Presence or Absence of ApoC-III has Opposite Associations for CHD Risk

Harvard University researchers recently reported that the presence or absence of apolipoprotein C-III (apoC-III) on the surface of high-density lipoprotein cholesterol (HDL-C) particles had opposite associations with risk of future coronary heart disease (CHD) (J Am Heart Assoc 2012;1:e000232). The findings highlight that HDL-C comprises a group of particles that may be more or less closely linked with atherosclerosis, and a factor that could have implications for the development of novel therapeutic interventions aimed at raising HDL-C to reduce CHD risk.

The authors explored this issue based on their own prior research showing that apoC-III provokes inflammatory and atherogenic responses in cells that are involved in atherosclerosis, and on conflicting findings by other investigators about the benefits of raising HDL-C levels.

The study involved 634 cases and 637 controls from two longitudinal studies in which the subjects gave baseline blood samples and were then followed via biennial questionnaires thereafter for 10–14 years In all, there were 634 incident CHD cases documented.

The researchers found that overall, the relative risk of CHD per each standard deviation of total HDL-C was 0.78. However, HDL-C without apoC-III was associated with reduced risk of CHD, while HDL-C with apoC-III was associated with increased risk. Adjusting for triglycerides and apoB attenuated the risks, but the two HDL-C subgroups remained differentially associated with CHD risk.

Changes Over Time in eGFR Likely Due to Changes in Measured GFR, not Errors in eGFR

Pooled data from four clinical trials with longitudinal measurements of glomerular filtration rates (GFR) and serum creatinine showed that the accuracy of GFR estimates did not change over time (Am J Kidney Dis 2012 doi:10.1053/j.ajkd.2012.01.024). The findings suggest that clinicians should interpret changes over time in estimated GFR (eGFR) in most individuals as reflecting changes in measured GFR rather than as errors in eGFR.

The authors examined this issue because filtration markers like creatinine, which are used to estimate GFR, are affected by physiological processes other than GFR, which can lead to errors in eGFR. They pooled data from four trials involving 3,531 participants that were part of the Chronic Kidney Disease Epidemiological Collaboration (CKD-EPI). In all, the investigators accessed 19,735 GFR measurements collected during a mean follow-up of 2.5 years. At baseline the mean values for measured and eGFR were 73.1 mL/min/1.73 m2 and 72.7 mL/min/1.73 m2, respectively. Only 15% of subjects had a change > ±3 mL/min/1.73 m2 irrespective of baseline GFR, and just 2% had a change in error >5%.

These findings show that error in GFR estimates generally is stable over time, with just 2–15% of changes in error large enough to be clinically significant. However, clinicians should consider measuring GFR as a confirmatory test if more accurate information would improve clinical decision-making.

Fetuin-A Increases CVD Risk in Non-Diabetics; Decreases Risk in Diabetics

Fetuin-A levels are independently associated with increased risk of cardiovascular disease (CVD) mortality in adults older than age 50 without diabetes, but with reduced risk of CVD in those who have diabetes (J Am Coll Cardiol 2012;59:1688–96). The findings suggest that the relationship between fetuin-A and cardiovascular health is more complex than previously thought, according to the authors.

The investigators were interested in exploring the relationship between fetuin-A and CVD based on the current understanding of the physiological functions of this multi-functional liver-derived protein.

The study involved 1,688 adults enrolled in the Rancho Bernardo Study who participated in the 1992 and 1996 clinic visits associated with this long-term study of CVD risk factors. During the median 12-year follow-up, 273 deaths were attributed to CVD.

The researchers observed a striking difference in the association of fetuin-A and CVD mortality risk based on diabetes status. Low levels were associated with a 76% higher risk of CVD death in individuals without diabetes, but with a 57% lower risk in those with diabetes. Both these associations were statistically significantly and independent of traditional CVD risk factors, insulin resistance, and measures of liver and kidney function. Based on these findings the authors called for further studies with larger populations to determine whether fetuin-A is a useful CVD risk stratification criteria.

Both Universal, Risk-Based Screening for Autoimmune Thyroid Disease in Pregnancy Cost-Effective

A comparison of three strategies for screening women for autoimmune thyroid disease (AITD) in the first trimester of pregnancy found universal screening to be cost-effective in comparison to both no screening and screening high-risk women only (J Clin Endocrinol Metabl 2012;97:1536–46). The findings should prompt the medical community to seriously consider screening all pregnant women for AITD, according to the authors.

The researchers sought to examine this issue because AITD-related hypothyroidism in pregnancy has been associated with adverse maternal and fetal outcomes. However, professional societies have endorsed either universal screening of pregnant women, or selective screening for those at high-risk of thyroid dysfunction, which may miss 30–50% of cases.

The authors developed a decision model to analyze differences in costs and health benefits among the three screening strategies. They assumed women would be screened with serum thyroid-stimulating hormone (TSH) and anti-thyroid perioxidase (anti-TPO) antibody tests during their first prenatal visit between 6–12 weeks’ gestation, and that those who screened positive would undergo further testing, follow-up, and treatment. Women with TSH levels >5 mIU/L would be tested for total T4 (TT4) levels regardless of their anti-TPO antibody status, and they would be treated for either overt or subclinical hypothyroidism depending on their TT4 results, with repeat testing at prescribed intervals in the first year post-partum and thereafter.

The researchers found that in comparison to no screening, both risk-based and universal screening strategies would be cost-effective, with incremental cost-effectiveness ratios (ICER) of $6,753 and $7,138 per quality adjusted life year (QALY), respectively. Universal screening also was cost-effective compared with risk-based screening, with an ICER of $7,258 per QALY.