The causes of the lipid disorders in patients referred to specialty clinics for difficult-to-treat dyslipidemias are likely multifactorial. However, the importance of evaluating for secondary causes is unclear. The investigators performed a chart review of new patients referred to the University of Michigan Lipid Clinic from January 2004 to June 2011 (n = 824) to evaluate for the prevalence of several secondary causes of dyslipidemia. In addition to lipoproteins, new patients were assessed for secondary dyslipidemias by a standardized protocol consisting of laboratory testing, a nutritional evaluation, and medical history. These data were evaluated to determine the prevalence of several secondary causes of dyslipidemia. A total of 363 separate factors were identified in the 824 patients that were thought to be potential secondary causes of dyslipidemia. Because some patients (n = 83 [10%]) had multiple conditions, there were 230 (28% of the cohort) with ≥1 potential secondary dyslipidemias. The most common conditions were excessive alcohol intake (n = 82 [10%]), uncontrolled diabetes mellitus (n = 68 [8%]), and overt albuminuria. Although other causes occurred less frequently (each individually found in <5% of patients), altogether they were present in a substantial portion of patients (n = 102 [12%]). In conclusion, nearly 1/3 of patients referred to a specialty clinic had identifiable secondary conditions plausibly contributing to their dyslipidemia. Numerous disorders were identified, with diabetes mellitus and excessive alcohol being the most common.
Current guidelines for hyperlipidemia state that clinicians should evaluate for underlying conditions that could be causing or exacerbating dyslipidemias before initiating or intensifying treatment in their patients. These conditions are referred to as “secondary causes” of dyslipidemia and are important to identify for several reasons. Some associated diseases are important health issues to recognize per se (e.g., chronic kidney disease, diabetes mellitus [DM]), and the dyslipidemia may be 1 of the first clues to the diagnosis. Treatment of the underlying condition may also improve the dyslipidemia, potentially reducing the need for therapy. Recognizing the co-morbidity may alter subsequent treatment decisions (e.g., identifying potential drug interactions, diagnosing hypothyroidism, which may increase the risk for statin-related myopathy). Finally, some dyslipidemias can appear to be refractory to drug treatment in the presence of an ongoing unrecognized secondary cause. For example, untreated DM or excessive alcohol intake can render medical therapy of hypertriglyceridemia much less effective. Although numerous factors have been linked to adverse lipoprotein changes, their prevalence and clinical importance remain poorly described. Hence, we evaluated the characteristics of secondary causes of dyslipidemia in patients referred to our lipid clinic.
Methods
This study was approved by the University of Michigan institutional review board. We performed a retrospective chart review of the electronic medical records of all patients referred to the tertiary care lipid management clinic at the University of Michigan from January 2004 to June 2011. As part of the initial visit, patients were seen by a dietician for nutrition assessment. In addition, laboratory testing was performed to assess lipoproteins, cardiovascular risk factors and a standard screening protocol for secondary dyslipidemias. Afterward, the patients were evaluated by 1 of 2 physicians specializing in the treatment of complex lipid disorders.
Patient information from the dietician, physician history, and initial visit laboratory was entered into a database ( Table 1 ). The results were checked by 1 of the physicians for accuracy. The presence of a specific set of secondary causes of dyslipidemia was evaluated for in each patient from a list of factors that were uniformly measured on all patients during laboratory testing or assessed on first dietician and physician visits (disorders listed in Table 2 ). Next, we determined if the disorder was an “active condition,” defined as being present by self-report or associated with pertinent laboratory abnormalities at the first visit as defined in Table 2 . Thereafter, it was assessed if the active condition was contributing to the related dyslipidemia (i.e., a “true secondary dyslipidemia”). This scenario was met when the active condition was associated with lipid abnormalities, either an elevation in triglycerides >150 mg/dl or low-density lipoprotein cholesterol >130 mg/dl alone or together, in a manner known to be induced by the specific disorder.
| Variable | Total Patients |
|---|---|
| (n = 824) | |
| Age (years) | 52 ± 14 |
| Men | 460 (56%) |
| Race/ethnicity | |
| Asian | 36 (4%) |
| African American | 45 (5%) |
| Caucasian | 692 (84%) |
| Hispanic | 11 (1%) |
| Native American | 1 (<1%) |
| Multiple race | 2 (<1%) |
| Unknown or not reported | 32 (4%) |
| Systolic blood pressure (mm Hg) | 117 ± 16 |
| Diastolic blood pressure (mm Hg) | 69 ± 10 |
| Body mass index (kg/m 2 ) | 29.64 ± 6.26 |
| Current smokers (any cigarettes in past month) | 97 (12%) |
| Previous smokers (no cigarettes in past month) | 282 (34%) |
| Family history of early coronary heart disease | 297 (36%) |
| Personal history of coronary heart disease | 220 (27%) |
| Triglycerides (mg/dl) | 304 ± 462 |
| Total cholesterol (mg/dl) | 242 ± 82 |
| High-density lipoprotein-cholesterol (mg/dl) | 44 ± 19 |
| Low-density lipoprotein-cholesterol (mg/dl) | 144 ± 67 |
| Total cholesterol/high-density lipoprotein cholesterol (mg/dl) | 6.3 ± 4 |
| Non-high-density lipoprotein cholesterol (mg/dl) | 197 ± 80 |
| Lipoprotein(a) (mg/dl) | 37 ± 43 |
| Apolipoprotein A (mg/dl) | 140 ± 35 |
| Apolipoprotein B (mg/dl) | 118 ± 38 |
| Medications | |
| Statins | 32% |
| Ezetimibe | 14% |
| Niacin | 12% |
| Bile acid resin | 4% |
| Fibrates | 17% |
| Fish oil | 34% |
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