Microcirculation and Macrocirculation in Hypertension: A Dangerous Cross-Link?

Microcirculation and macrocirculation are tightly interconnected into a dangerous cross-link in hypertension. Small artery damage includes functional (vasoconstriction, impaired vasodilatation) and structural abnormalities (mostly inward eutrophic remodeling). These abnormalities are major determinants of the increase in total peripheral resistance and mean blood pressure (BP) in primary hypertension, which in the long term induces large artery stiffening. In turn, large artery stiffening increases central systolic and pulse pressures, which are further augmented by wave reflection in response to the structural alterations in small resistance arteries. Finally, transmission of high BP and flow pulsatility to small resistance arteries further induces functional and structural abnormalities, thus leading to increased total peripheral resistance and mean BP, thus perpetuating the vicious circle. Hyperpulsatility, in addition to higher mean BP, exaggerates cardiac, brain, and kidney damages and leads to cardiovascular, cerebral, and renal complications. The dangerous cross-link between micro and macrocirculation can be reversed into a virtuous one by ACE (angiotensin-converting enzyme) inhibitors, sartans, and calcium channel blockers. These three pharmacological classes are more potent than β-blockers and diuretics for reducing arterial stiffness and small artery remodeling. The same ranking was observed for their effectiveness at reducing left ventricular hypertrophy, preserving glomerular filtration rate, and preventing dementia, suggesting that they can act beyond brachial BP reduction, by breaking the micro/macrocirculation vicious circle.

Night-time diastolic blood pressure variability relates to stroke recurrence in patients who had ischaemic stroke with small artery occlusion

Background and purposeThe association between blood pressure variability (BPV) and stroke recurrence among patients who had ischaemic stroke (IS) remains unclear. This study aimed to investigate the association between BPV and stroke recurrence in patients who had IS of large artery atherosclerosis (LAA) subtype and small artery occlusion (SAO) subtype.MethodsData from the BOSS (Blood Pressure and Clinical Outcome in Transient Ischemic Attack or Ischemic Stroke) study were examined. IS subtypes were diagnosed according to the Trial of Org 10172 in Acute Stroke Treatment criteria. BPV was performed by 24-hour ambulatory blood pressure monitoring and defined through SD of blood pressure. The primary outcome was stroke recurrence within 90 days after discharge. Multivariable Cox regression model was used to assess the association between BPV and stroke recurrence in patients who had IS of LAA subtype and SAO subtype.ResultsA total of 1390 patients who had IS from the BOSS study were included in the present study. Multivariable analysis suggests that 24-hour systolic BPV (SBPV) and night-time diastolic BPV (DBPV) were significantly associated with stroke recurrence among all patients who had IS (HR, 2.50, 95% CI 1.07 to 5.84; HR, 1.85, 95% CI 1.07 to 3.21, respectively). Night-time SBPV and night-time DBPV were significantly associated with stroke recurrence in patients with SAO subtype (HR, 2.77, 95% CI 1.07 to 7.15; HR, 3.60, 95% CI 1.39 to 9.29, respectively). However, in the adjusted model, only night-time DBPV remained significant in patients with SAO subtype (HR, 3.87, 95% CI 1.40 to 10.71). Similar results were not found in patients who had IS of LAA subtype.ConclusionsHigh night-time DBPV was associated with increased risk of stroke recurrence among patients who had IS of SAO subtype. The results of this study have implications for the secondary prevention management and future research of patients who had IS of SAO subtype. The association between BPV and stroke recurrence in patients who had IS of LAA subtype and SAO subtype should be investigated in larger, population-based studies.

Trimethylamine N-Oxide and Stroke Recurrence Depends on Ischemic Stroke Subtypes

Background and Purpose: Trimethylamine N-oxide (TMAO) has been recognized as a risk factor for cardiovascular disease. However, the role of TMAO in ischemic stroke remains unclear. As we know, ischemic stroke is a heterogeneous disease with variable pathogenesis. Hence, we aimed to investigate the association between TMAO and stroke recurrence according to etiology subtypes. Methods: A total of 10 756 ischemic stroke/transient ischemic attack patients from the Third China National Stroke Registry were enrolled, and 1-year follow-up data for stroke recurrence were analyzed. TOAST (Trial of ORG 10172 in Acute Stroke Treatment) criteria was used to classify the etiology subtypes. Plasma TMAO levels were quantified by liquid chromatography–mass spectrometry. The association between TMAO and stroke outcomes was analyzed using Cox regression models. We also conducted a meta-analysis on the association of TMAO levels and stroke risk. Results: Elevated TMAO level was independently associated with the risk of stroke recurrence (Q4 versus Q1: adjusted hazard ratio, 1.37 [95% CI, 1.15–1.64]) in multivariate Cox regression model. After stratification by TOAST subtypes, there was a significant association between TMAO and stroke recurrence in small artery occlusion subtype (adjusted hazard ratio, 1.43 [95% CI, 1.03–2.00]) but not in the others subtype (large-artery atherosclerosis, 1.19 [0.95–1.48]; cardioembolism, 1.54 [0.95–2.48]; others, 1.19 [0.98–1.44]). The meta-analysis reported on stroke recurrence for the highest versus lowest TMAO levels with a pooled hazard ratio of 1.66 (95% CI, 0.91–3.01) and similarly found an increased risk of stroke recurrence. Conclusions: Elevated TMAO level is associated with increased risk of stroke recurrence in patients with small artery occlusion subtype, but this association seems to be attenuated in large-artery atherosclerosis, cardioembolism, and others subtypes.

Vascular hemodynamics and blood pressure differences between young and older women

Background Cardiovascular disease is one of the main causes of death in the United States, and hypertension is a primary risk factor. Therefore, the primary causes of hypertension need to be identified so they may be addressed for treatment. The purpose of this study was to compare blood pressure with hemodynamic values and identify factors that may explain blood pressure differences between a cohort of healthy normotensive younger and older women. Methods Participants were 49 young (age: 33.8 ± 5.9) and 103 old (age: 65.8 ± 4) who were non-hypertensive, had no previous history of heart disease or type 2 diabetes, body mass index less than 30 kg/m2, normal electrocardiography response at rest and during exercise, nonsmokers, and no use of medications known to affect cardiovascular or metabolic function. Body composition measured by dual-energy X-ray absorptiometry. Hemodynamic values measured by non-invasive pulse wave velocity through radial artery tonometry. Markers of inflammation measured through blood sample analysis. Results Significant differences exist between young and old groups in %fat (P < 0.001), systolic blood pressure (SBP) (P = 0.001), large artery elasticity (P = 0.005), small artery elasticity (P < 0.001), systemic vascular resistance (P = 0.004), total vascular impedance (P < 0.001), estimated cardiac output (P < 0.001), and tumor necrosis factor-⍺ (TNF-⍺) (P < 0.001). Using ANCOVA the difference in SBP between age groups was no longer significant after adjusting for small artery elasticity (P < 0.001) and TNF-⍺ (P = 0.041). Conclusions These data demonstrate that blood pressure and vascular hemodynamic measures differ significantly between young and old women independent of body composition. Furthermore, these differences may be explained by the inflammation marker TNF-⍺ and/or small artery elasticity.

Platelet Endothelial Aggregation Receptor 1 Polymorphism Is Associated With Functional Outcome in Small-Artery Occlusion Stroke Patients Treated With Aspirin

Background: The role of genetic polymorphisms is important in defining the patient's prognosis and outcomes in coronary artery disease. The present study aimed to explore the association between platelet endothelial aggregation receptor 1 (PEAR1) rs12041331 polymorphism and the outcomes in patients with acute ischemic stroke treated with aspirin or dual antiplatelet therapy (DAPT) with clopidogrel.Methods: A total of 868 ischemic stroke patients admitted to our hospital from January 1, 2016 to December 30, 2018 were retrospectively studied. The Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification defined stroke subtypes. These patients were treated with aspirin alone or DAPT. The genotype distribution of PEAR1 rs12041331 single-nucleotide polymorphism (AA, AC, and CC) between different TOAST subtypes and treatment groups was assessed, and the clinical impact of genetic variants on functional outcomes defined by the National Institutes of Health Stroke Scale, modified Rankin Scale, and Barthel Index was analyzed using univariate and multivariate logistic regression models.Results: Among the 868 stroke patients, the PEAR1 AA genotype was 16%, GA was 47%, and GG was 36%. Forty-four percent had aspirin alone, and 56% had DAPT. Overall, the distribution of PEAR single-nucleotide polymorphism was not significant among the two treatment groups or subtypes of TOAST. In contrast, in patients treated with aspirin alone, PEAR1 AA tended to be higher in the small-artery occlusion (SAO) subtype when compared with the no-lacunar subtype, including cardioembolism and large-artery atherosclerosis. PEAR1 AA genotype was significantly associated with favorable functional outcomes at day 7 and discharge only in SAO patients treated with aspirin alone compared with the GG genotype. Multivariate regression models further suggested that AA genotype was independently associated with favorable outcomes in this group after being adjusted for three common stroke risk factors such as age, hypertension history, and C-reactive protein level [odds ratio (OR) 0.23, 95% confidence interval (CI), 0.07–0.64, P = 0.02 for 7-day National Institutes of Health Stroke Scale; OR 0.2, 95% CI, 0.06–0.66, P = 0.03 for 7-day modified Rankin Scale, and OR 0.25, 95% CI, 0.08–0.72, P = 0.03 for 7-day Barthel Index, respectively].Conclusion: The impact of PEAR1 rs12041331 polymorphism on aspirin depends on the TOAST subtype. PEAR1 AA carrier with SAO stroke is most sensitive to aspirin therapy. PEAR1 AA is an independent factor for the short-term functional outcomes in SAO patients treated with aspirin alone.Clinical Registration Number: 1800019911.

Prevalence and Clinical Correlates of Intracranial Dolichoectasia in Individuals With Ischemic Stroke

Background and Purpose: Acute ischemic stroke is a known complication of intracranial dolichoectasia (IDE). However, the frequency of IDE causing brain infarction is unknown. We aim to determine the prevalence and clinical correlates of IDE in acute ischemic stroke by employing an objective IDE definition for major intracranial arteries of the anterior and posterior circulation. Methods: Consecutive patients with acute ischemic stroke admitted to a tertiary-care hospital during a 4-month period were analyzed. Intracranial arterial diameter, length, and tortuosity were determined by semiautomatic vessel segmentation and considered abnormal if ≥2 SDs from the study population mean. Either ectasia (increased diameter) or dolichosis (increased length or tortuosity) of at least one proximal intracranial artery defined IDE. Symptomatic IDE was considered when the infarct was located in the territory supplied by an affected artery in the absence of any alternative pathogenic explanation. Multivariate models were fitted to determine IDE clinical correlates. Results: Among 211 cases screened, 200 patients (mean age 67±14 years, 47.5% men) with available intracranial vessel imaging were included. IDE was identified in 24% cases (5% with isolated ectasia, 9.5% with isolated dolichosis, and 9.5% with both ectasia and dolichosis). IDE was considered the most likely pathogenic mechanism in 12 cases (6% of the entire cohort), which represented 23.5% of strokes initially categorized as undetermined cause. In addition, 21% of small-artery occlusion strokes had the infarct territory supplied by a dolichoectatic vessel (3% of the entire cohort). IDE was independently associated with male sex (odds ratio, 4.2 [95% CI, 1.7–10.6]) and its component of ectasia was associated with advanced age (odds ratio, 3.5 [95% CI, 1.3–9.5]). Vascular risk profile was similar across patients with stroke with and without IDE. Conclusions: Our findings suggest that IDE is an arteriopathy frequently found in patients with acute ischemic stroke and is likely responsible for a sizable fraction of strokes initially categorized as of undetermined cause and perhaps also in those with small-artery occlusion.

Abstract P653: Intracranial Artery Calcification Variations by Stroke Subtypes

Introduction: Intracranial artery calcification (IAC) is a common radiological finding on Computed Tomography (CT) scan. Although IAC occurs with aging, it is uncertain whether IAC varies by stroke subtypes. Method: We included patients admitted to our hospital with acute stroke. We quantified calcification volume of both clinoid and siphon carotid arteries, vertebral arteries at the V4 segment, and the basilar artery using an in-house quantification tool for non-contrast brain CT. Stroke etiological subtypes were determined according to the Trial of Organon in Acute Stroke Trial (TOAST) classification system independent of the calcification quantification. Demographic and clinical information was extracted from the medical records. We determined the prevalence of IAC in 51% of patients. (31% anterior, 7% posterior, and 14 % in both circulations) Result: We included 694 patients with stroke history (mean age 68 ± 16, range 21-101, 55% women, 71% nonwhite or mixed). IAC was associated with male sex (OR 1.47 [95%-CI 1.41-2.08), older age (OR 1.05 [95%-CI, 1.04-1.06]), hypertension (OR 1.55 [95%-CI, 1.01-2.36], dyslipidemia (OR 1.54 [95%-CI, 1.06-2.25]), and smoking (OR 1.79 [95%-CI, 1.18-2.71]). Anterior IAC was associated with dyslipidemia (OR 1.57 [95%-CI, 1.08-2.28], smoking (1.9 [95%-CI, 1.25-2.88]), and older age (OR 1.05 [95%-CI, 1.36-1.66). Posterior IAC was associated with myocardial infarction (OR 1.58 [95%-CI, 1.01-2.47] and older age (OR 1.02 [95%-CI, 1.01-1.03]. In multivariate analyses, any IAC was associated with small artery disease stroke (OR 1.01[95%-CI, 1.41-3.98]). Stratifying by circulations, however, demonstrated that the association was only with posterior (OR 1.22[95%-CI, 1.02-2.28]) and not anterior IAC (OR 1.20[95%-CI, 0.86-1.1.69]). There was no association between IAC and intracranial large artery stenoses OR (1.22[95%-CI, 0.78-1.1.92]). Conclusion: IAC is a marker of arterial disease, and its prevalence relates to vascular risk factors and small artery disease strokes. Understanding the mechanism by which IAC may relate to small artery disease may help us understand small artery stroke physiopathology and discover novel therapies for its treatment.