OBJECTIVES To determine whether plasma klotho, a recently discovered hormone that has been implicated in atherosclerosis, is related to prevalent cardiovascular disease in adults. DESIGN Cross-sectional. SETTING Population-based sample of adults residing in Tuscany, Italy. PARTICIPANTS One thousand and twenty-three men and women, aged 24–102, participating in the Invecchiare in Chianti (InCHIANTI) study. MEASUREMENTS Anthropometric measures, plasma klotho, fasting plasma total, high-density lipoprotein (HDL) cholesterol, triglycerides, glucose, creatinine, C-reactive protein. Clinical measures: medical assessment, diabetes mellitus, hypertension, coronary heart disease, heart failure, stroke, peripheral artery disease, cancer, chronic kidney disease. Logistic regression models were used to examine the relationship between plasma klotho and prevalent cardiovascular disease. RESULTS Of 1023 participants, 259 (25.3%) had cardiovascular disease. Median (25th, 75th percentile) plasma klotho concentrations were 676 (530, 819) pg/mL. Plasma klotho was correlated with age (r = −0.14, P <0.0001), HDL cholesterol (r = 0.11, P = 0.0004), C-reactive protein (r = −0.10, P = 0.0008), but not systolic blood pressure, fasting plasma glucose, or renal function. Plasma klotho age-adjusted geometric means (95% Confidence Interval [C.I.]) were 626 (601, 658) in participants with cardiovascular disease and 671 (652, 692) pg/mL in those without cardiovascular disease (P = 0.0001). Adjusting for traditional cardiovascular risk factors (age, sex, smoking, total cholesterol, HDL cholesterol, systolic blood pressure, and diabetes), log plasma klotho was associated with prevalent cardiovascular disease (Odds Ratio per 1 standard deviation increase = 0.85, 95% C.I. 0.72, 0.99). CONCLUSION In community-dwelling adults, higher plasma klotho concentrations are independently associated with a lower likelihood of having cardiovascular disease.

In older community-dwelling adults, plasma klotho is an independent predictor of all-cause mortality. Further studies are needed to elucidate the potential biological mechanisms by which circulating klotho could affect longevity in humans.

Background/Objectives Advanced glycation end products (AGEs) are implicated in the pathogenesis of atherosclerosis, diabetes, and kidney disease. The objective was to describe dietary intake, the dominant source of exposure to AGEs, with carboxymethyl-lysine (CML), a major AGE, in serum and urine, respectively. Subjects/Methods Serum and urinary CML were measured in 261 adults, aged 21–69 years, and compared with diet as assessed by six separate 24-hour dietary recalls. Results Median (25th, 75th percentile) serum and urinary CML concentrations were 686 (598, 803 μg/L) and 1023 (812, 1238) μg/gm creatinine. There was no correlation between serum and urinary CML (r = −0.02, P = 0.78). Serum CML was positively correlated with intake of soy, fruit juice, cold breakfast cereal, non-fat milk, whole grains, fruit, non-starchy vegetables, and legumes, and negatively correlated with intake of red meat. Intake of fast food was not significantly correlated with serum CML. Urinary CML was positively correlated with intake of starchy vegetables, whole grains, sweets, nuts/seeds, and chicken, and negatively correlated with intake of fast foods. Intake of AGE-rich foods such as fried chicken, French fries, bacon/sausage, and crispy snacks were not significantly correlated with serum or urinary CML, except for a significant negative correlation between fried chicken and serum CML. Conclusions These findings suggest that the high consumption of foods considered high in CML is not a major determinant of either serum or urinary CML. Further work is needed to understand the relationship of AGEs in blood and urine with the metabolism of dietary AGEs.