Triglycerides, VLDL Size, IDL Particle Number Tied to Ischemic Stroke

A prospective case-control study found that among a panel of lipid and lipoprotein biomarkers, baseline triglycerides, very low-density lipoprotein (VLDL) size, and intermediate-density lipoprotein (IDL) particle number were significantly associated with ischemic stroke in postmenopausal women (Stroke 2012; doi:10.1161/STROKEAHA.111.641324). If confirmed in other studies, the findings could be used to test whether lifestyle modification and/or medications are warranted to reduce the risk of ischemic stroke in this population.

The study involved a subset of 972 ischemic stroke subjects and 972 matched controls from the Women’s Health Initiative Observational Study, which was designed to explore the effect of numerous factors on many of the major causes of morbidity and mortality in postmenopausal women. Participants all were postmenopausal and 50-79 years at baseline, and were followed for a mean of 7.9 years. Ischemic stroke, defined as rapid onset of a persistent neurological deficit caused by an obstruction lasting more than 24 hours, was the primary outcome.

After a series of analyses the researchers found that with the exception of triglycerides, VLDL size, and IDL particle number, associations between numerous lipid and lipoprotein biomarkers and risk of stroke were markedly attenuated after adjustment for cardiovascular risk factors. According to the authors, their findings suggest that lipid and lipoprotein abnormalities may play a larger role in the risk of ischemic stroke than traditional lipid testing indicates. The investigators also found that while there was not a significant association between the biomarkers in question and hormone therapy use, the association between several markers and stroke were greater in the group not on hormone therapy.

TSH Levels within the Reference Range Still Pose Risks

A long-term study of more than 15,000 adults found that thyroid stimulating hormone (TSH) levels within the reference range are positively and strongly associated with the risk of future hypothyroidism (J Clin Endocrinol Metab 2012;97:93–99). Likewise, TSH concentrations at the lower limit of the reference range may be associated with increased risk of hyperthyroidism.

The investigators conducted the study to build on prior research that showed an increased risk of hypothyroidism in people with high, but within the reference range, levels of serum TSH. Compared with these studies, the authors’ findings are based on a larger population, which gave more precise risk estimates across the TSH reference range for both men and women.

The study involved 10,083 women and 5,023 men without previous thyroid disease, who had baseline TSH levels between 0.20-4.5 mU/L and who participated in a follow-up visit a median of 11 years later. In all, 3.5% of women and 1.3% of men developed hypothyroidism during the study, while 1.1% of women and 0.6% of men developed hyperthyroidism. Baseline TSH levels were positively associated with risk of developing hypothyroidism, with risk rising with higher baseline TSH levels. Similarly, the risk of hyperthyroidism was higher in women with lower baseline levels of TSH. However, the low number of hyperthyroid men precluded precise estimates of risk associated with baseline TSH and hyperthyroidism for that population.

Because of the observed increased risk of hypothyroidism in patients with TSH levels in the upper part of reference range, some have suggested that the TSH reference range should be lowered. However, the authors found that the risk of hypothyroidism appears to be gradual across the reference range, with no clear cutoff point. They suggested instead that for individuals with TSH values in the uppermost part of the reference range, follow-up thyroid function testing may be warranted.

Chronic Hyperglycemia Linked to Subclinical Coronary Heart Disease

Chronic hyperglycemia is independently associated with subclinical myocardial injury, identified through elevated levels of cardiac troponin T (cTn T) (J Am Coll Cardiol 2012;59:484–9). The association, which existed in both diabetics and non-diabetics, suggests that hyperglycemia contributes to myocardial injury beyond its role in the development of atherosclerosis.

HbA1c as a marker of chronic hyperglycemia has been associated with incident coronary heart disease (CHD) and all-cause mortality, but much less is known about any relationship between HbA1c and subclinical CHD. cTn T also has been independently associated with CHD. The availability of a novel high sensitivity-cTn T assay made it possible for the authors to evaluate whether HbA1c levels would be associated with subclinical myocardial injury measured by elevated cTn T concentrations.

The study involved nearly 10,000 participants without CHD in the Atherosclerosis Risk in Communities Study, a prospective epidemiologic study investigating atherosclerotic disease and risk factors in four cities. The hs-cTn T assay used in the study has a lower limit of detection of 3.0 ng/L; the investigators defined elevated cTn T as levels >14 ng/L, the previously reported 99th percentile value in a healthy population.

The researchers found that baseline HbA1c was positively associated with cTn T in a linear relationship. Compared to subjects with HbA1c values <5.7%, cTn T values were approximately 25% higher in those with HbA1c levels between 5.7–6.4%, and 70% higher among participants with HbA1c ≥6.5%. Overall, 7.3% of subjects had elevated cTn T values; the corresponding percentages for those with and without diabetes were 21.8% and 6.3%, respectively. After adjusting for traditional risk factors, the authors found that in comparison to individuals with HbA1c <5.7%, the odds ratios for elevated cTn T for those with HbA1c levels 5.7–6.4% and ≥6.5% were 1.26 and 1.97, respectively.

New Testing Paradigm Proposed for Primary Aldosteronism

A study evaluating the role of serum 18-hydroxycorticosterone (s18OHB), urinary and serum 18-hydroxycortisol (u- and s18OHF), and urinary and serum 18-oxocortisol (u- and s18oxof) in the diagnosis of primary aldosteronism (PA) and its subtypes found that s18OHB, u18OHF, and u18oxoF measurements correlate with existing PA confirmatory tests (J Clin Endocrinol Metab 2012;97:881–89). If verified in other studies, the findings could lead to changes in confirmatory testing and/or adrenal vein sampling (AVS) strategies in a sizable number of patients.

PA diagnostic guidelines call for positive PA screening test results, aldosterone/plasma renin activity ratio (ARR), to be followed by a confirmatory test and further CT scanning and AVS. However, there is no agreement on which of four accepted confirmatory tests should be performed, because each has pros and cons. AVS is the gold standard method for differentiating unilateral from bilateral PA, but is costly and is not available in most hospitals, according to the authors. This led the researchers to evaluate whether 18OHB and the hybrid steroids, 18OHF and 18oxoF, with characteristics of both cortisol and aldosterone, might identify and distinguish PA from its subtypes.

The study involved 143 hypertensive patients with positive ARR results and aldosterone levels >15 ng/dL. While 62 patients had low-renin essential hypertension, the remainder had PA. u18OHF was the most useful test in differentiating between essential hypertension and PA, and the researchers found that use of this test would have avoided more than one-third of IV salt loading confirmatory tests and 7% of AVS in the study population. They proposed a 24-hour u18OHF cutoff of <130 µg/day to rule-out PA.

PSA Velocity Risk Count Improves Specificity of Prostate Cancer Screening

Prostate-specific antigen (PSA) velocity risk count significantly improves the specificity of screening for prostate cancer (BJU Int 2012; 4:508–13). Using this metric could be useful in reducing unnecessary biopsies in comparison to PSA alone.

The authors defined PSA velocity risk count as the number of serial PSA measurements exceeding 0.4 ng/mL per year. Conflicting results from large scale clinical trials about the pros and cons of both PSA and of PSA velocity prompted the researchers to explore this metric.

The study involved 18,214 participants who underwent PSA testing and digital rectal examination at 6–12 month intervals. Overall, 1,125 subsequently were diagnosed with prostate cancer. After a series of statistical analyses, the authors found that compared with men who had PSA velocity risk counts ≤1, those with a risk count of 2 had an 8-fold increased risk of prostate cancer and a 5.4-fold increased risk of Gleason scores of 8–10 on biopsy.