Early signatures of bleeding and mortality in patients on left ventricular assist device support: novel methods for personalized risk-stratification.

Background: Left ventricular assist devices (LVADs) provide support for patients with end-stage heart failure. The aims of this study were to determine whether baseline analysis and early trends in routine laboratory data, platelet activity, and thromboinflammatory biomarkers following LVAD implantation reveal trends that predict personalized risks of one-year gastrointestinal (GI) bleeding, stroke, pump thrombosis, drive-line infections and mortality in patients on LVAD support. Methods: We performed an observational study at the University of Kentucky with 61 participants who underwent first-time LVAD implantation. Blood was collected at baseline and post-op days 0, 1, 3 and 6 as well as clinical follow-up. Demographics, clinical characteristics, one-year adverse events and routine laboratory data were collected from electronic medical records. Platelet function and plasma biomarkers were profiled. Results: Evaluation of routine laboratory results revealed that sustained thrombocytopenia and increased mean platelet volume (MPV) were associated with development of GI bleeding and mortality. Platelet function at follow-up visit predicted one-year bleeding events. Thrombotic biomarker sCD40L strongly predicted one-year GI bleeding at baseline before implantation and within the first week following LVAD implant. Conclusions: Early trends in routine bloodwork and platelet function may serve as novel signatures of patients at risk to experience adverse events.

Association of orthostatic blood pressure response with incident heart failure: The Framingham Heart Study.

IMPORTANCE: Orthostatic hypotension (OH) and hypertension (OHT) are aberrant blood pressure (BP) regulation conditions associated with higher cardiovascular disease risk. The relations of OH and OHT with heart failure (HF) risk in the community are unclear and there remains a paucity of data on the relations with HF subtypes [HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF)]. OBJECTIVE: Relate OH and OHT with HF risk and its subtypes. DESIGN: Prospective observational cohort. SETTING: Community-based individuals in the Framingham Heart Study Original Cohort. PARTICIPANTS: 1,914 participants (mean age 72 years; 1159 women) attending examination cycle 17 (1981-1984) followed until December 31, 2017 for incident HF or death. EXPOSURES: OH or OHT, defined as a decrease or increase, respectively, of ≥20/10 mmHg in systolic/diastolic BP upon standing from supine position. OUTCOMES AND MEASURES: At baseline, 1,241 participants had a normal BP response (749 women), 274 had OH (181 women), and 399 had OHT (229 women). Using Cox proportional hazards regression models, we related OH and OHT to risk of HF, HFrEF, and HFpEF compared to the absence of OH and OHT (reference), adjusting for age, sex, body mass index, systolic and diastolic BP, hypertension treatment, smoking, diabetes, and total cholesterol/high-density lipoprotein. RESULTS: On follow-up (median 13 years) we observed 492 HF events (292 in women; 134 HFrEF, 116 HFpEF, 242 HF indeterminate EF). Compared to the referent, participants with OH [n = 84/274 (31%) HF events] had a higher HF risk (Hazards Ratio [HR] 1.47, 95% CI 1.13-1.91). Moreover, OH was associated with a higher HFrEF risk (HR 2.21, 95% CI 1.34-3.67). OHT was not associated with HF risk. CONCLUSIONS AND RELEVANCE: Orthostatic BP response may serve as an early marker of HF risk. Findings suggest shared pathophysiology of BP regulation and HF, including HFrEF.

Association of Estimated Cardiorespiratory Fitness in Midlife With Cardiometabolic Outcomes and Mortality.

Importance: The associations of estimated cardiorespiratory fitness (eCRF) during midlife with subclinical atherosclerosis, arterial stiffness, incident cardiometabolic disease, and mortality are not well understood. Objective: To examine associations of midlife eCRF with subclinical atherosclerosis, arterial stiffness, incident cardiometabolic disease, and mortality. Design, Setting, and Participants: This cohort study included 2962 participants in the Framingham Study Second Generation (conducted between 1979 and 2001). Data were analyzed from January 2020 to June 2020. Exposures: eCRF was calculated using sex-specific algorithms (including age, body mass index, waist circumference, physical activity, resting heart rate, and smoking) and was categorized as: (1) tertiles of standardized eCRF at examination cycle 7 (1998 to 2001); (2) tertiles of standardized average eCRF between examination cycles 2 and 7 (1979 to 2001); and (3) eCRF trajectories between examination cycles 2 and 7, with the lowest tertile or trajectory (ie, low eCRF) as referent group. Main Outcomes and Measures: Subclinical atherosclerosis (carotid intima-media thickness [CIMT], coronary artery calcium [CAC] score); arterial stiffness (carotid-femoral pulse wave velocity [-1000/CFPWV]); incident hypertension, diabetes, chronic kidney disease (CKD), cardiovascular disease (CVD), and mortality after examination cycle 7. Results: A total of 2962 participants were included in this cohort study (mean [SD] age, 61.5 [9.2] years; 1562 [52.7%] women). The number of events or participants at risk after examination cycle 7 (at a mean follow-up of 15 years) was 728 of 1506 for hypertension, 214 of 2268 for diabetes, 439 of 2343 for CKD, 500 of 2608 for CVD, and 770 of 2962 for mortality. Compared with the low eCRF reference value, high single examination eCRF was associated with lower CFPWV (ß [SE], -11.13 [1.33] ms/m) and CIMT (ß [SE], -0.12 [0.05] mm), and lower risk of hypertension (hazard ratio [HR], 0.63; 95% CI, 0.46-0.85), diabetes (HR, 0.38; 95% CI, 0.23-0.62), and CVD (HR, 0.71; 95% CI, 0.53-0.95), although it was not associated with CKD or mortality. Similarly, compared with the low eCRF reference, high eCRF trajectories and mean eCRF were associated with lower CFPWV (ß [SE], -11.85 [1.89] ms/m and -10.36 [1.54] ms/m), CIMT (ß [SE], -0.19 [0.06] mm and -0.15 [0.05] mm), CAC scores (ß [SE], -0.67 [0.25] AU and -0.63 [0.20] AU), and lower risk of hypertension (HR, 0.54; 95% CI, 0.34-0.87 and HR, 0.48; 95% CI, 0.34-0.68), diabetes (HR, 0.27; 95% CI, 0.15-0.48 and HR, 0.31; 95% CI, 0.18-0.54), CKD (HR, 0.63; 95% CI, 0.40-0.97 and HR, 0.64; 95% CI, 0.44-0.94), and CVD (HR, 0.46; 95% CI, 0.31-0.68 and HR, 0.43; 95% CI, 0.30-0.60). Compared with the reference value, a high eCRF trajectory was associated with lower risk of mortality (HR, 0.69; 95% CI, 0.50-0.95). Conclusions and Relevance: In this cohort study, higher midlife eCRF was associated with lower burdens of subclinical atherosclerosis and vascular stiffness, and with a lower risk of hypertension, diabetes, chronic kidney disease, cardiovascular disease, and mortality. These findings suggest that midlife eCRF may serve as a prognostic marker for subclinical atherosclerosis, arterial stiffness, cardiometabolic health, and mortality in later life.

Hypertension update, JNC8 and beyond.

Hypertension is the most preventable major risk factor for cardiovascular morbidity and mortality. The etiology of elevated blood pressure is a complex process involving the interaction of genetics, demographics, comorbid disorders, and environmental influences. Effective hypertensive therapy has been shown to reduce cardiovascular morbidity and mortality. JNC reports have served as a valuable source of guidelines, and JNC 8 is the most recently updated guideline for the prevention, diagnosis, and treatment of hypertension. It includes modification of JNC 7 regarding the threshold for therapy, therapeutic goals, and medications or combinations of medications that differ in benefits for certain patient populations. However, JNC 8 generated a significant degree of controversy. This review will evaluate JNC 7 versus JNC 8 guidelines and discuss the most controversial aspects of JNC 8 through a therapeutic perspective. This review will also discuss the most recently available evidence that has an impact on the JNC 8 recommendations. Despite the nuance of clinical guidelines, blood pressure control rates remains suboptimal. We will explore potential reasons and solutions for this dilemma including pharmacogenomics, novel risk-stratification strategies, lifestyle interventions, and integrative care.