Project description:Recent publications have stated that the blood pressure (BP) measurement technique used in SPRINT (Systolic Blood Pressure Intervention Trial) was unattended. However, the SPRINT protocol does not address the issue of attendance. A survey was conducted immediately after SPRINT closeout visits were completed to inquire whether BP measurements were usually attended or unattended by staff. There were 4082 participants at 38 sites that measured BP after leaving the participant alone the entire time (always alone), 2247 at 25 sites that had personnel in the room the entire time (never alone), 1746 at 19 sites that left the participant alone only during the rest period (alone for rest), and 570 at 6 sites that left the participant alone only during the BP readings (alone for BP measurement). Similar systolic and diastolic BPs within randomized groups were noted during follow-up at the majority of visits in all 4 measurement categories. In the always alone and never alone categories, the intensive group had a similarly reduced risk for the primary outcome compared with the standard group (hazard ratio, 0.62; 95% confidence interval, 0.51-0.76 and hazard ratio, 0.64; 95% confidence interval, 0.46-0.91, respectively; pairwise interaction P value, 0.88); risk was not significantly reduced for the intensive group in the smaller alone-for-rest and the alone-for-BP-measurement categories. Similar BP levels and cardiovascular disease risk reduction were observed in the intensive group in SPRINT participants whether the measurement technique used was primarily attended or unattended.Clinical trial registrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT01206062.
Project description:Adriatic islanders have a high prevalence of metabolic syndrome that is not fully explained by previous behavioral, dietary, and genetic studies. Some DNA methylation remains stable and may be established in early life, whereas others are dynamic and may vary over time in response to different conditions. The objective of the present study was to identify stable and dynamic DNA methylation loci associated with cardiometabolic traits among the populations from the island of Hvar, the largest island in the eastern Adriatic coast. An epigenome-wide association study (EWAS) was conducted using peripheral blood that was longitudinally collected at two time points, 10 years apart. DNA methylation was analyzed via Infinium MethylationEPIC BeadArray. Stable and dynamic loci were identified using linear mixed models. A total of 43,041 loci were classified as stable, while 45,769 loci were classified as dynamic. Associations between various cardiometabolic traits and stable and dynamic methylation loci were respectively assessed using linear mixed effects models adjusted for age, sex, and smoking status. After adjustment for false-discovery rate, 24 CpG loci were significantly associated with systolic blood pressure (Q < 0.1), of which 22 were stable loci and 2 were dynamic loci; while 12/22 (55%) of the systolic blood-pressure-associated stable loci resided in a gene promoter. Additionally, there was one stable locus associated with serum calcium and one with C-reactive protein. The results suggest that multiple genes involved in the determination of systolic blood pressure may be regulated via epigenetic programming established in early life.
Project description:BackgroundBrain perivascular spaces (PVS) are part of the glymphatic system and facilitate clearance of metabolic byproducts. Since enlarged PVS are associated with vascular health, we tested whether intensive systolic blood pressure (SBP) treatment affects PVS structure.MethodsThis is a secondary analysis of the Systolic PRessure INtervention Trial (SPRINT) MRI Substudy: a randomized trial of intensive SBP treatment to goal < 120 mm Hg vs < 140 mm Hg. Participants had increased cardiovascular risk, pre-treatment SBP 130-180, and no clinical stroke, dementia, or diabetes. Brain MRIs acquired at baseline and follow-up were used to automatically segment PVS in the supratentorial white matter and basal ganglia using a Frangi filtering method. PVS volumes were quantified as a fraction of the total tissue volume. The effects of SBP treatment group and major antihypertensive classes on PVS volume fraction were separately tested using linear mixed-effects models while covarying for MRI site, age, sex, Black race, baseline SBP, history of cardiovascular disease (CVD), chronic kidney disease, and white matter hyperintensities (WMH).ResultsFor 610 participants with sufficient quality MRI at baseline (mean age 67 ± 8, 40 % female, 32 % Black), greater PVS volume fraction was associated with older age, male sex, non-Black race, concurrent CVD, WMH, and brain atrophy. For 381 participants with MRI at baseline and at follow-up (median ± IQR = 3.9 ± 0.4 years), intensive treatment was associated with decreased PVS volume fraction relative to standard treatment (interaction coefficient: -0.029 [-0.055 to -0.0029] p = 0.029). Reduced PVS volume fraction was also associated with exposure to calcium channel blockers (CCB).ConclusionsPVS enlargement was partially reversed in the intensive SBP treatment group. The association with CCB use suggests that improved vascular compliance may be partly responsible. Improved vascular health may facilitate glymphatic clearance. Clincaltrials.gov: NCT01206062.
Project description:Cardiovascular morbidity and mortality was reduced by 25% when blood pressure (BP) was targeted to 120 mm Hg systolic compared with 140 mm Hg systolic in Systolic Blood Pressure Intervention Trial (SPRINT); however, BP was measured using a research technique. SPRINT specified 5 minutes of seated rest in a quiet room followed by 3 oscillometric measurements without an observer in the room. The relationship of this research-grade methodology to routine BP measurements is not known. Among 275 people with chronic kidney disease who had BP <140/90 mm Hg when they came to the clinic, we measured BP as in SPRINT and recorded BP on the same day without specification of seated rest. Compared with routine measurement, the research-grade systolic BP was 12.7 mm Hg lower with wide limits of agreement (-46.1 to 20.7 mm Hg). Research grade systolic BP was 7.9 mm Hg lower than daytime ambulatory systolic BP and had wide agreement limits (-33.2 to 17.4 mm Hg). Whereas the routine, research-grade, and daytime ambulatory systolic BP were all related to echocardiographic left ventricular hypertrophy, the strength of the relationship between research-grade and daytime ambulatory systolic BP to left ventricular hypertrophy was similar and stronger than the strength of the relationship between routine systolic BP and left ventricular hypertrophy. Taken together, these results suggest that translation of the SPRINT results will require measurement of BP as performed in that trial. Instead of an algebraic manipulation of routine clinic measurements, the SPRINT methodology of BP measurement would be needed at minimum if implementation of the SPRINT results were to be deployed in the population at large.
Project description:ObjectiveTo explore the proportion and characteristic of Chinese adults meeting The Systolic Blood Pressure Intervention Trial (SPRINT) eligibility criteria and assess its generalizability.MethodOur study was based on a cross-sectional, population-based survey with a sample of 26,093 participants aged over 20 years. The SPRINT eligibility criteria were age ≥ 50 years, elevated SBP of 130 to 180 mmHg depending on the number of antihypertensive medication classes being taken, and increased cardiovascular disease (CVD) but without diabetes, history of stroke and estimated glomerular filtration rate < 20 ml/min/1.73 m2, or receiving dialysis.ResultsOverall, we estimated that 4,036 (15.5%) participants would meet the SPRINT eligibility criteria. They were generally older, likely to be female, lower educational level, tended to be more overweight, and had higher Framingham risk score compared with overall population or subjects aged ≥ 50 years. Of participants eligible for SPRINT, most (56.2%) of them were not treated for hypertension, and 542 (13.4%) were not previously considered to have hypertension or need for antihypertension therapy. Among the 11,637 adults with hypertension, 3,494 (30.0%) would potentially benefit from treatment intensification. The most common antihypertensive medication class being taken was diuretic agents.ConclusionA substantial percentage of Chinese subjects meet the SPRINT eligibility criteria. Further studies are needed to assess the cost-effectiveness from treatment intensification in Chinese setting.
Project description:To investigate the optimal blood pressure (BP) in patients with coronary artery disease (CAD), we conducted subgroup analysis using SPRINT data. The study sample included 1206 participants with CAD (of whom 692 underwent coronary revascularization) and 8127 participants without CAD. Participants were randomized into two groups (systolic BP target of 140 mm Hg vs. 120 mm Hg). The primary outcome was a composite of cardiovascular events. After a median follow-up of 3.9 years, the hazard ratios (HRs) for the primary outcome were 0.65 (95% confidence interval (CI) 0.53-0.79) and 1.05 (95% CI 0.76-1.46) among those in the non-CAD and CAD subgroups, respectively (P value for interaction 0.02). Intensive BP treatment was a protective factor for all-cause death (HR 0.60, 95% CI 0.37-0.96) in the CAD subgroup, compared with standard BP treatment. The HRs (95% CI) for stroke were 3.57 (1.17-10.85) and 1.03 (0.29-3.62) among those in the coronary revascularization and non-revascularization subgroups, respectively (P value for interaction 0.13). For safety events, intensive BP treatment increased the risk of hypotension (HR 2.00, 95% CI 1.06-3.79) and electrolyte abnormalities (HR 2.38, 95% CI 1.25-4.56) in the CAD subgroup, while the risk of serious adverse events did not increase (HR 1.03, 95% CI 0.88-1.20). These results suggest that positive benefits from intensive BP treatment might be attenuated in patients with CAD who are under better secondary prevention. The risk of stroke might increase at the systolic BP target of 120 mm Hg in case of coronary revascularization, although the confidence interval was wide.