Aggressive Blood Pressure Lowering Research Articles

Reperfusion status and postoperative blood pressure in acute stroke patients after endovascular treatment.

An aggressive lowering of blood pressure (BP) could lead to neurological worsening, particularly of the area that has not been reperfused in acute stroke patients with large vessel occlusion (LVO). We sought to investigate the association of reperfusion status and BP course following mechanical thrombectomy (MT) with outcomes in LVO. Consecutive patients with LVO treated with MT between Jan 2020 to Jun 2021 were enrolled in a retrospective cohort study. Hourly systolic BP (SBP) and diastolic BP (DBP) were recorded for 72 h following MT and maximum SBP and DBP levels were identified. The Extended Thrombolysis in Cerebral Infarction (eTICI) scale was used to assess reperfusion extent. LVO patients were stratified in 2 groups based on reperfusion status: complete reperfusion (eTICI 3) and incomplete reperfusion (eTICI 2b/c). Three-month functional independence was defined as a modified Rankin Scale score of 0-2. A total of 263 acute ischemic stroke patients with LVO were retrospectively evaluated. Complete reperfusion was achieved in 210 patients (79.8%). Post-MT maximum SBP over 160 mmHg was significantly related to worse functional outcome (38.1% vs. 55.7%, p = 0.006), higher likelihood of in-hospital mortality and 3-month mortality (19.0% vs. 6.9%, p = 0.004, 27.4% vs. 14.3%, p = 0.012). No statistical correlation was found between reperfusion status and blood pressure level (p > 0.05). In patients with complete reperfusion, patients with an average BP 120-140 mmHg tends to have worse functional outcome compared with 100-120 mmHg (OR = 1.77, 95%CI: 0.97-3.23, p = 0.061). High maximum SBP levels following MT are associated with an increased likelihood of 3-month functional dependence and mortality. An average BP of 100-120 mmHg tends to have better functional independence in completely reperfused patients. The effect of intensive BP control on incomplete reperfusion still warrants further investigations.

Impact of Preprocedural Diastolic Blood Pressure on Outcomes in Patients Undergoing Percutaneous Coronary Intervention.

Recent US guidelines recommend lower blood pressure (BP) targets in hypertension, but aggressive lowering of diastolic BP (DBP) can occur at the expense of myocardial perfusion, particularly in the presence of coronary artery disease. We sought to establish the long-term impact of low DBP on mortality among patients undergoing percutaneous coronary intervention with well-controlled systolic BP. We analyzed data from 12 965 patients undergoing percutaneous coronary intervention between 2009 and 2018 from the Melbourne Interventional Group registry who had a preprocedural systolic BP of ≤140 mm Hg. Patients with ST-elevation myocardial infarction, cardiogenic shock, and out-of-hospital arrest were excluded. Patients were stratified into 5 groups according to preprocedural DBP: <50, 50 to 59, 60 to 69, 70 to 79, and ≥80 mm Hg. The primary outcome was long-term, all-cause mortality. Mortality data were derived from the Australian National Death Index. Patients with DBP<50 mm Hg were older with higher rates of diabetes, renal impairment, prior myocardial infarction, left ventricular dysfunction, peripheral and cerebrovascular disease (all P<0.001). Patients with DBP<50 mm Hg had higher 30-day (2.5% versus 0.7% for the other 4 quintiles; P<0.0001) and long-term mortality (median, 3.6 years; follow-up, 29% versus 11%; P<0.0001). Cox-regression analysis revealed that DBP<50 mm Hg was an independent predictor of long-term mortality (hazard ratio [HR], 1.55 [95% CI, 1.20-2.00]; P=0.001). In patients with well-controlled systolic BP undergoing percutaneous coronary intervention, low DBP (<50 mm Hg) is an independent predictor of long-term mortality.

Intensive care unit deaths among neurosurgery patients in a tertiary hospital in South Western Nigeria

Background: Neurosurgical patients are the most critical ICU admissions. While advancements in neurosurgical ICUs (NICU) have improved outcomes of care globally, ICU mortality remains a major clinical issue in developing nations. This study evaluates ICU mortalities of neurosurgical patients in a general ICU setting at the UNIOSUN Teaching Hospital, Osogbo, Nigeria.&#x0D; Method: Case records of neurosurgery patients who died in the ICU of UNIOSUN Teaching Hospital, Osogbo, South-Western, Nigeria from June 2012 to May 2022 were reviewed. Simple descriptive statistics of data on demographics, clinical diagnoses, management and outcome were done.&#x0D; Results: Mortality rate was 38.9% (84 of 216 admissions). Males were 67(79.8%) and the mean age was 41.5years (Range: 2-85years). The average duration of ICU stay was 3.5days (Range: 30minutes-20days). Most patients had severe traumatic brain injury (TBI) (62, 73.8%). This was followed by cerebrovascular diseases (12, 14.3%) and brain tumours (6, 7.1%). Two had brain abscess. One patient each had mixed subacute/chronic subdural haematoma and severe cervical spondylotic myelopathy. Of the 69 whose case files were found, 7(10.1%) had a diagnosis of brainstem death before eventual 'final' death after an average of 13.5 additional hours on mechanical life support. The identified secondary causes of death included raised ICP, sepsis, primary surgical haemorrhage, seizures, acute kidney injury, malignant hypertension, poor glycaemic control and aggressive blood pressure lowering. Only 1 patient had autopsy.&#x0D; Conclusion: Most ICU mortalities among neurosurgical patients were from severe TBI. The establishment of NICU is necessary to improve outcome of care of neurosurgical patients.

Abstract WP123: Machine Learning To Predict High Risk Adverse Events In Treatment Trials For Intracerebral Hemorrhage

Background: ICH clinical trials have shown that aggressive blood pressure (BP) lowering can lead to adverse events (AEs) such as renal failure (RF) or new stroke. These studies focused on whether the study intervention causes AEs on average. By combining trials, we estimate each individual’s risk of developing AEs with BP lowering. Methods: We augmented data from ATACH2 by adding patients from the observational ERICH study and performed propensity score matching with a radius (radius=0.4, ratio=1). We estimated the individualized counterfactual outcome of renal AEs using augmented ATACH2. ERICH had 127 patients (out of 1,706) with new onset of RF during hospital stay. ATACH2 had 68 patients (out of 1000) with renal AEs (recorded by MedDRA) within 7d. We built the counterfactual prediction model using a neural network model (FlexTENet). We extracted feature importance score using Shap Deep Explainer. Results: We borrowed 1,706 patients to augment ATACH2. The augmented cohort had 2706 patients in total. FlexTENet captured the heterogeneity fairly. For factual outcome prediction accuracy, the FlexTENet achieved the best area under precision-recall curve (0.203) and the area under receiver operating curve (0.703). High diastolic BP at admission and low platelets increased the counterfactual effect of BP reduction on occurrence of renal AEs. In addition, high systolic BP and high glucose decreased the counterfactual effect on the occurrence of renal AEs. Conclusions: Identifying treatment-related AEs at an individual level has rarely been studied. Our counterfactual machine learning shows potential to predict individual patient’s risk of treatment-related adverse events.

Referral Pathway for Hypertension with High Cardiovascular Risk: A Review

Hypertension is considered as a common and powerful contributor to all the major cardiovascular diseases (CVDs), including coronary disease, stroke, peripheral artery disease, renal disease, and heart failure. Results from the Framingham study indicated that high blood pressure (BP), even within what is regarded as the non-hypertensive range, imposes an increased risk of CVD. The median BP at which cardiovascular sequelae appeared in the Framingham study was 130/80 mmHg. Epidemiological data have shown that the risk of CVD rises with increasing BP levels, starting at ≥115/75 mmHg in a strong, independent, graded, and continuous manner. Early and aggressive BP lowering is mandatory as it can contribute to long-term CV risk reduction. According to the Framingham study data, 31% of strokes occur in patients with normal or high normal hypertension. Clinical trial data suggest that antihypertensive therapies, particularly those that block the renin-angiotensin-aldosterone system (RAAS), can reduce CVD risks at least partly independently of BP lowering, although a major controversy involves this question. An optimal strategy to reduce CV risk may include lifestyle modifications, promoting adherence to early and aggressive target level achievement, appropriate drug choice, and especially global risk reduction.

Changes in Cerebral Blood Flow and Diffusion-Weighted Imaging Lesions After Intracerebral Hemorrhage.

Intracerebral hemorrhage (ICH) is a common subtype of stroke and places a great burden on the family and society with a high mortality and disability rate and a poor prognosis. Many findings from imaging and pathologic studies have suggested that cerebral ischemic lesions visualized on diffusion-weighted imaging (DWI) in patients with ICH are not rare and are generally considered to be associated with poor outcome, increased risk of recurrent (ischemic and hemorrhagic) stroke, cognitive impairment, and death. In this review, we describe the changes in cerebral blood flow (CBF) and DWI lesions after ICH and discuss the risk factors and possible mechanisms related to the occurrence of DWI lesions, such as cerebral microangiopathy, cerebral atherosclerosis, aggressive early blood pressure lowering, hyperglycemia, and inflammatory response. We also point out that a better understanding of cerebral DWI lesions will be a key step toward potential therapeutic interventions to improve long-term recovery for patients with ICH.

Acute Hypertensive Response in Patients With Acute Intracerebral Hemorrhage: A Narrative Review.

To review the role of the acute hypertensive response in patients with intracerebral hemorrhage, current treatment options, and areas for further research. Review of the literature to assess 1) frequency of acute hypertensive response in intracerebral hemorrhage; 2) consequences of acute hypertensive response in clinical outcomes; 3) acute hypertensive response and secondary brain injury: hematoma expansion and perihematomal edema; 4) vascular autoregulation, safety data side effects of acute antihypertensive treatment; and 5) randomized clinical trials and meta-analyses. An acute hypertensive response is frequent in patients with acute intracerebral hemorrhage and is associated with poor clinical outcomes. However, it is not clear whether high blood pressure is a cause of poor clinical outcome or solely represents a marker of severity. Although current guidelines recommend intensive blood pressure treatment (<140 mm Hg) in patients with intracerebral hemorrhage, 2 randomized clinical trials have failed to demonstrate a consistent clinical benefit from this approach, and new data suggest that intensive blood pressure treatment could be beneficial for some patients but detrimental for others. Intracerebral hemorrhage is a heterogenous disease, thus, a one-fit-all approach for blood pressure treatment may be suboptimal. Further research should concentrate on finding subgroups of patients more likely to benefit from aggressive blood pressure lowering, considering intracerebral hemorrhage etiology, ultra-early randomization, and risk markers of hematoma expansion on brain imaging.

Hypertension, hypotension, longevity and dementia.

High blood pressure at midlife has been consistently identified as a risk factor for dementia in late life, while dementia onset is typically associated with a subsequent decline of blood pressure values. A previous meta-analysis of randomized controlled studies of anti-hypertensive treatment in old age has shown a borderline effect of active treatment in reducing the risk of dementia. The cognitive sub-studies of SPRINT (SPRINT-MIND) and of HOPE-3, published in 2019, were aimed at assessing the cognitive effect of aggressive antihypertensive treatment. In SRINT-MIND, that included subjects with high vascular risk, the risk of dementia (primary outcome) did not differ between groups, but the risk of mild cognitive impairment was significantly reduced in the treatment group. Conversely in HOPE-3, that included subjects with intermediate vascular risk, no significant cognitive effect was observed, with a trend for a better outcome in the placebo arm in the subgroup with lower baseline systolic blood pressure. These data add to observational studies showing detrimental cognitive effect of lower blood pressure values in very old subjects, with cognitive impairment, disability, and complex health problems. Regarding longevity, observational studies confirm protective effects of lower blood pressure values, although systolic blood pressure <130 mmHg are associated with greater mortality risk in subjects with cognitive and/or motor impairment. On the whole antihypertensive treatment might decrease the risk of cognitive impairment in older, robust, high vascular risk subjects. Yet the presence of cognitive impairment might modify the prognostic effect of antihypertensive treatment and advise against aggressive blood pressure lowering.

Age and sex differences in frontal lobe cerebral oxygenation in older adults—Normative values using novel, scalable technology: Findings from the Irish Longitudinal Study on Ageing (TILDA)

AimsNear-infrared spectroscopy (NIRS) is a non-invasive, easy to apply, optical technology for measuring cerebral blood oxygenation, but there is lack of comprehensive population data to aid interpretation and clinical use. Given the importance of cerebral perfusion in the context of evolving guideline recommendations for more aggressive lowering of blood pressure (BP) in hypertension, even in the oldest old, understanding of normative NIRS values is timely. We estimated normative values of cerebral oxygenation measured by NIRS in a large community-dwelling population sample of adults aged > = 50 years (n = 3110). We hypothesized that measurements would be attenuated by cardiovascular risk factors. MethodsData from Wave 3 of The Irish Longitudinal Study on Ageing (TILDA) was utilized. Frontal lobe cerebral oxygenation was continuously measured via a Portalite, while participants rested in the supine position. Beat-to-beat BP was measured simultaneously. Normative data was modelled using generalized additive models for location, scale, and shape (GAMLSS). Multivariate linear regressions were used to examine associations with cardiovascular risk factors. ResultsAll three measures of NIRS (TSI, O2Hb and HHb) declined with increasing age. O2Hb and HHb were significantly lower in males than females. Increased smoking, excess alcohol intake, a higher waist-hip ratio, diabetes, angina, congestive heart failure, transient ischemic attack and total cardiovascular disease burden were all associated with decreased cerebral oxygenation. ConclusionWe present for the first time, normative resting-state NIRS reference data from a large population, which contributes to clinical interpretation of NIRS and advances the use of NIRS as a standard clinical tool.

APOE genotype, hypertension severity and outcomes after intracerebral haemorrhage.

Intracerebral haemorrhage in the elderly is a severe manifestation of common forms of cerebral small vessel disease. Nearly 60% of intracerebral haemorrhage survivors will develop clinical manifestations of small vessel disease progression including recurrent haemorrhage, ischaemic stroke, dementia, late-life depression and gait impairment within 5 years. Blood pressure measurements following intracerebral haemorrhage are strongly associated with this risk. However, aggressive blood pressure lowering in the elderly carries substantial risks. In order to determine whether there might be an opportunity to select individuals at the highest risk for small vessel disease progression for aggressive blood pressure reduction, we investigated whether APOE gene variants ɛ2/ɛ4 modify the association between blood pressure and small vessel disease clinical progression after intracerebral haemorrhage. We conducted a single-centre longitudinal study at a tertiary care referral centre (Massachusetts General Hospital in Boston, MA, USA), analysing 716 consecutive survivors of acute intracerebral haemorrhage, enrolled from January 2006 to December 2016. We conducted research interviews at the time of enrolment and obtained APOE genotypes from peripheral venous blood samples. We followed patients longitudinally by means of validated phone-based research encounters, aimed at gathering measurements of systolic and diastolic blood pressure, as well as information on small vessel disease clinical outcomes (including recurrent haemorrhage, incident ischaemic stroke, incident dementia, incident depression and incident gait impairment). APOE ε4 and systolic blood pressure were associated with the risk of recurrent haemorrhage, ischaemic stroke and post-haemorrhage dementia, depression and gait impairment (all P < 0.05). APOE ε4 and systolic blood pressure interacted to increase the risk of recurrent haemorrhage, ischaemic stroke, dementia and gait impairment (all interaction P < 0.05). Among patients with elevated blood pressure following intracerebral haemorrhage (average systolic blood pressure 120–129 mmHg and diastolic blood pressure <80 mmHg) only those with one or more APOE ε4 copies were at increased risk for one or more small vessel disease outcomes (hazard ratio = 1.97, 95% confidence interval 1.17–3.31). Among haemorrhage survivors with hypertension (stage 1 and beyond) APOE genotype also stratified risk for all small vessel disease outcomes. In conclusion, APOE genotype modifies the already strong association of hypertension with multiple small vessel disease clinical outcomes among intracerebral haemorrhage survivors. These data raise the possibility that genetic screening could inform blood pressure treatment goals in this patient population.

Acute medical management of aortic dissection.

Acute aortic dissection is a life-threatening disease. Current therapeutic guidelines recommend medical therapy with aggressive blood pressure lowering for patients with acute aortic dissection, when they are not indicated for emergency surgery. In particular, patients with aortic dissection without ascending aorta involvement (Stanford type B) are treated medically, unless they have fatal complications. Patients with type B aortic dissection who have critical complications have higher early mortality than that in patients without complications. However, recent advances in thoracic endovascular aortic repair can improve the clinical outcomes in such patients. Accordingly, current guidelines recommend thoracic endovascular aortic repair for patients with complicated type B aortic dissection. However, patients with visceral ischemia still have a poor prognosis, even when they are treated with thoracic endovascular aortic repair; an early diagnosis and intervention is crucial to prevent mortality. Understanding the pathophysiological anatomy that can induce organ malperfusion might be important for an early diagnosis and intervention. This review summarizes the current state of acute medical management in patients with acute aortic dissection, based on current evidence and expert consensus, focusing on patients with type B aortic dissection.

Effect Modification by Age on the Benefit or Harm of Antihypertensive Treatment for Elderly Hypertensives: A Systematic Review and Meta-analysis.

The influence of age on balance of benefit vs. potential harm of blood pressure (BP)-lowering therapy for elderly hypertensives is unclear. We evaluated the modifying effects of age on BP lowering for various adverse outcomes in hypertensive patients older than 60 years without specified comorbidities. All relevant randomized controlled trials (RCTs) were systematically identified. Coronary heart disease, stroke, heart failure (HF), cardiovascular death, major adverse cardiovascular events (MACE), renal failure (RF), and all-cause death were assessed. Meta-regression analysis was used to explore the relationship between achieved systolic BP (SBP) and the risk of adverse events. Random-effects meta-analysis was used to pool the estimates. Our study included 18 RCTs (n = 53,993). Meta-regression analysis showed a lower achieved SBP related with a lower risk of stroke and cardiovascular death, but an increased risk of RF. The regression slopes were comparable between populations stratifying by age 75 years. In subgroup analysis, the relative risks of a more aggressive BP lowering strategy were similar between patients aged older or less than 75 years for all outcomes except for RF (P for interaction = 0.02). Compared to treatment with final achieved SBP 140-150 mm Hg, a lower achieved SBP (<140 mm Hg) was significantly associated with decreased risk of stroke (relative risk = 0.68; 95% confidence interval = 0.55-0.85), HF (0.77; 0.60-0.99), cardiovascular death (0.68; 0.52-0.89), and MACE (0.83; 0.69-0.99). To treat hypertension in the elderly, age had trivial effect modification on most outcomes, except for renal failure. Close monitoring of renal function may be warranted in the management of elderly hypertension.

Target blood pressure and kidney protection

For many years, low on-treatment blood pressure values were widely regarded as necessary to maximise renal protection in individuals with high blood pressure. This notion was generated by several lines of evidence. Findings suggested that low blood pressure values could diminish or eliminate glomerular protein excretion, 1 Mancia G Schumacher H Redon J et al. Blood pressure targets recommended by guidelines and incidence of cardiovascular and renal events in the Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial (ONTARGET). Circulation. 2011; 124: 1727-1736 Crossref PubMed Scopus (137) Google Scholar which might lead to renal damage. Furthermore, the kidney can autoregulate its blood flow effectively over a wide range of blood pressure values, lessening concerns that low blood pressure might trigger renal underfusion, renal ischaemia, and a J-shaped relation with cardiac events. 2 Mancia G Grassi G Aggressive blood pressure lowering is dangerous: the J-curve. Hypertension. 2014; 63: 29-36 Crossref PubMed Scopus (89) Google Scholar Finally, in clinical studies, a progressive reduction in the glomerular filtration rate was attenuated in patients with intense treatment-induced blood pressure reductions versus less intense lowering of blood pressure, 3 Jafar TH Stark PC Schmid CH et al. Progression of chronic kidney disease: the role of blood pressure control, proteinuria, and angiotensin-converting enzyme inhibition: a patient-level meta-analysis. Ann Intern Med. 2003; 139: 244-252 Crossref PubMed Scopus (957) Google Scholar which also seemed to occur in patients with pronounced proteinuria. In the Modification of Diet in Renal Disease study in patients with non-diabetic nephropathy, 4 Peterson JC Adler S Burkart JM et al. Blood pressure control, proteinuria, and the progression of renal disease: the Modification of Diet in Renal Disease Study. Ann Intern Med. 1995; 123: 754-762 Crossref PubMed Scopus (1228) Google Scholar cutting mean arterial pressure to 92 mm Hg rather than 107 mm Hg was associated with a lesser decline in renal function in the subgroup of individuals with urinary protein excretion greater than 3 g/day. Intensive systolic blood pressure control and incident chronic kidney disease in people with and without diabetes mellitus: secondary analyses of two randomised controlled trialsIntensive lowering of systolic blood pressure increased the risk of incident chronic kidney disease in people with and without type 2 diabetes. However, the absolute risk of incident chronic kidney disease was higher in people with type 2 diabetes. Our findings suggest the need for vigilance in monitoring kidney function during intensive antihypertensive drug treatment, particularly in adults with diabetes. Long-term studies are needed to understand the clinical implications of antihypertensive treatment-related reductions in eGFR. Full-Text PDF

Blood pressure indices and cardiovascular disease mortality in persons with or without diabetes mellitus.

We examined the associations between blood pressure indices (SBP, DBP, mean arterial pressure and pulse pressure) and cardiovascular disease (CVD) mortality among persons with or without diabetes mellitus (NON-DM) in a multiethnic cohort. We included 17 650 participants from National Health and Nutrition Examination Survey III and 1439 participants from Diabetes Heart Study (total n = 19 089, 16.3% had diabetes mellitus, mean age 48.5 years, 44.4% white, 27.1% black, 28.5% other race, 54.4% women). Cox proportional hazard, cubic spline and area under the curve analyses were used to assess the associations. CVD death was ascertained via social security registry or the National Death Index. After a mean (SD) of 16.2 (6.1) years of follow-up, 17.9% of diabetes mellitus and 8.8% of those NON-DM died of CVD. Diabetes mellitus was associated with an increased risk of CVD death [hazard ratio (95% confidence interval): 1.50 (1.25-1.82)]. One SD increase in SBP was significantly associated with CVD mortality in NON-DM [1.28 (1.18-1.39)] but not diabetes mellitus [1.04 (0.88-1.23)] in the full Cox models. Adjusted cubic spline analysis showed significant nonlinear but different association between SBP and CVD mortality among diabetes mellitus (U-shaped) and NON-DM (J-shaped). The C-statistics of our full model in NON-DM and diabetes mellitus were (0.888 vs. 0.735, P < 0.001). SBP showed a trend toward improving C statistics in NON-DM but not diabetes mellitus. The association between SBP and CVD mortality risk is nonlinear but different in diabetes mellitus (U-shaped) and NON-DM (J-shaped), explaining why aggressive blood pressure lowering may have different outcomes in these two groups.

Update on the Therapeutic Strategy of Type B Aortic Dissection.

Stanford type B aortic dissection (TBAD) is a life-threatening disease. Current therapeutic guidelines recommend medical therapy with aggressive blood pressure lowering for patients with acute TBAD unless they have fatal complications. Although patients with uncomplicated TBAD have relatively low early mortality, aorta-related adverse events during the chronic phase worsen the long-term clinical outcome. Recent advances in thoracic endovascular aortic repair (TEVAR) can improve clinical outcomes in patients with both complicated and uncomplicated TBAD. According to present guidelines, complicated TBAD patients are recommended for TEVAR. However, the indication in uncomplicated TBAD remains controversial. Recent results of randomized trials, which compared the clinical outcome in patients treated with optimal medical therapy and those treated with TEVAR, suggest that preemptive TEVAR should be considered in uncomplicated TBAD with suitable aortic anatomy. However, these trials failed to show improvement in early mortality in patients treated with TEVAR compared with patients treated with optimal medical therapy, which suggest the importance of patient selection for TEVAR. Several clinical and imaging-related risk factors have been shown to be associated with early disease progression. Preemptive TEVAR might be beneficial and should be considered for high-risk patients with uncomplicated TBAD. However, an interdisciplinary consensus has not been established for the definition of patients at high-risk of TBAD, and it should be confirmed by experts including physicians, radiologists, interventionalists, and vascular surgeons. This review summarizes the current understanding of the therapeutic strategy in patients with TBAD based on evidence and expert consensus.

PREDICTORS OF ATRIAL FIBRILLATION AFTER CATHETER ABLATION IN A HYPERTENSIVE POPULATION: A SUB-STUDY OF SMAC-AF

Radiofrequency ablation for atrial fibrillation (AF) has emerged as a valuable therapy option; however, high rates of AF recurrence after ablation remain a limitation of this procedure. The recent Substrate Modification with Aggressive Blood Pressure Control (SMAC-AF) randomized controlled trial enrolled hypertensive patients, defined as BP>130/80mmHg, who had either persistent or paroxysmal AF, resistant or intolerant to at least one class I or III antiarrhythmic drug, who were scheduled for catheter ablation. 173 patients were randomly assigned to standard-of-care blood pressure target, 140/90mmHg or aggressive target, 120/80mmHg; there was no reduction in recurrence (HR 0.94, 95% CI 0.65-1.38 for aggressive control). This post-hoc analysis of the SMAC-AF population aimed to compare the risk factors for AF recurrence in each of the two cohorts. Using the SMAC-AF cohorts, we investigated how baseline characteristics and serum NT-pro-brain-natriuretic-peptide measured after AF ablation were associated with AF recurrence, defined as >30s of AF, more than 3 months post-ablation. Univariate Cox regression analysis was used to determine association between variables and AF recurrence. Of the 173 patients, 88 were randomized to the aggressive cohort, and 85 into the standard group. 106 (61.3%) patients had AF recurrence and 67 (38.7%) patients did not. Table 1 shows variables associated with AF recurrence. In the standard group, age (HR 1.03, p=0.04), number of antihypertensive medications (HR 1.31, p=0.048), and use of a calcium channel blocker (HR 1.81, p=0.03) were associated with recurrence. Twelve month NT-proBNP ≥300pg/ml was associated with higher AF recurrence as well. In the aggressive cohort, baseline systolic blood pressure (SBP) (HR 1.03, p=0.02), baseline SBP ≥ 140mmHg (HR 2.14, p=0.01), complex ablation during initial procedure (HR 3.11, p=0.01) were associated with recurrence, while use of diuretic (HR 0.44, p=0.01) was associated with reduced recurrence. There was a trend towards a reduction in occurrence with more anti-hypertensive agents (HR 0.81, p=0.08). An elevated baseline NT-proBNP had a trend towards association with recurrent AF; there were too few patients with an NT-proBNP ≥300pg/ml at 12 months (n=7 in the aggressive group) to determine significance in this group. In this post-hoc analysis, variables associated with recurrent AF differed between the aggressive and standard groups. Although aggressive blood pressure lowering was not associated with an improvement in AF recurrence in the entire cohort, there may be benefit in patients with higher baseline NT-proBNP, and older age. These associations need to be further clarified in ongoing clinical studies.

Recent Insights into Pharmacologic Cardiovascular Risk Reduction in Type 2 Diabetes Mellitus.

Diabetes mellitus (DM) affects nearly 30 million Americans and carries an increased risk of macrovascular complications of myocardial infarction, stroke, and cardiovascular death. While aggressive cardiovascular risk factor reduction has long been advocated in patients with diabetes, clinical trials have only recently demonstrated that such reductions result in improved outcomes. This review discusses recent evidence for risk reduction strategies and therapies with a focus on the management of glycemia, dyslipidemia, and hypertension. Although the degree to which aggressive glycated hemoglobin reduction decreases the risk of macrovascular outcomes remains unclear, the use of specific agents, such as the newer sodium glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) agonists, may reduce cardiovascular events in patients with diabetes, irrespective of glycated hemoglobin reduction. Statins have been the mainstay of dyslipidemia management, with recent guidelines recommending statin use in all patients aged 40-75years with diabetes. There is an emerging role for the recently developed proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in diabetes, as these agents further reduce serum cholesterol and clinical cardiovascular events beyond the maximum tolerated statin therapy. Lastly, most evidence suggests that aggressive blood pressure lowering in diabetic patients with hypertension reduces macrovascular events. Recent studies have re-affirmed a goal blood pressure of 140/90, and a lower pressure is likely prudent in most patients with diabetes. Specifically, angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) may reduce cardiovascular risk in patients with diabetes beyond their blood pressure-lowering effect. In conclusion, there is a growing literature which shows that the risk of cardiovascular outcomes can be reduced in most patients with diabetes, as outlined in this review.

Hypertensive crisis

Here, we review current concepts on hypertensive crisis (HTN-C) with a focus on epidemiology, causes, pathophysiology and prognosis. We also offer a practical approach to the management of HTN-C. HTN-C is characterized by a severe and abrupt increase in blood pressure (BP) with impending or progressive acute end-organ damage (EOD). HTN-C can be divided into hypertensive emergency (HTN-E) and hypertensive urgency (HTN-U) based on the presence or absence of acute EOD, respectively. Recent retrospective studies have demonstrated that emergency department (ED) referrals from an outpatient clinic or rapid BP-lowering strategies in the ED do not lead to improved outcomes in patients with HTN-U. HTN-C can be a de-novo manifestation or a complication of essential or secondary HTN. The presence of acute EOD is a major poor prognostic indicator in HTN-C. The main objectives of the management of HTN-C are distinction of HTN-E from HTN-U and appropriate risk stratification, prevention or regression of acute EOD due to severely elevated BP, prevention of recurrence of HTN-C with an effective long-term management plan and avoidance of rapid lowering of BP except in some special circumstances. The majority of patients with asymptomatic HTN-U can be safely managed in the outpatient setting without exposing them to the risks of aggressive BP lowering. However, patients with HTN-E require hospitalization, prompt treatment and close monitoring.

Effect of Aggressive Blood Pressure Control on the Recurrence of Atrial Fibrillation After Catheter Ablation: A Randomized, Open-Label Clinical Trial (SMAC-AF [Substrate Modification With Aggressive Blood Pressure Control]).

Radiofrequency catheter ablation for atrial fibrillation has become an important therapy for AF; however, recurrence rates remain high. We proposed to determine whether aggressive blood pressure (BP) lowering prevents recurrent atrial fibrillation (AF) after catheter ablation in patients with AF and a high symptom burden. We randomly assigned 184 patients with AF and a BP >130/80 mm Hg to aggressive BP (target <120/80 mm Hg) or standard BP (target <140/90 mm Hg) treatment before their scheduled AF catheter ablation. The primary outcome was symptomatic recurrence of AF/atrial tachycardia/atrial flutter lasting >30 seconds, determined 3 months beyond catheter ablation by a blinded end-point evaluation. The median follow-up was 14 months. At 6 months, the mean systolic BP was 123.2±13.2 mm Hg in the aggressive BP treatment group versus 135.4±15.7 mm Hg (P<0.001) in the standard treatment group. The primary outcome occurred in 106 patients, 54 (61.4%) in the aggressive BP treatment group compared with 52 (61.2%) in the standard treatment group (hazard ratio=0.94; 95% confidence interval, 0.65-1.38; P=0.763). In the prespecified subgroup analysis of the influence of age, patients ≥61 years of age had a lower primary outcome event rate with aggressive BP (hazard ratio=0.58; 95% confidence interval, 0.34-0.97; P=0.013). There was a higher rate of hypotension requiring medication adjustment in the aggressive BP group (26% versus 0%). In this study, this duration of aggressive BP treatment did not reduce atrial arrhythmia recurrence after catheter ablation for AF but resulted in more hypotension. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00438113.

Abstract WMP57: Declining Blood Pressure is Associated with Subcortical Microinfarcts in Older Adults

Hypertension is highly prevalent in the elderly population and microinfarcts are the most common vascular brain pathology identified in older adults at autopsy. We investigated the associations between systolic and diastolic blood pressures measured antemortem and the presence of microinfarcts at autopsy. Study subjects (n=302; age range=71-95) were participants in the population-based Mayo Clinic Study of Aging autopsy study, who had blood pressure measurements recorded during life. We investigated both cross-sectional systolic and diastolic blood pressure measurements at the baseline visit and the change in blood pressure (slope). Presence and location (subcortical or cortical) of chronic microinfarcts was abstracted from the autopsy reports. Of the 302 study subjects, 47 (16%) had cerebral microinfarcts, and, of those, 18 (38%) had subcortical microinfarcts and 29 (62%) had only cortical microinfarcts. The baseline blood pressures were not different between subjects with no microinfarcts, subcortical microinfarcts, and only cortical microinfarcts. In a logistic regression model including time between last blood pressure measurement and death, a greater decline in systolic [OR= 1.06 (1.01, 1.11); p=0.02]) and greater decline in diastolic [OR= 1.11 (1.02, 1.20); p=0.01] blood pressures were predictors of the presence of subcortical microinfarcts at autopsy. However, these variables were not associated with the presence of cortical microinfarcts. In conclusion, microinfarcts are common in the older adult population, and most of them are located in the cortex. A greater decline in both systolic and diastolic blood pressures and their association with subcortical microinfarcts, but not with cortical microinfarcts, may have implications for aggressive lowering of blood pressure in the elderly population.