James J. Maciejko

The effect of freezing and long-term storage on the stability of cardiac troponin T.

Cardiac troponin T (cTnT) levels are widely used to assess for evidence of myocardial infarction. We studied the effect of freezing and long-term storage on the stability of cTnT in blood samples from 178 patients with end-stage renal failure. The serum was separated and divided into multiple aliquots. Baseline cTnT levels were measured in the unfrozen aliquots. The remaining aliquots were frozen using standard techniques. The aliquots were thawed after 3, 6, 12, or 24 months and cTnT levels measured. There were no significant changes in the mean +/- SEM cTnT levels up to 12 months (0.111 +/- 0.098 microg/L) compared with baseline (0.114 +/- 0.098 microg/L); after 24 months, cTnT levels were significantly lower (0.107 +/- 0.095 microg/L) than baseline ( P = .004). The cTnT assay is a reliable method of measuring the cTnT level in human serum up to 12 months of frozen storage. However, after 24 months, the cTnT level was 0.007 microg/L lower than baseline, potentially causing erroneous interpretations. The clinical significance of the change in the cTnT level after long-term frozen storage is unclear. Further studies, including prospective analysis of patient outcomes, should be helpful.

Efficacy and Safety of Pravastatin in the Long-term Treatment of Elderly Patients With Hypercholesterolemia

PURPOSE Elevated cholesterol levels are a major risk factor for coronary heart disease, which remains a significant problem in patients beyond age 65 years. Because drug therapy for the control of hypercholesterolemia in elderly patients is frequently considered to be indicated, we investigated the efficacy and safety of pravastatin in the treatment of elderly subjects with primary hypercholesterolemia. PATIENTS AND METHODS In this 96-week, multicenter, double-blind, placebo-controlled study, 142 subjects (95 women, 47 men) 64 to 90 years of age with elevated cholesterol levels despite dietary intervention were randomized to receive pravastatin 20 mg at bedtime or matching placebo (2:1). Dosage could be doubled after 8 weeks, a bile acid-binding resin could be added after 16 weeks, and nicotinic acid or probucol could be added after 32 weeks, as needed, to adequately lower the low-density lipoprotein cholesterol (LDL-C) levels. RESULTS Significant reductions in the levels of LDL-C (-30.9%), total cholesterol (Total-C; -21.9%), and triglycerides (TG; -16.7%) and significant increases in the levels of high-density lipoprotein cholesterol (HDL-C; 11.3%) were noted in the group receiving pravastatin treatment at 16 weeks (P < or = 0.001 compared with baseline, P < or = 0.01 compared with placebo). The cholesterol-lowering effects of pravastatin were sustained throughout the 96 weeks of the trial. Pravastatin was well tolerated, with an overall incidence of adverse events nearly identical to that of placebo. CONCLUSIONS In this study, pravastatin was well tolerated and effective in lowering LDL-C, Total-C, and TG and in raising HDL-C during long-term treatment of elderly patients with primary hypercholesterolemia.

The impact of coronary artery disease risk factors on intravascular ultrasound-derived morphologic indices of human coronaries.

Objective: The relationship of intravascular ultrasound (IVUS)‐derived measurements of atherosclerotic plaque to various coronary artery disease (CAD) risk factors is not well known. The purpose of this study was to examine the relationship of percent coronary luminal stenosis by IVUS to other IVUS measures of CAD, as well as the relationship of common IVUS measures of CAD to traditional CAD risk factors. We hypothesized that one or more IVUS measures of CAD might relate more strongly to CAD risk factors than does percent luminal coronary stenosis. Methods: The records of 897 consecutive patients (57% men, mean age 62 years) who underwent IVUS investigation of their coronary arteries from 1996 through 2001 were retrospectively reviewed. IVUS was performed using a 20‐MHz probe (Jomed, Rancho Cordoba, CA) and a manual pull‐back technique to image the coronary arteries. Coronary artery remodeling ratio—i.e., the ratio of coronary lesion external elastic membrane cross‐sectional area (EEM CSA) to proximal reference artery EEM CSA; plaque burden—i.e., plaque plus media CSA divided by EEM CSA; calcium arc; and percent stenosis of luminal cross‐sectional area were measured by a single reader. Results: Percent area stenosis, the most commonly used IVUS parameter, did not correlate with the other three IVUS‐derived parameters, nor was it related to any of the CAD risk factors considered. In contrast, remodeling ratio was directly correlated with plaque burden (r = 0.22, P < 0.001), but inversely related to calcium arc (r =−0.13, P = 0.01). IVUS plaque burden was significantly correlated with male gender (P < 0.0001) and diabetes mellitus (DM) (P = 0.003). In multivariate analyses including age, gender, and CAD risk factors, plaque burden was significantly associated with age, male gender, and DM, but not with chronic renal failure, hypertension, or hypercholesterolemia. The multivariate model also revealed that the calcium arc was significantly associated with male gender and age. These IVUS findings provide anatomic documentation that the traditional CAD risk factors relate more strongly to plaque burden than to percent coronary arterial luminal narrowing.

Lysosomal acid lipase deficiency in all siblings of the same parents

We present 4 normal-weight sibling children with lysosomal acid lipase deficiency (LAL-D). LAL-D was considered in the differential diagnosis based on the absence of secondary causes and primary inherited traits for their marked hyperlipidemia, together with unexplained hepatic transaminase elevation. Residual lysosomal acid lipase activity confirmed the diagnosis. DNA sequencing of LIPA indicated that the siblings were compound heterozygotes (c.894G>A and c.428+1G>A). This case describes the unusual occurrence of all offspring from the same nonconsanguineous mother and father inheriting compound heterozygosity of a recessive trait and the identification of an apparently unique LIPA mutation (c.428+1G>A). It highlights the collaborative effort between a lipidologist and gastroenterologist in developing a differential diagnosis leading to the confirmatory diagnosis of this rare, life-threatening disease. With the availability of an effective enzyme replacement therapy (sebelipase alfa), LAL-D should be entertained in the differential diagnosis of children, adolescents, and young adults with idiopathic hyperlipidemia and unexplained hepatic transaminase elevation.

The Sweet Spot: Continued Search for the Glycemic Threshold for Macrovascular Disease—A Retrospective Single Center Experience

Background. Atherosclerotic cardiovascular disease (ASCVD) is a common complication of diabetes mellitus and impaired fasting glucose (IFG). We hypothesized that the relation of fasting glucose levels to ASCVD is linear, with the prevalence of clinical ASCVD beginning to increase even among individuals currently categorized as normoglycemic. Methods. Patient charts were retrospectively reviewed from our Dyslipidemic Preventive Cardiology Clinic. We evaluated the prevalence of ASCVD relative to fasting glucose levels in a cross-section of patients at high risk for ASCVD. Results. In 558 dyslipidemic patients, ASCVD prevalence increased with increasing fasting glucose levels. A significantly higher prevalence of ASCVD was observed among patients with fasting glucose levels between 90 and 99 mg/dL versus lower levels. As glucose levels increased from 90 to 125 mg/dL, the prevalence of ASCVD continued to rise in parallel. Logistic regression analysis with forward likelihood ratio stepwise selection indicated that individuals with fasting blood glucose of 90–99 mg/dL were 2.6 times more likely to have ASCVD than those with lower levels of fasting blood glucose. Conclusion. Our findings suggest that the current cutoff for impaired fasting glucose of 100 mg/dL may be somewhat conservative and that a level above 90 mg/dL may be more appropriate as an ASCVD risk factor, particularly in patients with a lipid disorder.