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Cardiac sympathetic burden reflects Parkinson disease burden, regardless of high or low orthostatic blood pressure changes.

ABSTRACT: Reduced uptake of ¹²³I-meta-iodobenzylguanidine (¹²³I-MIBG) and orthostatic hypotension (OH) are independently associated with worse clinical outcomes of Parkinson's disease (PD). However, their interactive influence on PD has not been studied. The role of ¹²³I-MIBG myocardial uptake, as a biomarker of PD severity, was investigated, conditional on the mediating effects of OH. A total of 227 PD patients were enrolled. Their motor and nonmotor aspects were assessed with standardized tools. Global disease burden was estimated by averaging the scaled z-scores of the assessment tools. Every patient went through ¹²³I-MIBG scan, and OH was evaluated with the head-up tilt-test. The mediating role of orthostatic blood pressure changes (ΔBP) on the association between cardiac sympathetic denervation and disease burden was investigated. Low heart-to-mediastinum (H/M) ratio with less than 1.78 was seen in 69.6% of the patient population, and 22.9% of patients had OH. Low H/M ratio was associated with OH, and these patients had worse disease burden than subjects with normal ¹²³I-MIBG uptake (global composite z-score: normal ¹²³I-MIBG vs. abnormal ¹²³I-MIBG; -0.3 ± 0.5 vs. 0.1 ± 0.7; p < 0.001). The mediation models, controlled for age and disease duration, revealed that the delayed H/M ratio and global composite score were negatively associated, irrespective of orthostatic ΔBP. Adverse relationship between cardiac sympathetic denervation and disease burden was shown without any interference from orthostatic blood pressure fluctuations. This result suggested that extracranial cardiac markers might reflect disease burden, regardless of labile blood pressure influence.

SUBMITTER: Yoo SW

PROVIDER: S-EPMC8361133 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionExtracellular volume (ECV) predicts mortality in hemodialysis patients, but it is difficult to assess clinically. Peridialytic blood pressure (BP) measurements can help ECV assessment. Orthostatic BP is routinely measured clinically, but its association with ECV is unknown.MethodsIn a cohort of hypertensive hemodialysis patients, we measured posthemodialysis ECV/weight with bioimpedance spectroscopy and analyzed its association with post-HD orthostatic BP measurements obtained during routine care. Using linear and logistic regression, the primary outcomes were orthostatic BP change and orthostatic hypotension (OH) defined by systolic BP decrease of at least 20 mmHg or diastolic decrease of at least 10 mmHg. Model 1 controlled for sex, age, and diabetes. Model 2 additionally controlled for ultrafiltration rate and antihypertensive medications. We conducted sensitivity analysis using OH definition of systolic BP decrease of at least 30 mmHg.FindingsAmong 57 participants, mean orthostatic systolic BP change was -7.30 (20) mmHg and mean ECV/weight was 0.24 (0.04) L/kg. Post-HD ECV/weight was not associated with orthostatic systolic BP change (β = 8.2, p = 0.6). There were 16 participants with and 41 participants without OH. The ECV/weight did not differ between these groups (0.22 [0.04] vs. 0.24 [0.05] L/Kg, p = 0.09) and did not predict OH in logistic regression (OR 11, 4.04; 95% CI 0.2-671, 0.03-0.530 in the two models.) In a sensitivity analysis, ECV/weight was lower in the OH group (0.22 [0.03] vs. 0.25 [0.04] L/kg, p = 0.005), but this was accompanied by differences in sex and diabetes. Using logistic regression, there was no independent association between ECV/weight with OH.DiscussionOrthostatic systolic BP change after HD completion is not a reliable indicator of posthemodialysis ECV. When considering other factors associated with orthostatic BP, ECV/weight is not independently associated with OH. Although transient postdialytic differences in intravascular volume may be associated with OH, posthemodialysis OH does not necessarily indicate ECV depletion.

Project description:PurposeTo determine whether cardiac sympathetic denervation in idiopathic Parkinson disease (IPD) affects the left ventricle in a distinct regional pattern versus a more global pattern with use of carbon 11 (11C) meta-hydroxyephedrine (HED) positron emission tomography (PET).Materials and methodsThis prospective study was approved by the institutional review board and was compliant with HIPAA. Informed consent was obtained from all subjects. Cardiac PET was performed with 11C HED in 27 patients with IPD (20 men and seven women aged 50-74 years; mean age, 62 years±6 [standard deviation]). 11C HED retention indexes (RIs), which reflect nerve density and integrity, were determined. RIs for 33 healthy control subjects (15 men and 18 women aged 20-78 years; mean age, 47 years±17) were used as a control database. Patients with IPD were compared with control subjects by using z score analysis. Global and segmental measurements of sympathetic denervation were expressed as percentage extent, z score severity, and severity-extent product (SEP). Group comparisons were performed with the Student t test.ResultsThe mean 11C HED RI was 0.086 mL of blood per minute per milliliter tissue±0.015 for control subjects and 0.043 mL of blood per minute per milliliter tissue±0.016 for patients with IPD (P<0001). When compared with normative data from the control database, profound cardiac denervation (global extent>50%) was seen in most patients (19 of 27 patients, 70%). Four patients had normal 11C HED studies and four had mild denervation (global extent<25%). The mean global denervation extent was 62%±38, the mean severity z score was -2.7±1.2, and the mean SEP was -202±131 (range, -358 to 0). Segmental analysis revealed relative sparing of anterior and proximal septal segments (mean extent, 48%-51%; mean severity z score, -2.47 to -2.0; mean SEP, -167 to -139), with lateral and proximal inferior segments more severely affected (mean extent, 68%-73%; mean severity z score, -2.8 to -2.62; mean SEP, -271 to -230). Patients with normal findings or preserved denervation did not significantly differ in mean age (t=1.09) or disease duration (t=0.44) compared to patients with severe sympathetic denervation.ConclusionCardiac sympathetic denervation in IPD is extensive, with a segmental pattern that involves the proximal lateral left ventricular wall most severely, with relative sparing of the anterior and proximal septal walls.

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Cardiac sympathetic burden reflects Parkinson disease burden, regardless of high or low orthostatic blood pressure changes.

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