Background Conventional coronary artery disease risk factors might potentially explain at least 90% of the attributable risk of coronary artery disease. To better understand the association between the pre-industrial lifestyle and low prevalence of coronary artery disease risk factors, we examined the Tsimane, a Bolivian population living a subsistence lifestyle of hunting, gathering, fishing, and farming with few cardiovascular risk factors, but high infectious inflammatory burden. Methods We did a cross-sectional cohort study including all individuals who self-identified as Tsimane and who were aged 40 years or older. Coronary atherosclerosis was assessed by coronary artery calcium (CAC) scoring done with non-contrast CT in Tsimane adults. We assessed the difference between the Tsimane and 6814 participants from the Multi-Ethnic Study of Atherosclerosis (MESA). CAC scores higher than 100 were considered representative of significant atherosclerotic disease. Tsimane blood lipid and inflammatory biomarkers were obtained at the time of scanning, and in some patients, longitudinally. Findings Between July 2, 2014, and Sept 10, 2015, 705 individuals, who had data available for analysis, were included in this study. 596 (85%) of 705 Tsimane had no CAC, 89 (13%) had CAC scores of 1–100, and 20 (3%) had CAC scores higher than 100. For individuals older than age 75 years, 31 (65%) Tsimane presented with a CAC score of 0, and only four (8%) had CAC scores of 100 or more, a five-fold lower prevalence than industrialised populations (p≤0-0001 for all age categories of MESA). Mean LDL and HDL cholesterol concentrations were 2.35 mmol/L (91 mg/dL) and 1.0 mmol/L (39.5 mg/dL), respectively; obesity, hypertension, high blood sugar, and regular cigarette smoking were rare. High- sensitivity C-reactive protein was elevated beyond the clinical cutoff of 3.0 mg/dL in 360 (51%) Tsimane participants. Interpretation Despite a high infectious inflammatory burden, the Tsimane, a forager-horticulturalist population of the Bolivian Amazon with few coronary artery disease risk factors, have the lowest reported levels of coronary artery disease of any population recorded to date. These findings suggest that coronary atherosclerosis can be avoided in most people by achieving a lifetime with very low LDL, low blood pressure, low glucose, normal body-mass index, no smoking, and plenty of physical activity. The relative contributions of each are still to be determined. Funding National Institute on Aging, National Institutes of Health; St Luke's Hospital of Kansas City; and Paleocardiology Foundation.

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Conclusion:Atherosclerosis was common in four preindustrial popu-

Several symptoms and signs of hyperthyroidism are frequently shared by patients receiving L-T4 suppressive therapy. The aim of this study was to evaluate whether a beta-adrenergic blocking drug could reduce the severity of these symptoms and signs in these patients, as previously reported in patients with hyperthyroidism. Eleven patients (mean age, 42 +/- 11 yr; 10 females and one male) affected with differentiated thyroid carcinoma or nontoxic goiter were selected from a more numerous group of patients receiving suppressive therapy based on the presence of palpitations, increased heart rate, left ventricular systolic function, and other symptoms mimicking exaggerated beta-adrenergic activity. In these patients the cardioselective beta-blocking drug bisoprolol was added to the L-T4 suppressive therapy at a dose of 2.5-5 mg/day. Blood samples were collected for the determination of thyroid hormones and TSH concentration during L-T4 therapy and after 3 and 6 months of associated L-T4 plus bisoprolol therapy. Cardiac function was assessed by clinical evaluation, standard and Holter electrocardiogram, as well as one- and two-dimensional echocardiography. Furthermore, we applied the symptom-rating scale previously used by Klein et al. in hyperthyroid patients to assess the quality of life in our group of patients. Our findings show that the addition of bisoprolol to L-T4 suppressive therapy produces a normalization of heart rate, which was significantly increased during TSH suppressive therapy, and the disappearance of atrial arrhythmias with considerable reduction of palpitations. Furthermore, bisoprolol produced an effective improvement in measures of the hyperthyroid symptom scale, with significant reduction of the mean score. The echocardiographic data showed an increased left ventricular mass index with significantly enhanced systolic function at the basal evaluation. After 6 months of combined L-T4 plus bisoprolol therapy, left ventricular mass index normalized, and the indices of left ventricular systolic function were reduced, with a tendency to normalize. Further studies conducted on a larger series of patients are required to verify the long term implications of cardiac parameter variations on cardiovascular morbidity and mortality. Our results, however, show that the addition of bisoprolol to L-T4 suppressive therapy improves the quality of life in those patients with clinical features of enhanced adrenergic activity.