Johan Sundsfjord

Serum TSH is positively associated with BMI.

Objective:To investigate whether there is an association between serum thyroid-stimulating hormone (TSH) within the normal range and body mass index (BMI).Design and subjects:The study was performed in 6164 subjects (2813 males) who attended the fifth Tromsø study in 2001, and in 1867 subjects (873 males) that attended both the fourth Tromsø study in 1994/1995 as well as the fifth Tromsø study.Measurements:Height, weight, and serum TSH were measured in all subjects, and smoking status was recorded.Results:Smokers and nonsmokers were analyzed separately. In the fifth Tromsø study, serum TSH was positively and significantly associated with BMI in the nonsmokers. Within the normal TSH range (defined as the 2.5–97.5 percentile), nonsmoking males in the highest TSH quartile had a mean BMI 0.4 kg/m2 higher compared to those in the lower quartile, whereas the difference for nonsmoking women was 1.4 kg/m2. Similarly, in nonsmokers in the longitudinal study, there was a significant and positive association between delta serum TSH (serum TSH in 2001 minus serum TSH in 1994) and delta BMI in those with serum TSH within the normal range both in 1994 and 2001. In these subjects, the quartile with the highest delta serum TSH had a mean increase in BMI from 1994 to 2001 that was 0.3 kg/m2 higher compared to those in the quartile with the lowest delta serum TSH. For the smokers, relations between serum TSH and BMI were not statistically significant.Conclusion:In nonsmokers there is a positive association between serum TSH within the normal range and BMI.

Waist circumference and testosterone levels in community dwelling men. The Tromsø study.

To examine the relationship of total and free testosterone and sex hormone-binding globulin (SHBG) with central obesity in men, we studied 1548 men aged 25–84 years that took part in the 1994–1995 survey of the Tromsø study. Total testosterone and SHBG were measured by immuno-assay and the free testosterone fraction was calculated. These measurements were analyzed in relation to anthropometric data and lifestyle factors. The age-adjusted correlation between waist circumference (WC) and total testosterone was −0.34 (p < 0.001), between WC and free testosterone −0.09 (p < 0.001) and, between WC and SHBG −0.44 (p < 0.001). Adjusting for BMI and lifestyle factors weakened, but did not eliminate these associations. All hormone and SHBG associations were stronger for WC than for waist-hip ratio or BMI. In age- and BMI-adjusted analyses men with a WC ≥ 102 cm had significantly lower levels of total testosterone and SHBG compared to men with an optimal WC, defined as < 94 cm (12.3 vs. 13.9 nmol/l; p < 0.01 and 48.5 vs. 55.1 nmol/l; p < 0.001, respectively). The lowest levels of total and free testosterone were observed in men with relatively high WC despite relatively low overall obesity (BMI), suggesting that WC should be the preferred anthropometric measurement in predicting endogenous testosterone levels.

Serum parathyroid hormone levels predict coronary heart disease: the Tromsø Study

Background Primary hyperparathyroidism (PHPT) is associated with hypertension, coronary atherosclerosis and other cardiovascular diseases. We aimed to evaluate serum parathyroid hormone (PTH) levels as an independent risk factor for coronary heart disease (CHD) in subjects with serum calcium within the reference range. Design Population-based cross-sectional study. Methods The Tromsø Study was attended by 27159 subjects aged 25-79 years. Serum PTH was measured in 3570 subjects. They all completed a questionnaire on medical history, including questions on angina pectoris and myocardial infarction along with a food-frequency questionnaire. A total of 1459 men and 1753 women with serum calcium 2.20-2.60 mmol/l, serum creatinine< 121 μmol/l and who did not use diuretics were included in the present study. Linear regression was used to reveal associations between PTH, age, body mass index, serum calcium, calcium intake, cholesterol, blood pressure, glycosylated haemoglobin (HbA1c) and smoking status. A logistic regression model was used to find the independent predictors of CHD. Results When stratified for age the rate of CHD was higher in the subjects with serum PTH > 6.8 pmol/l than in those with normal or low serum PTH levels [relative risk 1.67, 95% confidence interval (CI) 1.26-2.23 in men and 1.78, 95% CI 1.22-2.57 in women]. The highest PTH quartile (> 3.50 pmol/l in men and > 3.30 pmol/l in women) predicted CHD, with odds ratios of 1.70 (95% CI 1.08-2.70) for men and 1.73 (95% CI 1.04-2.88) for women, versus the lowest PTH quartile (< 1.90 pmol/l for men and < 1.80 pmol/l for women). Conclusions Serum PTH predicts CHD in subjects with calcium levels within the reference range. This may indicate a role for PTH in the development of CHD.

Serum Calcium and Cardiovascular Risk Factors and Diseases The Tromsø Study

Total serum calcium levels were measured in 12 865 men and 14 293 women, between the ages of 25 and 97 years, in the Tromsø Study during 1994 and 1995. With the use of a sex-specific multiple linear regression model with age, calcium, body mass index, cholesterol, HDL cholesterol, triglycerides, systolic and diastolic blood pressure, and pulse as possible covariates, serum calcium was significantly (P<0.001) and positively associated with systolic and diastolic blood pressure, serum cholesterol, and HDL cholesterol in both sexes. A similar but weaker association was observed between serum calcium and triglycerides in men (P<0.01). In all age groups, serum calcium levels were higher in men with a history of myocardial infarction than in those without, and the difference was significant (P<0.0001) in a linear regression analysis adjusted for age. When all the other variables were also included in a logistic regression model, serum calcium was a highly significant (P<0.0001) predictor of myocardial infarction in men, with an odds ratio of 1.2 per 0.1 mmol/L increase in serum calcium. In women, a nonsignificant trend was again seen. Because the free or ionized form of calcium is the physiologically important form and serum calcium was not corrected for serum albumin in our study, the results must be interpreted with caution. However, it appears likely that serum calcium is a predictor of cardiovascular disease in men.

Serum parathyroid hormone as a predictor of increase in systolic blood pressure in men.

Background In cross-sectional studies there appears to be a link between calcium metabolism and blood pressure, and most studies have found a positive association between serum parathyroid hormone (PTH) and hypertension. Objective To determine the prognostic value of serum PTH regarding a future increase in blood pressure. Design A prospective cohort study. Subjects A total of 1784 individuals who had measurements of PTH in serum samples from both the fourth (1994) and fifth (2001) Tromsø studies, who did not use blood pressure medication during the observation period, and had serum calcium less than 2.61 mmol/l, were included. Main outcome measure Delta blood pressure (blood pressure from 2001 minus blood pressure from 1994). Results The mean delta systolic blood pressure in the men and women during these 7 years was 5.8 and 8.1 mmHg, respectively. In a sex-specific linear regression model correcting for age, body mass index (BMI), and smoking status, serum PTH from 1994 was a significant predictor of delta systolic blood pressure in men (P < 0.01), but not in women. The difference in delta systolic blood pressure between those in the highest and those in the lowest PTH quartile was 3.5 mmHg. Similarly, delta serum PTH (serum PTH from 2001 minus serum PTH from 1994) was a significant predictor of delta systolic blood pressure in men (P < 0.05). Conclusions Although these findings do not prove a causal relationship between PTH and blood pressure, it adds to the growing number of indications that PTH is involved in the development of hypertension.

Relation Between Low Calcium Intake, Parathyroid Hormone, and Blood Pressure

In a population health survey in 1995, serum parathyroid hormone (PTH) was measured in 1113 subjects, aged 30 to 79 years, and was found to be elevated (>6.9 pmol/L) in 118 subjects. In 1998, this group and 131 subjects with normal PTH levels were invited for reexamination, and 82 and 90 subjects from each respective group attended the follow-up. At the follow-up, 72 subjects had elevated and 100 had normal serum PTH levels. Those with elevated serum PTH levels (8 subjects with hyperparathyroidism were excluded) had significantly lower serum calcium levels and intake of calcium than those with normal PTH (2.24+/-0.09 and 2.29+/-0.10 mmol/L [mean+/-SD] and 400.3+/-227.3 and 592.1+/-459.6 mg/d, respectively; P<0.01). Serum levels or intake of vitamin D did not differ between the 2 groups. Subjects with elevated PTH in both 1995 and 1998 had significantly lower bone mineral content and bone mineral density in the lumbar spine than did those with persistently normal PTH levels (P<0.05). In the females, but not in the males, the systolic and diastolic blood pressures were significantly higher in those with elevated serum PTH (158.0+/-27.5 versus 141.5+/-19.2 mm Hg and 90. 5+/-13.6 versus 82.6+/-8.6 mm Hg, respectively; P<0.01). This difference was even more pronounced when those with persistently elevated PTH were considered separately. In conclusion, reduced intake of calcium is frequently associated with high levels of serum PTH. This is associated with moderately reduced bone mineral content and bone mineral density in the lumbar spine. In women, high levels of serum PTH are also associated with markedly increased blood pressure.

Primary hyperparathyroidism detected in a health screening. The Trømsø study.

Serum calcium was measured in 12,339 men and 13,394 women ages 25 to 75. Primary hyperparathyroidism, defined as a combination of serum calcium and parathyroid hormone (PTH) levels within the extreme or upper normal range, was diagnosed in 17 men and 47 women. The prevalence in both sexes increased with age. When 42 subjects with asymptomatic primary hyperparathyroidism were followed for 3 years, no significant increase in serum calcium or PTH was seen. In a subgroup of 473 men and 517 women ages 50 to 75, serum PTH was measured along with serum calcium. Depending on the criteria used to define primary hyperparathyroidism, the prevalence in older women within this subgroup ranged from 3.6% to 13.9%. The study concluded that a high prevalence of primary hyperparathyroidism exists in older women, although the progression of the disease, judging by serum calcium and PTH measurements, appears to be very slow.

Neuropsychological dysfunction in systemic lupus erythematosus is not associated with changes in cerebral blood flow

Abstract Cognitive dysfunction is found in a considerable proportion of patients with systemic lupus erythematosus (SLE). SPECT provides an estimate of regional cerebral blood flow (rCBF) which has been claimed to be sensitive to detect brain involvement in SLE. It is, however, uncertain if these perfusion defects are related to cognitive dysfunction. In the present study we investigated whether cerebral dysfunction assessed by neuropsychological measures was associated with changes in rCBF. Fifty-two SLE patients were examined with a battery of neuropsychological tests and MRI of the brain. For each patient 99mTC-HMPAO-SPECT was performed with the visual cortex as reference, and a reduction in rCBF of > 15 % was considered abnormal. Regional CBF was performed with an automated computer program quantitatively estimating blood perfusion in 16 symmetrical sectors of the brain. Several sectors of the brain showed varying areas of reduced rCBF with the temporal lobes most frequently involved. There were generally no associations between cognitive level of functioning and reduced rCBF. MRI demonstrated cerebral infarcts in 9 (17 %) patients. In general rCBF was reduced in all sectors of the brain in patients with infarcts, although statistical significant difference in rCBF between patients with and without infarcts was only seen in the parietal lobe. Several neuropsychological functions were influenced by the presence of cerebral infarcts. There was no significant association between immunological measures and SPECT findings or neuropsychological measures. Neuropsychological dysfunction in SLE was associated with the presence of cerebral infarcts detected by MRI, but not by changes in rCBF. SPECT seems to add little if any information to that obtained by clinical examination, neuropsychological testing, and MRI. Since anticoagulation may prevent cerebral infarcts, such prophylactic intervention may be of importance in preventing cognitive deterioration.

The associations of endogenous testosterone and sex hormone-binding globulin with glycosylated hemoglobin levels, in community dwelling men. The Tromsø Study

OBJECTIVES Low levels of endogenous testosterone have been associated with increased risk of cardiovascular disease and atherosclerosis in men. Long-term hyperglycemia, as measured by glycosylated hemoglobin (HbA1c), is related to cardiovascular mortality, and HbA1c across its normal range is also positively related to coronary heart and cardiovascular disease mortality in men. We therefore undertook an analysis of the cross-sectional associations of total testosterone and SHBG levels with HbA1c levels, in a general population of 1419 men aged 25-84. METHODS Total testosterone, sex hormone-binding globulin (SHBG) and HbA1c were measured by immuno-assay. Partial correlation and multiple regression analyses were used to estimate the associations between total testosterone and SHBG with HbA1c. Analyses of variance and covariance were used to compare men with or without diabetes. RESULTS In age-adjusted partial correlation HbA1c was inversely associated with total testosterone (p<0.01) and SHBG (p<0.001). HbA1c was positively associated with body mass index (BMI) and waist circumference (WC) (p<0.001). In multiple regression analyses total testosterone, SHBG, age, number of cigarettes smoked, BMI and WC were independently associated with HbA1c levels. Men with a history of diabetes had lower levels of total testosterone in age-adjusted analyses (p<0.05) and lower levels of SHBG in both age- and WC-adjusted analyses (p<0.001 and p<0.01, respectively). CONCLUSION Lower levels of total testosterone and SHBG were associated with increased HbA1c levels and diabetes independent of concomitant variations in obesity and body fat distribution.

Determinants of serum calcium in men and women. The Tromsø Study.

The level of serum calcium appears to be associated with blood pressure and metabolic risk factors for cardiovascular disease. Determinants of serum calcium may therefore be of interest. In a health survey in Tromsø in 1994–1995, 27,159 subjects were examined. The survey included measurements of serum calcium and questionnaires on diet and lifestyle factors. In males mean serum calcium declined from 2.41 mmol/l for those in their 20s to 2.34 mmol/l for those in their 80s. In females mean serum calcium was stable at a level of 2.35 mmol/l before the menopause, and thereafter reached a plateau of 2.39 mmol/l. In both sexes serum calcium showed a positive association with body mass index (BMI) and coffee consumption that persisted after correcting for other variables in a multiple regression model (p < 0.05). Physical activity had no significant association with serum calcium. In females alcohol consumption was negatively, and cigarette smoking positively associated with serum calcium (p < 0.01). No significant effect on the serum calcium levels was found for the intake of calcium or vitamin D, except for males with a calcium intake below 200 mg/day. Some of the observed effects, like the variation with age, may partly be explained by alterations in levels of serum albumin to which approximately 40% of circulating calcium is bound and which was not adjusted for in this study, whereas that is hardly the case for the association with BMI and coffee consumption. However, none of these factors could affect the serum calcium level more than 0.02 mmol/l, and the biological significance of the observed associations questionable.