Blood Pressure-lowering Medication Research Articles

Association of Blood Pressure With Cause-Specific Mortality in Mexican Adults

Elevated blood pressure is a major cause of premature death, but there is little direct evidence demonstrating this association in studies of Hispanic populations. To assess the association between blood pressure and cause-specific mortality in a large cohort of Mexican adults with a high prevalence of uncontrolled diabetes. A total of 159 755 adults aged 35 years or older from 2 districts in Mexico City were recruited to this cohort study between April 1998 and September 2004 and followed up until January 2018. The present analyses focused on 133 613 participants who were aged 35 to 74 years and had no history of chronic disease besides diabetes. Blood pressure. Cox regression, adjusted for confounders, yielded mortality rate ratios (RRs) for deaths of participants occurring between ages 35 and 74 years. Of the 133 613 participants (43 263 [32.4%] men; mean [SD] age, 50 [11] years), 16 911 (12.7%) had self-reported previously diagnosed diabetes (including 8435 [6.3%] with uncontrolled diabetes, defined as hemoglobin A1c ≥9%) and 6548 (4.9%) had undiagnosed diabetes. Systolic blood pressure (SBP) was associated with vascular mortality between ages 35 to 74 years, with each 20 mm Hg lower usual SBP associated with 35% lower vascular mortality (RR, 0.65; 95% CI, 0.61-0.68), including 48% lower stroke mortality (RR, 0.52; 95% CI, 0.47-0.59) and 32% lower ischemic heart disease mortality (RR, 0.68; 95% CI, 0.63-0.74). These RRs were broadly similar in those with and without diabetes. Compared with those without diabetes and SBP less than 135 mm Hg at recruitment, the vascular mortality RR was 2.8 (95% CI, 2.4-3.3) for those without diabetes and SBP of 155 mm Hg or greater, 4.7 (95% CI, 4.1-5.4) for those with uncontrolled diabetes and SBP less than 135 mm Hg, and 8.9 (95% CI, 7.2-11.1) for those with uncontrolled diabetes and SBP of 155 mm Hg or greater. Lower SBP was also associated with decreased kidney-related mortality (RR per 20 mm Hg lower usual SBP, 0.69; 95% CI, 0.64-0.74), decreased mortality from infection (RR, 0.81; 95% CI, 0.71-0.91), and decreased mortality from hepatobiliary disease (RR, 0.87; 95% CI, 0.78-0.98), but not decreased neoplastic or respiratory mortality. SBP was more informative for vascular mortality than other blood pressure measures (eg, compared with SBP, diastolic blood pressure was only two-thirds as informative). Blood pressure was most strongly associated with vascular and kidney-related mortality in this Mexican population, with particularly high absolute excess mortality rates among individuals with diabetes. The findings reinforce the need for more widespread use of blood pressure-lowering medication in Mexico, particularly among those with diabetes.

Use of advanced statistical techniques to predict all-cause mortality in the Systolic Blood Pressure Intervention Trial

BackgroundThe Systolic Blood Pressure Intervention Trial (SPRINT) was conducted in patients with hypertension and additional risk for cardiovascular disease who were randomized to the intensive blood pressure group targeting systolic blood pressure (SBP) less than 120 mm Hg and to the standard group where the target was less than 140 mm Hg. Analyses were done in the matched group of participants with the same gender, same age (±2 years) and same SBP (±3 mm Hg) at three months of treatment regardless of initial randomization to intensive or standard group (shaded area in Figure 1). Methods and resultsDuring 3.26 years of follow-up, intensive group participants had 14.8 mm Hg lower SBP and received on average one more (2.8 vs. 1.8) blood pressure lowering medications. This was associated with lower all-cause mortality in the intensive treatment group (hazard ratio, 0.73; 95% CI, 0.60 to 0.90, p = 0.003). The effect on SBP was achieved at 3 months and remained unchanged thereafter. This paper addresses two questions with respect to all-cause mortality in SPRINT in the matched set. 1) What is the effect of receiving more than one drug on all-cause mortality. Conditional logistic regression for all-cause mortality with respect to number of drugs indicated that during the 3.26 years of follow-up persons who received more than one drug were more likely to die (coefficient = 0.5039, OR = 1.6552, p = 0.0322) than patients who received one drug. 2) Was there a U curve relationship between on treatment SBP and all-cause mortality? A U curve fitting a quadratic equation (parabola) of SBP and all-cause death was observed. This was seen in the patients randomized to the standard target group in unadjusted analyses as well as in analyses adjusted for demographics or all covariates (p < 0.001 for all). The U curves in the combined group and the intensive treatment group were less pronounced. ConclusionSPRINT participants who were matched for gender, age, and SBP at 3 months, and received more than one drug had higher all-cause mortality during the 3.26 years of follow-up. Those who were randomized to standard treatment target had a U curve relationship between SBP at three months and all-cause mortality. The U curves in the combined group and the intensive treatment group were less pronounced.

Kidney, Cardiac, and Safety Outcomes Associated With α-Blockers in Patients With CKD: A Population-Based Cohort Study

Alpha-blockers (ABs) are commonly prescribed for control of resistant or refractory hypertension in patients with and without chronic kidney disease (CKD). The association between AB use and kidney, cardiac, mortality, and safety-related outcomes in CKD remains unknown. Population-based retrospective cohort study. Ontario (Canada) residents 66 years and older treated for hypertension in 2007 to 2015 without a prior prescription for an AB. New use of an AB versus new use of a non-AB blood pressure (BP)-lowering medication. 30% or greater estimated glomerular filtration rate (eGFR) decline; dialysis initiation or kidney transplantation (kidney replacement therapy); composite of acute myocardial infarction, coronary revascularization, congestive heart failure, or atrial fibrillation; safety (hypotension, syncope, falls, and fractures) events; and mortality. New users of ABs (doxazosin, terazosin, and prazosin) were matched to new users of non-ABs by a high dimensional propensity score. Cox proportional hazards and Fine and Gray models were used to examine the association of AB use with kidney, cardiac, mortality, and safety outcomes. Interactions by eGFR categories (≥90, 60-89, 30-59, and<30mL/min/1.73m2) were explored. Among 381,120 eligible individuals, 16,088 were dispensed ABs and matched 1:1 to non-AB users. AB use was associated with higher risk for≥30% eGFR decline (HR, 1.14; 95% CI, 1.08-1.21) and need for kidney replacement therapy (HR, 1.28; 95% CI, 1.13-1.44). eGFR level did not modify these associations, P interaction=0.3and 0.3, respectively. Conversely, AB use was associated with lower risk for cardiac events, which was also consistent across eGFR categories (HR, 0.92; 95% CI, 0.89-0.95; P interaction=0.1). AB use was also associated with lower mortality risk, but only among those with eGFR<60mL/min/1.73m2 (P interaction<0.001): HRs were 0.85 (95% CI, 0.78-0.93) and 0.71 (95% CI, 0.64-0.80) for eGFR of 30 to 59 and<30mL/min/1.73m2, respectively. Observational design, BP measurement data unavailable. AB use in CKD is associated with higher risk for kidney disease progression but lower risk for cardiac events and mortality compared with alternative BP-lowering medications.

Patients With Type 2 Diabetes Have an Increased Demand for Pacemaker Treatment: A Comparison With Age- and Sex-Matched Control Subjects From the General Population.

Patients with type 2 diabetes have an increased risk for cardiovascular disease, including arrhythmias. The prevalence of bradyarrhythmia and the subsequent need for treatment with pacemakers (PMs) is less well explored in a contemporary patient population. The current study explores 1) whether patients with type 2 diabetes have an increased demand for PM implantation compared with an age- and sex-matched control population without diabetes and 2) patient characteristics associated with an increased demand for receiving a PM. In this population-matched registry study, a total of 416,247 patients with type 2 diabetes from the Swedish National Diabetes Registry and 2,081,235 age- and sex-matched control subjects selected from the general population were included between 1 January 1998 and 31 December 2012 and followed until 31 December 2013. Mean follow-up time was 7 years. Cox proportional hazards regression analyses were performed to estimate the demand of PM treatment and the factors identifying patients with such demand. Type 2 diabetes was associated with an increased need of PM treatment (hazard ratio 1.65 [95% CI 1.60-1.69]; P < 0.0001), which remained (1.56 [1.51-1.60]; P < 0.0001) after adjustments for age, sex, educational level, marital status, country of birth, and coronary heart disease. Risk factors for receiving a PM included increasing age, HbA1c, BMI, diabetes duration, and lipid- and blood pressure-lowering medication. The need for PM treatment is higher in patients with type 2 diabetes than in matched population-based control subjects. Age, diabetes duration, and HbA1c seem to be risk factors for PM treatment.

Blood pressure goal attainment in multi-ethnic Asian patients with hypertension and dyslipidaemia in primary care.

Hypertension and dyslipidaemia are major risk factors for cardiovascular diseases and achieving treatment goals mitigates such risks. This study determined demographic and medication-related factors associated with blood pressure (BP) goal attainment in patients with concomitant hypertension and dyslipidaemia. This paper is a sub-analysis of the Lipid HEALTH study, a questionnaire survey focusing on adult Asian patients with both dyslipidaemia and hypertension. An interviewer-administered questionnaire was used to obtain demographic and clinical information. Laboratory and prescription data was retrieved from electronic health records. BP goals were defined by international guidelines. Data was audited and analysed, and logistic regression analysis was used to identify factors determining BP goal attainment. Among the 851 included patients, 49.7% attained their BP goals. 37.0% were on monotherapy, 57.6% on ≥ 2 BP-lowering medications, and 5.4% had no pharmacologic treatment. Among those on pharmacotherapy, 51.2% failed to achieve BP goals. Calcium channel blockers were the most frequently prescribed medications. Attainment of BP goals was significantly associated with: not having Type 2 diabetes mellitus (odds ratio [OR] 2.27, 95% confidence interval [CI] 1.61-3.13); attaining low-density lipoprotein cholesterol goal (OR 2.02, 95% CI 1.45-2.81); being solely on dietary control (OR 2.19, 95% CI 1.09-4.39); and receiving monotherapy (OR 1.71, 95% CI 1.18-2.48). BP treatment goals were attained by half of the patients with dyslipidaemia and hypertension, and half of those on pharmacotherapy. Type 2 diabetes mellitus and low-density lipoprotein cholesterol control were significantly associated with BP goal attainment.

Theory-based mobile phone text messaging intervention for blood pressure control (TEXT4BP) among hypertensive patients in Nepal: study protocol for a feasibility randomised controlled trial

IntroductionUncontrolled blood pressure is one of the main risk factors for cardiovascular disease and death in Low-income and middle-income countries. Improvements to medication adherence and lifestyle changes can be assisted...

Absolute cardiovascular disease risk and the use of the Australian cardiovascular disease risk calculator.

Primary prevention of cardiovascular disease (CVD) has been traditionally guided by individual risk factors such hypertension and hypercholesterolaemia. An absolute risk-based approach is more effective. The aim of this article is to outline the superiority of an absolute risk-based approach when compared with individual risk factor management for the primary prevention of CVD, and to elaborate on the derivation and use of the Australian absolute CVD risk calculator. An absolute risk-based approach is superior to the traditional individual risk factor approach when identifying which patients would benefit most from the prescription of blood pressure-lowering and lipid-lowering medications.

May Measurement Month 2018: an analysis of blood pressure screening results from Australia.

May Measurement Month (MMM), originally initiated as a temporary solution to address the lack of blood pressure (BP) screening programs worldwide, emerged as an effective annual campaign to increase the awareness of hypertension. MMM18, a cross-sectional survey of volunteers aged ≥18 years was carried out during May 2018 predominantly in capital cities across Australia following the standard MMM protocol. Blood pressure screening along with additional information including anthropometric data and responses to questionnaires on demographic, lifestyle, and environmental factors were collected from 3 352 individuals across Australia. After multiple imputation, 1 026 (30.6%) adult Australians had hypertension. Of the 2 936 individuals not on antihypertensive treatment, 610 (20.8%) were hypertensive, and 237 (57.1%) of the 416 individuals receiving antihypertensive treatment had uncontrolled BP. In line with MMM17 results and other previous surveys, MMM18 revealed that close to one-third of the screened population (30.6%) had hypertension, 57.1% of individuals treated with BP-lowering medication remained uncontrolled indicating suboptimal management of the condition in the majority of patients. Most importantly, only 49.0% of those with hypertension were aware of their elevated BP, highlighting lack of awareness of elevated BP in nearly half of the affected population. Elevated BP was directly associated with alcohol consumption, overweight, and obesity. Our findings demonstrate the need for (i) continued efforts to increase BP awareness in the population, (ii) optimization of BP management strategies, and (iii) tackling some of the major contributors to BP elevation, including alcohol consumption and obesity.

May Measurement Month 2018: an analysis of blood pressure screening results from Nigeria.

Hypertension remains the dominant cardiovascular risk factor worldwide. May Measurement Month (MMM) is an annual global programme of the International Society of Hypertension aimed at screening for undetected hypertension in the general population. We report the outcome of MMM 2018 in Nigeria. An opportunistic screening of adults aged at least 18 years was conducted in the six geopolitical zones of Nigeria in the month of May, 2018. Screening for hypertension was done by trained volunteers with the use of validated digital and mercury sphygmomanometers following the MMM protocol. Hypertension was defined as blood pressure (BP) ≥140/90 mmHg or the use of BP-lowering medication. There were 6398 participants (53.0% female) with a mean (SD) age of 41.7 (15.0) years. Hypertension was present in 36.4% of the participants with 51.1% of the hypertensives aware of their status, 41.8% on medication, of whom 43.1% were controlled. Overall, only 18.0% of all hypertensive participants had their BP under control. The proportion with hypertension is high, and awareness, treatment, and control rates are low. Concerted efforts are needed to improve awareness and treatment of hypertension in Nigeria in order to reduce the high rate of complications associated with uncontrolled BP.

Validation of a Health System Measure to Capture Intensive Medication Treatment of Hypertension in the Veterans Health Administration

Blood pressure (BP) targets are the main measure of high-quality hypertension care in health systems. However, BP alone does not reflect intensity of pharmacological treatment, which should be carefully managed in older patients. To develop and validate an electronic health record (EHR) data-only algorithm using pharmacy and BP data to capture intensive hypertension care (IHC), defined as 3 or more BP medications and BP less than 120 mm Hg, and to identify conditions associated with greater IHC, either through greater algorithm false-positive IHC, or by contributing clinically to delivering more IHC. This cross-sectional study was conducted among 319 randomly selected patients aged 65 years or older receiving IHC from the Veterans Health Administration (VHA) from July 1, 2011, to June 30, 2013. Data were collected from a total of 3625 primary care visits. Data were analyzed from January 2017 to March 2020. Calibration and measurement of the algorithm for IHC (algorithm IHC). For each primary care visit, the reference standard, clinical IHC, was determined by detailed review of free-text clinical notes. The correlation in BP medication count between the EHR-only algorithm vs the reference standard and the sensitivity and specificity of the algorithm IHC were calculated. In addition, presence vs absence of contributing conditions acting in combination with hypertension management were measured to examine incidence of IHC associated with contributing conditions, including an acute condition that lowered BP (eg, dehydration), another condition requiring a BP target lower than the standard 140 mm Hg (eg, diabetes), or the patient needing a BP-lowering medication for a nonhypertension condition (eg, β-blocker for atrial fibrillation) resulting in low BP. Among 319 patients with 3625 visits (mean [SD] age, 75.6 [7.2] years; 3592 [99.1%] men), 911 visits (25.1%) had clinical IHC by the reference standard. The algorithm for determining medication count was highly correlated with the reference standard (r = 0.84). Sensitivity of detecting clinical IHC was 92.2% (95% CI, 89.3%-95.1%), and specificity was 97.2% (95% CI, 96.1%-98.3%), suggesting that clinical IHC can be identified from routinely collected data. Only 75 visits (2.1%) were algorithm IHC false positives, 55 visits (1.5%) involved IHC with contributing conditions, and 125 visits (3.5%) involved either false-positive or IHC with contributing conditions. Among select contributing conditions, congestive heart failure (37 patients [5.2%]) was most associated with a prespecified combined false-positive or IHC with contributing conditions rate higher than 5%. These findings suggest that health system data can be used reliably to estimate IHC.

The effect of feedback on cardiovascular risk factors on optimization of primary prevention: The PharmLines initiative

BackgroundIt is unknown whether population based single assessment of cardiovascular disease (CVD) risk and feedback to individuals and general practitioners results in initiation of preventive cardiovascular pharmacotherapy in those at risk. MethodsThe population based cohort study Lifelines was linked to the IADB.nl pharmacy database to assess information on the initiation of preventive medication (N = 48,770). At the baseline visit, information on cardiovascular risk factors was collected and reported to the participants and their general practitioners. An interrupted-time-series-analysis was plotted, in which the start year of blood pressure and lipid lowering medication was displayed in years before or after the baseline visit. Subsequently, predictors of the initiation of pharmacotherapy were determined and possible reduction in cardiovascular events that could be achieved by optimal treatment of individuals at risk. ResultsBefore the Lifelines baseline visit, 34% (out of 1,527, 95% Confidence interval (CI) 32%–36%) and 30% (out of 1,991, 95%CI 28%–32%) of the individuals at risk had a blood pressure or lipid lowering drug prescription, respectively. In those at risk, the use of blood pressure lowering medication, increased substantially during the year of the baseline visit. Treating individuals at increased risk (≥5% 10-year risk) with lipid or blood pressure lowering medication (N = 8515 and N = 6899) would have prevented 162 and 183 CVD events, respectively, in the upcoming five years. ConclusionPrimary prevention of CVD in the general population appears suboptimal. Feedback of cardiovascular risk factors resulted in a substantial increase of blood pressure lowering medication and extrapolated health benefits.

A genome-wide cross-phenotype meta-analysis of the association of blood pressure with migraine

Blood pressure (BP) was inconsistently associated with migraine and the mechanisms of BP-lowering medications in migraine prophylaxis are unknown. Leveraging large-scale summary statistics for migraine (Ncases/Ncontrols = 59,674/316,078) and BP (N = 757,601), we find positive genetic correlations of migraine with diastolic BP (DBP, rg = 0.11, P = 3.56 × 10−06) and systolic BP (SBP, rg = 0.06, P = 0.01), but not pulse pressure (PP, rg = −0.01, P = 0.75). Cross-trait meta-analysis reveals 14 shared loci (P ≤ 5 × 10−08), nine of which replicate (P < 0.05) in the UK Biobank. Five shared loci (ITGB5, SMG6, ADRA2B, ANKDD1B, and KIAA0040) are reinforced in gene-level analysis and highlight potential mechanisms involving vascular development, endothelial function and calcium homeostasis. Mendelian randomization reveals stronger instrumental estimates of DBP (OR [95% CI] = 1.20 [1.15–1.25]/10 mmHg; P = 5.57 × 10−25) on migraine than SBP (1.05 [1.03–1.07]/10 mmHg; P = 2.60 × 10−07) and a corresponding opposite effect for PP (0.92 [0.88–0.95]/10 mmHg; P = 3.65 × 10−07). These findings support a critical role of DBP in migraine susceptibility and shared biology underlying BP and migraine.

Night- Time Chronotherapy With Diuretics: Effect On Sleep Quality And Duration In Patients With Hypertension In Lusaka, Zambia

Poor sleep plays an important role in the prevalence of hypertension. It increases the prevalence rate to 60%. The night-time dosing of blood pressure-lowering drugs has yielded positive results. Scholars have rarely investigated the relationship between night-time dosing of diuretics and the quality of sleep. The study aimed at evaluating the quality and duration of sleep while on night-time dosing of diuretics and determine the commonly used blood pressure-lowering medication at University Teaching Hospital. The study was a Prospective Cohort Study with 12 weeks of follow-up. The sample consisted of 46 patients with hypertension and on a diuretic, 25 of whom were taking their medication in the evening at 10 PM (study group), and 18 were in the 10 AM dosing schedule as a control. Overall, 43 were included in the analysis. Baseline and follow-up at 2, 8 and 12 Sleep quality and duration, and blood pressure level were available for 43 (93.5%) individuals. The study recruited more women (76.1%) and the majority were on hydrochlorothiazide and amiloride combination (65.2%). The 10 PM dosing showed better quality of sleep and duration, and blood pressure-lowering as the follow-up continued with a p-value of less than 0.05 for Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS), and for the blood pressure-lowering at 12 weeks. The study showed beneficial effects of 10 PM dosing of diuretics in hypertensive patients and the diuretic effect does not affect the quality and duration of sleep. Further, 10 PM dosing lowers the blood pressure significantly compared with 10 AM.

Global Plasma Metabolomics to Identify Potential Biomarkers of Blood Pressure Progression.

The pathophysiology of hypertension remains incompletely understood. We investigated associations of circulating metabolites with longitudinal blood pressure (BP) changes in the Prospective Investigation of the Vasculature in Uppsala Seniors cohort and validated the findings in the Uppsala Longitudinal Study of Adult Men cohort. Approach and Results: Circulating metabolite levels were assessed with liquid- and gas-chromatography coupled to mass spectrometry among persons without BP-lowering medication at baseline. We studied associations of baseline levels of metabolites with changes in BP levels and the clinical BP stage between baseline and a follow-up examination 5 years later. In the discovery cohort, we investigated 504 individuals that contributed with 757 observations of paired BP measurements. The mean baseline systolic and diastolic BPs were 144 (19.7)/76 (9.7) mm Hg, and change in systolic and diastolic BPs were 3.7 (15.8)/-0.5 (8.6) mm Hg over 5 years. The metabolites associated with diastolic BP change were ceramide, triacylglycerol, total glycerolipids, oleic acid, and cholesterylester. No associations with longitudinal changes in systolic BP or BP stage were observed. Metabolites with similar structures to the 5 top findings in the discovery cohort were investigated in the validation cohort. Diacylglycerol (36:2) and monoacylglycerol (18:0), 2 glycerolipids, were associated with diastolic BP change in the validation cohort. Circulating baseline levels of ceramide, triacylglycerol, total glycerolipids, and oleic acid were positively associated with longitudinal diastolic BP change, whereas cholesterylester levels were inversely associated with longitudinal diastolic BP change. Two glycerolipids were validated in an independent cohort. These metabolites may point towards pathophysiological pathways of hypertension.

Clinical Characteristics and Outcomes of Patients With Diabetes and COVID-19 in Association With Glucose-Lowering Medication.

Diabetes is one of the most distinct comorbidities of COVID-19. Here, we describe the clinical characteristics of and outcomes in patients with diabetes in whom COVID-19 was confirmed or clinically diagnosed (with typical features on lung imaging and symptoms) and their association with glucose-lowering or blood pressure-lowering medications. In this retrospective study involving 904 patients with COVID-19 (136 with diabetes, mostly type 2 diabetes), clinical and laboratory characteristics were collected and compared between the group with diabetes and the group without diabetes, and between groups taking different medications. Logistic regression was used to explore risk factors associated with mortality or poor prognosis. The proportion of comorbid diabetes is similar between cases of confirmed and of clinically diagnosed COVID-19. Risk factors for higher mortality of patients with diabetes and COVID-19 were older age (adjusted odds ratio [aOR] 1.09 [95% CI 1.04, 1.15] per year increase; P = 0.001) and elevated C-reactive protein (aOR 1.12 [95% CI 1.00, 1.24]; P = 0.043). Insulin usage (aOR 3.58 [95% CI 1.37, 9.35]; P = 0.009) was associated with poor prognosis. Clinical outcomes of those who use an ACE inhibitor (ACEI) or angiotensin II type-I receptor blocker (ARB) were comparable with those of patients who do not use ACEI/ARB among COVID-19 patients with diabetes and hypertension. C-reactive protein may help to identify patients with diabetes who are at greater risk of dying during hospitalization. Older patients with diabetes were prone to death related to COVID-19. Attention needs to be paid to patients with diabetes and COVID-19 who use insulin. ACEI/ARB use showed no significant impact on patients with diabetes and hypertension who have COVID-19.

MON-205 Effectiveness of Pre-Op α-Blockade on Intra-Op Blood Pressure Control in Patients with Pheochromocytoma

Pheochromocytoma are rare tumors arising from catecholamine producing chromaffin tissue. Surgical manipulation of pheochromocytoma inevitably leads to supraphysiologic levels of circulating catecholamines. Such manipulation has the potential to lead to an intra-operative hypertensive crisis, cardiac arrhythmia, myocardial infarction, or pulmonary edema. When inadequately primed pre-operatively, a patient exposed to such surges may experience life-threatening consequences.Phenoxybenzamine is a non-competitive, non-selective α 1 and α 2 receptor antagonist that prevents blood pressure liability during surgical resection of pheochromocytoma. Previous literature has suggested that phenoxybenzamine affords more pronounced peri-operative systolic blood pressure control as compared to selective alpha-blockers. This superior control potentially is at the cost of postoperative hypotension owing to the irreversible nature of phenoxybenzamine.1Our study compares the effects of pre-operative phenoxybenzamine on perioperative outcomes at a single tertiary medical center from 2004 to 2019. The cumulative pre-operative phenoxybenzamine dose was compared to the maximum intra-operative blood pressure, need for IV blood pressure lowering medications, duration of vasopressor need, volume replacement need, duration of time in the OR, duration of hospital stay, and pre-operative catecholamine levels. We speculate that increased phenoxybenzamine exposure will result in reduced peak intra-operative blood pressure and need for IV blood pressure lowering medications but may increase the need for post-resection intra-operative vasopressors and post-resection volume replacement.After IRB approval, (ID #00031606), we performed a data warehouse query for the ICD 9 and 10 codes of “pheochromocytoma” and “paraganglioma”. Patients who did not have confirmed pheochromocytoma on pathology were excluded. Data was collected retrospectively on 30 patients who underwent adrenalectomy for pheochromocytoma. 14 charts were excluded due to incomplete intra-operative anesthetic documentation.Our results suggest that there is no significant correlation between peak intra-operative MAP and cumulative phenoxybenzamine exposure. The cumulative dose of pre-operative phenoxybenzamine did not correlate with the number of anti-hypertensive medications used intra-operatively. An increased cumulative dose of pre-operative phenoxybenzamine was not associated with an increased duration of intra-operative vasopressor medications. Intra-operative volume replacement needs were surprisingly reduced with increased cumulative pre-operative phenoxybenzamine exposure. 1 P.A. van der Zee, A. de Boer. Pheochromocytoma: A review on preoperative treatment with phenoxybenzamine or doxazosin. The Netherlands Journal of Medicine. May 2014; Vol. 72 No 4, 190-201.

Determining optimal strategies for primary prevention of cardiovascular disease: systematic review, cost-effectiveness review and network meta-analysis protocol

BackgroundDespite recent improvements in the burden of cardiovascular disease (CVD) in the UK, deaths from CVD are relatively high compared with other high-income countries. An estimated 7 million people in the UK are living with CVD, and the healthcare cost is approximately £11 billion annually. In more than 90% of cases, the risk of a first heart attack is thought to be related to modifiable risk factors including smoking, poor diet, lipidemia, high blood pressure, inactivity, obesity and excess alcohol consumption. The aim of the study is to synthesise evidence for the comparative effectiveness and cost-effectiveness of different interventions for the primary prevention of CVD.MethodsWe will systematically search databases (for example, MEDLINE (Ovid), Embase (Ovid), Cochrane Library) and the reference lists of previous systematic reviews for randomised controlled trials that assess the effectiveness and cost-effectiveness of any form of intervention aimed at adult populations for the primary prevention of CVD, including but not limited to lipid lowering medications, blood pressure lowering medications, antiplatelet agents, nutritional supplements, dietary interventions, health promotion programmes, physical activity interventions or structural and policy interventions. Interventions may or may not be targeted at high-risk groups. Publications from any year will be considered for inclusion. The primary outcome will be all cause mortality. Secondary outcomes will be cardiovascular diseases related mortality, major cardiovascular events, coronary heart disease, incremental costs per quality-adjusted life years gained. If data permits, we will use network meta-analysis to compare and rank effectiveness of different interventions, and test effect modification of intervention effectiveness using subgroup analyses and meta-regression analyses.DiscussionThe results will be important for policymakers when making decisions between multiple possible alternative strategies to prevent CVD. Compared to results from existing multiple separate pairwise meta-analyses, this overarching synthesis of all relevant work will enhance decision-making. The findings will be crucial to inform evidence-based priorities and guidelines for policies and planning prevention strategies of CVD.Systematic review registrationPROSPERO CRD42019123940.

Observational analyses from ADVANCE and ADVANCE-ON.

To explain, and document, the epidemiological work associated with the action in diabetes and vascular disease: preterax and diamicron-modified release controlled evaluation (ADVANCE) clinical trial. ADVANCE was designed as a randomized controlled multicentre factorial trial in high-risk patients with diabetes. The two interventions were blood pressure lowering medications versus placebo, and intensive glucose control versus standard glucose control. Following termination of the trial, an observational study of surviving participants, able to join, was mounted: the ADVANCE - observational study (ADVANCE-ON). Other epidemiological analyses that were undertaken treated the trial as a cohort study, including using biomarkers from the blood samples taken from ADVANCE subjects as risk exposures. More than 50 publications have reported epidemiological results from ADVANCE. The main results from ADVANCE-ON suggested attenuated benefits of ADVANCE's blood pressure lowering treatment on all-cause and cardiovascular death, but no such long-term benefits for intensive glucose control, although this did give persistent benefit for end-stage renal disease. The other epidemiological studies found, amongst other things, strong effects of NT-terminal pro-B-type natriuretic peptide and high-sensitivity cardiac troponin T on macrovascular events, microvascular events and all-cause death. Embedding post-randomization and epidemiological analyses into clinical trials is worthwhile and can be highly productive in advancing scientific knowledge.

Primary prevention efforts are poorly developed in people at high cardiovascular risk: A report from the European Society of Cardiology EURObservational Research Programme EUROASPIRE V survey in 16 European countries

European Action on Secondary and Primary Prevention by Intervention to Reduce Events (EUROASPIRE) V in primary care was carried out by the European Society of Cardiology EURObservational Research Programme in 2016-2018. The main objective was to determine whether the 2016 Joint European Societies' guidelines on cardiovascular disease prevention in people at high cardiovascular risk have been implemented in clinical practice. The method used was a cross-sectional survey in 78 centres from 16 European countries. Patients without a history of atherosclerotic cardiovascular disease either started on blood pressure and/or lipid and/or glucose lowering treatments were identified and interviewed ≥ 6 months after the start of medication. A total of 3562 medical records were reviewed and 2759 patients (57.6% women; mean age 59.0 ± 11.6 years) interviewed (interview rate 70.0%). The risk factor control was poor with 18.1% of patients being smokers, 43.5% obese (body mass index ≥30 kg/m2) and 63.8% centrally obese (waist circumference ≥88 cm for women, ≥102 cm for men). Of patients on blood pressure lowering medication 47.0% reached the target of <140/90 mm Hg (<140/85 mm Hg in people with diabetes). Among treated dyslipidaemic patients only 46.9% attained low density lipoprotein-cholesterol target of <2.6 mmol/l. Among people treated for type 2 diabetes mellitus, 65.2% achieved the HbA1c target of <7.0%. The primary care arm of the EUROASPIRE V survey revealed that large proportions of people at high cardiovascular disease risk have unhealthy lifestyles and inadequate control of blood pressure, lipids and diabetes. Thus, the potential to reduce the risk of future cardiovascular disease throughout Europe by improved preventive cardiology programmes is substantial.

Abstract P456: The Association Between Clonal Hematopoiesis Of Indeterminate Potential And Inflammatory Biomarkers Among Chronic Kidney Disease Patients

Introduction: Clonal hematopoiesis of indeterminate potential (CHIP) is an age-related disorder associated with increased risk of atherosclerotic cardiovascular disease (ASCVD). Mechanistic studies of CHIP implicate inflammatory pathways underlying this relationship. Although inflammation is a well-established component of chronic kidney disease (CKD), linked to both CKD progression and ASCVD in CKD patients, CHIP has not been investigated in a CKD setting. Objective: To estimate the prevalence of CHIP in patients with CKD and to examine the cross-sectional associations between CHIP and biomarkers that were previously related to CKD progression and ASCVD among CKD patients. Methods: The current study was conducted among 598 Chronic Renal Insufficiency Cohort (CRIC) study participants with whole-exome sequencing data and baseline measures of fibrinogen, interleukin (IL)-6, serum albumin, and tumor necrosis factor-α. CHIP was detected from sequencing data using MuTect2. CHIP was defined as the presence of a somatic hematologic malignancy-associated mutation with a variant allele frequency (VAF) of at least 2%. CHIP was also categorized ordinally by clone size as no CHIP, small CHIP clone (VAF&lt;10%), and large CHIP clone (VAF ≥10%). Ordinal logistic regression was used to test associations of CHIP with each biomarker in age- and multivariable-adjusted models. Multivariable models adjusted for age, sex, ancestry, body mass index, estimated glomerular filtration rate, systolic blood pressure, low-density lipoprotein cholesterol, fasting plasma glucose, and blood pressure, lipid, and glucose lowering medications. Results: CHIP was detected in a total of 28 individuals from the WES study (4.7%). Among those 70 years of age and older, we detected a CHIP prevalence of nearly 16%. As expected, participants with CHIP were older than those without CHIP (mean age: 67 and 58 years, respectively; P&lt;0.0001). Other demographic and clinical variables were similar between groups . Age-adjusted models showed strong associations between CHIP and both fibrinogen and IL-6 with odds ratios of 2.49 (95% CI: 1.09, 5.71) and 2.45 (95% CI: 1.05, 5.72), respectively. After multivariable adjustment, only fibrinogen remained associated with CHIP with an odds ratio of 4.70 (95% CI: 1.69, 13.0). Consistent with these findings, there was a strong dose-dependent association between CHIP clone size and fibrinogen in multivariable adjusted analyses (P for linear trend=0.009). Compared to those without CHIP, odds ratios for higher fibrinogen tertile were 3.0 (95% CI: 0.84, 11.3) and 4.7 (95% CI: 1.29, 16.7) among those with small and large CHIP clone sizes, respectively. Conclusions: CHIP prevalence was higher among CKD patients in the current study compared to previous estimates from the general population. Furthermore, a strong, dose-dependent association between CHIP and fibrinogen was identified.