Orthostatic Hypertension and Hypotension and Outcomes in CKD: The CRIC (Chronic Renal Insufficiency Cohort) Study.

RATIONALE & OBJECTIVE: There are limited data about the prevalence and prognostic significance of orthostatic hypo- and hypertension in patients with chronic kidney disease. The objective of this study is to determine the prevalence of orthostatic hypo- and hypertension in a cohort of patients with chronic kidney disease and examine their association with clinical outcomes. STUDY DESIGN: Prospective cohort study: Chronic Renal Insufficiency Cohort (CRIC) Study. SETTING & POPULATION: 7 clinical centers, participants with chronic kidney disease. EXPOSURES: Orthostatic hypotension (decline in systolic blood pressure [BP] > 20 mm Hg) and orthostatic hypertension (increase in systolic BP > 20 mm Hg) from seated to standing position. OUTCOMES: Cardiovascular and kidney outcomes and mortality. ANALYTICAL APPROACH: Logistic regression was used to determine factors associated with orthostatic hypo- and hypertension; Cox regression was used to examine associations with clinical outcomes. RESULTS: Mean age of study population (n = 3,873) was 58.1 ± 11.0 years. There was a wide distribution of change in systolic BP from seated to standing (from -73.3 to +60.0 mm Hg); 180 participants (4.6%) had orthostatic hypotension and 81 (2.1%) had orthostatic hypertension. Diabetes, reduced body mass index, and ß-blocker use were independently associated with orthostatic hypotension. Black race and higher body mass index were independently associated with orthostatic hypertension. After a median follow-up of 7.9 years, orthostatic hypotension was independently associated with high risk for cardiovascular (HR, 1.12; 95% CI, 1.03-1.21) but not kidney outcomes or mortality. Orthostatic hypertension was independently associated with high risk for kidney (HR, 1.51; 96% CI, 1.14-1.97) but not cardiovascular outcomes or mortality. LIMITATIONS: Orthostatic change in BP was ascertained at a single visit. CONCLUSIONS: Orthostatic hypotension was independently associated with higher risk for cardiovascular outcomes, whereas orthostatic hypertension was associated with higher risk for kidney outcomes. These findings highlight the importance of orthostatic BP measurement in practice and the need for future investigation to understand the mechanisms and potential interventions to minimize the risk associated with orthostatic changes in BP.

BBSome ablation in SF1 neurons causes obesity without comorbidities.

OBJECTIVES: The hypothalamic ventromedial nucleus (VMH) plays a major role in metabolic control, but the molecular mechanisms involved remain poorly defined. We analyzed the relevance of the BBSome, a protein complex composed of 8 Bardet-Biedl syndrome (BBS) proteins including BBS1, in VMH steroidogenic factor 1 (SF1) neurons for the control of energy homeostasis and related physiological processes. METHODS: We generated mice bearing selective BBSome disruption, through Bbs1 gene deletion, in SF1 neurons (SF1Cre/Bbs1fl/fl). We analyzed the consequence on body weight, glucose homeostasis, and cardiovascular autonomic function of BBSome loss in SF1 neurons. RESULTS: SF1Cre/Bbs1fl/fl mice had increased body weight and adiposity under normal chow conditions. Food intake, energy absorption, and digestive efficiency were not altered by Bbs1 gene deletion in SF1 neurons. SF1Cre/Bbs1fl/fl mice exhibited lower energy expenditure, particularly during the dark cycle. Consistent with this finding, SF1Cre/Bbs1fl/fl mice displayed reduced sympathetic nerve traffic and expression of markers of thermogenesis in brown adipose tissue. SF1Cre/Bbs1fl/fl mice also had lower sympathetic nerve activity to subcutaneous white adipose tissue that was associated with a protein expression profile that promotes lipid accumulation. Notably, despite obesity and hyperinsulinemia, SF1Cre/Bbs1fl/fl mice did not exhibit significant changes in glucose metabolism, insulin sensitivity, blood pressure, and baroreflex sensitivity. CONCLUSIONS: Our findings demonstrate that the SF1 neuron BBSome is necessary for the regulation of energy homeostasis through modulation of the activity of the sympathetic nervous system and that the SF1 neuron BBSome is required for the development of obesity-related comorbidities.

Midterm outcomes in patients with upper extremity deep vein thrombosis.

BACKGROUND: Outcomes and the necessity for anticoagulation in patients with upper extremity deep vein thrombosis (UE DVT) are unclear. The purpose of this study was to determine the incidence of UE DVT, the outcomes of patients stratified by anticoagulation treatment, and which factors were significantly associated with mortality. METHODS: This study was a single-center, retrospective review of all patients undergoing UE venous duplex imaging in 2016. Information on patients' demographics, relevant comorbidities, use of anticoagulation at the time of diagnosis, characteristics of the UE DVT, treatment regimen(s), and outcomes was collected. Data were analyzed using descriptive and univariate statistics; multivariate logistic regression and Cox proportional hazard models were used to identify which of the aforementioned covariates are significantly associated with mortality rates at 30 days and 6 months, respectively, at a 95% confidence level. RESULTS: Of the 911 patients undergoing UE venous duplex imaging, 182 (20.0%) were positive for UE DVT. Within the first 30 days, 30 patients (16.5%) died, 13 (7.1%) had pulmonary emboli, 42 (23.1%) had either pulmonary emboli or died, and 3 (1.6%) had ischemic strokes. Within the first 6 months, 50 patients (27.5%) died. The mortality rate at 30 days was found to be significantly increased in patients who were older (odds ratio [OR], 1.06; P < .01), had high-risk contraindications to anticoagulation (OR, 5.14; P < .01), were on dialysis (OR, 3.03; P = .04), had centrally located UE DVTs (OR, 2.72; P < .05), and had a stroke (OR, 20.34; P = .03). Mortality was significantly decreased in patients who were treated with anticoagulation (OR, 0.16; P < .05). At 6 months, however, age (hazard ratio [HR], 1.05; P < .001), male sex (HR, 2.16; P = .02), dialysis (HR, 2.90; P = .01), high-risk contraindications to anticoagulation (HR, 2.67; P = .02), UE DVTs in both central and peripheral veins (HR, 4.55; P = .03), and ischemic stroke in the first 30 days (HR, 71.63; P < .001) were associated with significant increases in mortality. CONCLUSIONS: These data suggest that mortality rates among patients with UE DVT are relatively high and that treatment with anticoagulation is associated with a decrease in mortality at 30 days. Mortality was also associated with multiple comorbid conditions and demographics and not necessarily venous thromboembolism.