Pulse Wave Velocity Is Associated with Increased Plasma oxLDL in Ageing but Not with FGF21 and Habitual Exercise.

Fibroblast growth factor 21 (FGF21) and adiponectin increase the expression of genes involved in antioxidant pathways, but their roles in mediating oxidative stress and arterial stiffness with ageing and habitual exercise remain unknown. We explored the role of the FGF21-adiponectin axis in mediating oxidative stress and arterial stiffness with ageing and habitual exercise. Eighty age- and sex-matched healthy individuals were assigned to younger sedentary or active (18-36 years old, n = 20 each) and older sedentary or active (45-80 years old, n = 20 each) groups. Arterial stiffness was measured indirectly using pulse wave velocity (PWV). Fasted plasma concentrations of FGF21, adiponectin and oxidized low-density lipoprotein (oxLDL) were measured. PWV was 0.2-fold higher and oxLDL concentration was 25.6% higher (both p < 0.001) in older than younger adults, despite no difference in FGF21 concentration (p = 0.097) between age groups. PWV (p = 0.09) and oxLDL concentration (p = 0.275) did not differ between activity groups but FGF21 concentration was 9% lower in active than sedentary individuals (p = 0.011). Adiponectin concentration did not differ by age (p = 0.642) or exercise habits (p = 0.821). In conclusion, age, but not habitual exercise, was associated with higher oxidative stress and arterial stiffness. FGF21 and adiponectin did not differ between younger and older adults, meaning that it is unlikely that they mediate oxidative stress and arterial stiffness in healthy adults.

Fibroblast Growth Factor 21 Mediates the Associations between Exercise, Aging, and Glucose Regulation.

INTRODUCTION: Aging increases the prevalence of glucose intolerance, but exercise improves glucose homeostasis. The fibroblast growth factor 21 (FGF21)-adiponectin axis helps regulate glucose metabolism. However, the role of FGF21 in mediating glucose metabolism with aging and exercise remains unknown. PURPOSE: This study examined whether FGF21 responses to a glucose challenge are associated with habitual exercise, aging and glucose regulation. METHODS: Eighty age- and sex-matched healthy individuals were assigned to young sedentary and active (≤36 yr, n = 20 each group) and older sedentary and active (≥45 yr, n = 20 each group) groups. Fasted and postprandial blood glucose concentration and plasma concentration of insulin, FGF21, and adiponectin were determined during an oral glucose tolerance test (OGTT). RESULTS: During the OGTT, glucose concentrations were 9% higher (P = 0.008) and FGF21 concentrations were 58% higher (P = 0.014) in the older than the younger group, independent of activity status. Active participants had 40% lower insulin concentration and 53% lower FGF21 concentration than sedentary participants, independent of age (all P < 0.001). Adiponectin concentration during the OGTT did not differ by age (P = 0.448) or activity status (P = 0.611). Within the younger group, postprandial glucose, insulin and FGF21 concentrations during the OGTT were lower in active than in sedentary participants. In the older group, only postprandial insulin and FGF21 concentrations were lower in active participants. CONCLUSIONS: FGF21, but not adiponectin, response during the OGTT is higher in older than younger adults and lower in active than sedentary individuals. Exercise-associated reduction in OGTT glucose concentrations was observed in younger but not older adults.

Myocardial contractile dysfunction associated with increased 3-month and 1-year mortality in hospitalized patients with heart failure and preserved ejection fraction.

BACKGROUND: There is a clinical need for a contractility index that reflects myocardial contractile dysfunction even when ejection fraction (EF) is preserved. We used novel relative load-independent global and regional contractility indices to compare left ventricular (LV) contractile function in three groups: heart failure (HF) with preserved ejection fraction (HFPEF), HF with reduced ejection fraction (HFREF) and normal subjects. Also, we determined the associations of these parameters with 3-month and 1-year mortality in HFPEF patients. METHODS: 199 HFPEF patients [median age (IQR): 75 (67-80) years] and 327 HFREF patients [69 (59-76) years] were recruited following hospitalization for HF; 22 normal control subjects [65 (54-71) years] were recruited for comparison. All patients underwent standard two-dimensional Doppler and tissue Doppler echocardiography to characterize LV dimension, structure, global and regional contractile function. RESULTS: The median (IQR) global LV contractility index, dσ*/dtmax was 4.30s(-1) (3.51-4.57s(-1)) in normal subjects but reduced in HFPEF [2.57 (2.08-3.64)] and HFREF patients [1.77 (1.34-2.30)]. Similarly, median (IQR) regional LV contractility index was 99% (88-104%) in normal subjects and reduced in HFPEF [81% (66-96%)] and HFREF [56% (41-71%)] patients. Multi-variable logistic regression analysis on HFPEF identified sc-mFS <76% as the most consistent predictor of both 3-month (OR=7.15, p<0.05) and 1-year (OR=2.57, p<0.05) mortality after adjusting for medical conditions and other echocardiographic measurements. CONCLUSION: Patients with HFPEF exhibited decreased LV global and regional contractility. This population-based study demonstrated that depressed regional contractility index was associated with higher 3-month and 1-year mortality in HFPEF patients.

Bromocriptine use and the risk of valvular heart disease.

It has been reported that patients on pergolide and carbergoline have an increased risk of developing valvular heart disease. It is uncertain if bromocriptine, an ergot-derived dopamine agonist (DA) with partial 5-HT(2B) activity, is associated with a similar risk. We assessed the frequency of valvular heart disease in Parkinson's disease (PD) patients on bromocriptine compared to pergolide and a control group of PD patients who had not been treated on any DA. Seventy-two PD patients on bromocriptine, 21 patients on pergolide, and 47 control PD patients were recruited. Transthoracic echocardiographic studies were performed and reviewed by a blinded cardiologist. The risk for the bromocriptine group to develop any abnormal valvular regurgitation was 3.32 (adjusted OR, 95% CI: 1.11-9.92, P = 0.03) compared to controls, whereas the risk for the pergolide group was 3.66 (adjusted OR, 95% CI: 1.22-10.97, P = 0.02). When cumulative dose of bromocriptine was analyzed by quartiles, patients with a greater exposure to bromocriptine had significantly higher risk of developing both mild and moderate-severe regurgitations (P for trend, 0.005 and 0.019, respectively). This study demonstrated that bromocriptine use was associated with an increased risk of developing valvular heart disease, which occurred in a cumulative dose-dependent manner.