Clinical Briefs

By Louis Kuritzky, MD

Thyroid Status, Disability and Cognitive Function, and Survival in Old Age

There is little disagreement about the merit of treating frank hypothyroidism. Because of conflicting data, much less consensus exists about whether subclinical hypothyroidism (ie, elevated TSH levels with normal T4) should be treated. Since thyroid disorders increase with age, a population of advanced years is an appropriate group in which to evaluate this issue further.

The Leiden 85-Plus Study is a prospective study of all individuals born in 1912-1914 living in Leiden, the Netherlands. Data was prospectively obtained from the entire population who agreed to be enrolled, without exclusions (n = 599), and these subjects were followed from age 85-89.

Outcome measures included cognitive function, degree of disability, depression, and overall mortality, each of which was assessed in relation to baseline and follow-up TSH and T4. The investigation uncovered 39 participants with previously undiagnosed overt hypothyroidism and 30 with undetected subclinical hypothyroidism. There were 2 new diagnoses of hyperthyroidism and 17 new diagnoses of subclinical hyperthyroidism (ie, decreased TSH with normal T4).

Thyroid status was not related to disability, depression, or cognitive function. However, the highest mortality was seen in those with a suppressed TSH level at baseline (subclinical hyperthyroidism). Somewhat surprisingly, subjects with elevations in TSH had the lowest mortality. Based upon these data, Gussekloo et al posit that thyroid replacement in subclinical hypothyroidism is unlikely to be beneficial; indeed, it could even be harmful.

Gussekloo J, et al. JAMA. 2004;292: 2591-2599.

Inflammatory Markers and the Risk of Coronary Heart Disease in Men and Women

Inflammatory markers have been consistently associated with coronary artery disease (CAD), the most thoroughly studied of which has been C-reactive protein (CRP). Since interleukin-6 (IL6) and tumor necrosis factor alpha (TNFa) are cytokines which induce CRP secretion, their status might also reflect CAD risk. TNFa is not as readily measurable as are its primary receptors, sTNF-R1 and sTNF-R2.

The Nurses Health Study (n = 121,700) and the Health Professionals Follow-up Study (n = 51,529) provided subjects who gave baseline blood samples, all of whom were free of known CAD at the time. Over approximately 8 years of follow-up, data from 515 men and women who had suffered an MI were compared with controls matched for age and smoking status.

Initial analysis indicated that increased levels of sTNF-R1 and sTNF-R2 were associated with CAD in women, but not men. However, after adjustment for other risk factors, only CRP remained a significant predictor of CAD. For instance, lower HDL levels were also associated with higher levels of inflammatory markers, and mitigated some of the predictive value of inflammatory markers.

CRP remains a consistent predictor of CAD risk.

Pai JK, et al N Engl J Med. 2004;351: 2599-2610.

Self-Measured Home Blood Pressure in Predicting Ambulatory Hypertension

Ambulatory blood pressure monitoring (ABPM) provides the best metric of overall blood pressure burden. Several factors have compromised use of ABPM as a primary metric in managing hypertension (HTN): its cost, inconvenience, relative lesser availability, and less frequent incorporation in major clinical trials than simple office blood pressure. Home blood pressure (HBP) is increasingly recognized as a valued measurement, especially when OBP is suspected of reflecting white coat hypertension, or when ABPM is not available.

This study evaluated the threshold of HBP that would capture 80% of persons who, as demonstrated by ABPM BP >135/85, have borderline or stage 1 HTN. Subjects (n = 48) who had demonstrated at least 2 elevated BP readings in an office setting underwent ABPM and HBP.

As has been repeatedly demonstrated in other trials, HBP correlated better with ABPM than OBP. The threshold of HBP, at which 80% of persons with HTN (as defined by ABPM >135/85) would be detected, was determined to be 125/76. Persons with HBP > 135/85 are designated as hypertensive. Those with HBP < 125/76 are considered normotensive (regardless of OBP measurement), and those between 125/76-135/85, being indeterminate, merit consideration of ABPM to further refine their burden of blood pressure.

Mansoor GA, et al. Am J Hypertens. 2004;17:1017-1022.

Dr. Kuritzky, Clinical Assistant Professor, University of Florida, Gainesville, is Associate Editor of Internal Medicine Alert.