even with optimal LDL levels on therapy.
• Vitamin D level is “very low.” A DEXA scan was ordered and aggressive therapy prescribed. Many studies have linked low Vitamin D with higher morbidity and mortality, and symptomatic osteomalacia should be targeted with treatment. Our practice treats all vitamin D’s that are insufficient.

Discussion
To treat or not to treat? How aggressively — if at all — should this patient’s HDLc have been treated in 2008 and 2009? Some would argue that the patient was at her lipid goals, and in that case HDLc didn’t matter.

Based on her age, low-risk Framingham score and “normal” CIMT/CUS in 2008, we opted not to treat and did not perform any inflammatory testing (e.g., hs-CRP, Lp-PLA₂) or expanded lipid testing (e.g., ultracentrifuge or spectroscopy) at that time.

The presence of metabolic syndrome (prediabetes) for the last two years and her family history of diabetes, hypertension and stroke have not convinced her to adopt healthy lifestyle changes. Lauren is adherent to hypertension prescription therapy and her standard lipid panels in 2008 and 2009 are debatable in terms of starting prescription lipid management based on age and risk.

However, I now think of this patient as the “vascular soufflé.” She has glucose abnormalities preprandial and postprandial, and metabolic waist along with dense phenotype lipids. The new presence of atheroma in 2010 was both an eye opener for her clinician (me) and herself. New information from Lauren’s VAP UC lipid panel showed dense LDL, remnant VLDL₃ (dense, the majority of her VLDL), high ApoB, low ApoA1, low HDL and low HDL_2-3, suggesting a high degree of lipid pathophysiology.

In the Patient’s Terms
I arranged for Lauren to see a nutritionist and started her on a low-calorie, reduced simple carbohydrate diet (more protein, healthy fats and complex fiber carbohydrates) and daily exercise. I let the patient know that she was doing a good job of taking her high blood pressure medication, but the buildup of plaque in her carotid arteries (hardening of the arteries) was certainly of concern and something we could try and correct. Therefore, I was going to start her on medication to help her meet her cholesterol goals and get her into a lower risk category.

Based on her imaging and family history of risk as well as her abnormal lipid profile noted on the VAP lipid test, we decided that she would be an appropriate candidate for lipid prescription therapy in addition to lifestyle changes.

Lauren has been started on dual lipid therapy for her mixed dyslipidemia. Vitamin D therapy was also prescribed. She was scheduled to receive a repeat VAP lipid and glucose testing in 12 weeks.

–MC

Abbreviations
NCEP =  National Cholesterol Education Program
BMI =  Body Mass Index
CIMT/CUS = Carotid Intimal Medial Thickness/Carotid Ultrasound
HTN = Hypertension
SLP = Simple or Standard Lipid Panel
VAP = Vertical Auto Profile