Arterial hypertension in the chronic evolution of migraine: bystander or risk factor? An overview.

BACKGROUND: Several risk factors are associated with the chronic evolution of migraine. Clinical and preclinical studies have provided data about the role of hypertension (HT) as one of the potential modifiable risk factors of chronic migraine (CM). This review is focused on the biological and clinical evidence supporting common mechanisms underlying HT and migraine and the potential role of HT in the transition from episodic to chronic migraine. METHODS: We conducted a narrative review from a literature search covering the available evidence from studies investigating: i) the role of HT in the transition to CM in clinical practice; ii) the biological mechanisms potentially underpinning the association between HT and evolution to CM; iii) the role of antihypertensive medications in migraine prophylaxis. RESULTS: HT proved to be at the base of multiple mechanisms underlying migraine and migraine chronicization. Endothelial dysfunction, blood-brain barrier alterations, calcitonin gene-related peptide signaling, and renin-angiotensin-aldosterone system dysregulation are involved in the worsening effect of HT on migraine frequency, and the role of HT in the transition to CM is supported by clinical observations. CONCLUSIONS: The observed evidence supports HT contribution to CM evolution due to shared pathophysiologic mechanisms. While a bidirectional influence appears to be ascertained, data are still lacking about the one-way role of HT as direct risk factor for CM transition. Further research is needed to confirm a causal role of HT in this process.

Advancing Italian biomedical information extraction with transformers-based models: Methodological insights and multicenter practical application.

The introduction of computerized medical records in hospitals has reduced burdensome activities like manual writing and information fetching. However, the data contained in medical records are still far underutilized, primarily because extracting data from unstructured textual medical records takes time and effort. Information Extraction, a subfield of Natural Language Processing, can help clinical practitioners overcome this limitation by using automated text-mining pipelines. In this work, we created the first Italian neuropsychiatric Named Entity Recognition dataset, PsyNIT, and used it to develop a Transformers-based model. Moreover, we collected and leveraged three external independent datasets to implement an effective multicenter model, with overall F1-score 84.77 %, Precision 83.16 %, Recall 86.44 %. The lessons learned are: (i) the crucial role of a consistent annotation process and (ii) a fine-tuning strategy that combines classical methods with a "low-resource" approach. This allowed us to establish methodological guidelines that pave the way for Natural Language Processing studies in less-resourced languages.

A Call for Drug Therapies for the Treatment of Social Behavior Disorders in Dementia: Systematic Review of Evidence and State of the Art.

Growing evidence supports the presence of social cognition deficits and social behavior alterations in major and minor neurocognitive disorders (NCDs). Even though the ability to identify socio-emotional changes has significantly improved in recent years, there is still no specific treatment available. Thus, we explored evidence of drug therapies targeting social cognition alterations in NCDs. Papers were selected according to PRISMA guidelines by searching on the PubMed and Scopus databases. Only papers reporting information on pharmacological interventions for the treatment of social cognition and/or social behavioral changes in major and/or minor NCDs were included. Among the 171 articles entered in the paper selection, only 9 papers were eligible for the scope of the review. Trials testing pharmacological treatments for socio-emotional alterations in NCDs are poor and of low-medium quality. A few attempts with neuroprotective, psychoactive, or immunomodulating drugs have been made. Oxytocin is the only drug specifically targeting the social brain that has been tested with promising results in frontotemporal dementia. Its beneficial effects in long-term use have yet to be evaluated. No recommendation can currently be provided. There is a long way to go to identify and test effective targets to treat social cognition changes in NCDs for the ultimate benefit of patients and caregivers.

Bisdemethoxycurcumin (BDC)-Loaded H-Ferritin-Nanocages Mediate the Regulation of Inflammation in Alzheimer's Disease Patients.

BACKGROUND: Bisdemethoxycurcumin (BDC) might be an inflammation inhibitor in Alzheimer's Disease (AD). However, BDC is almost insoluble in water, poorly absorbed by the organism, and degrades rapidly. We thus developed a new nanoformulation of BDC based on H-Ferritin nanocages (BDC-HFn). METHODS: We tested the BDC-HFn solubility, stability, and ability to cross a blood-brain barrier (BBB) model. We tested the effect of BDC-HFn on AD and control (CTR) PBMCs to evaluate the transcriptomic profile by RNA-seq. RESULTS: We developed a nanoformulation with a diameter of 12 nm to improve the solubility and stability. The comparison of the transcriptomics analyses between AD patients before and after BDC-HFn treatment showed a major number of DEG (2517). The pathway analysis showed that chemokines and macrophages activation differed between AD patients and controls after BDC-HFn treatment. BDC-HFn binds endothelial cells from the cerebral cortex and crosses through a BBB in vitro model. CONCLUSIONS: Our data showed how BDC-Hfn could improve the stability of BDC. Significant differences in genes associated with inflammation between the same patients before and after BDC-Hfn treatment have been found. Inflammatory genes that are upregulated between AD and CTR after BDC-HFn treatment are converted and downregulated, suggesting a possible therapeutic approach.

Antibodies to neuronal surface antigens in patients with a clinical diagnosis of neurodegenerative disorder.

OBJECTIVES: Autoimmune encephalitis due to antibodies against neuronal surface antigens (NSA-Ab) frequently presents with cognitive impairment, often as the first and prevalent manifestation, but few studies have systematically assessed the frequency of NSA-Ab in consecutive patients with established neurodegenerative disorders. METHODS: We studied sera of 93 patients (41F, 52 M), aged 69.2 ± 9.4 years, with neurodegenerative conditions, and of 50 population controls aged over 60 years. Specific NSA-Abs were investigated by antigen-specific cell-based assays (CBAs). After testing, we evaluated the association between the NSA-Abs and clinical, CSF and radiological features. RESULTS: The patients included 13/93 (13.8%) who had specific antibodies to neuronal surface antigens: 6 GlyR, 3 GABAAR (1 also positive for AMPAR), 2 LGI1, 1 CASPR2 and 1 GABABR. One of the 50 controls (2%) was positive for NMDAR antibody and the others were negative on all tests (P = 0.020). No difference was observed in antibody frequency between patients presenting with parkinsonism and those presenting with dementia (P = 0.55); however, NSA-Ab were more frequent in those with unclassified forms of dementia (5/13, 38.5%) than in those with unclassified parkinsonism (2/9, 22.2%) or with classified forms of dementia (4/43, 9.3%) or parkinsonism (2/28, 7.1%) (P = 0.03). A logistic regression analysis demonstrated that an unclassified diagnosis (P = 0.02) and an irregular progression (P = 0.024) were predictors of seropositive status. CONCLUSIONS: NSA-Abs are relatively frequent in patients with neurodegenerative disorders, particularly in those with an irregular disease progression of atypical clinical features, inconsistent with a recognized diagnosis. The significance of these antibodies and their possible primary or secondary roles need to be investigated in prospective studies.

Effects of Oral Administration of Alprazolam and Lorazepam as Hypnotics on Cardiovascular Parameters in Hypertensive Patients.

BACKGROUND: Previous studies have suggested that evening intake of benzodiazepine affects blood pressure (BP) and/or heart rate (HR) in healthy and hypertensive subjects. The aim of this study was to compare the effect of chronic oral administration of alprazolam and lorazepam as hypnotics on ambulatory BP and HR in patients with mild hypertension. METHODS: Consecutive outpatients of both sexes with newly diagnosed, never-treated mild hypertension were randomized, after a 4-week placebo run-in period, to receive alprazolam 0.5 mg plus placebo, lorazepam 1 mg plus placebo, or placebo plus placebo for 2 weeks in 3 crossover periods, each separated by a 1-week placebo wash-out period. At the end of the initial placebo run-in and of each treatment period, 24-hour ambulatory BP and HR monitoring was performed using a noninvasive device. RESULTS: In the 32 patients, no treatment had any effect on 24-hour and daytime systolic BP (SBP), diastolic BP (DBP), and HR, which remained unchanged. During the nighttime, SBP and DBP values were unaffected by alprazolam, as compared with placebo, whereas DBP was significantly higher after treatment with lorazepam (+3.7%, P < 0.05 vs placebo). Nocturnal HR mean values were significantly increased by lorazepam (+10.1%, P < 0.01 vs placebo), whereas they did not change after alprazolam. CONCLUSIONS: In patients with mild hypertension, oral intake of alprazolam or lorazepam as hypnotics did not affect ambulatory BP or HR values. A slight increase in nighttime DBP was observed with lorazepam, whereas alprazolam showed no effect on nocturnal BP and HR, probably reflecting a stimulating effect of the drug on central α2-receptors.

COVID-19 in patients with myasthenia gravis: Epidemiology and disease course.

INTRODUCTION/AIMS: Coronavirus disease 2019 (COVID-19), a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, has become a global pandemic. Patients with myasthenia gravis (MG), often treated with immunosuppressants, might be at higher risk of developing COVID-19 and of demonstrating a severe disease course. We aimed to study prevalence and describe features of COVID-19 in MG patients. METHODS: In May 2020, we conducted telephonic interviews with MG patients followed at our referral center. We collected structured data regarding MG and COVID-19, which was diagnosed as probable or confirmed according to the European Centre for Disease Prevention and Control case definition. We compared confirmed-COVID-19 prevalence calculated from the beginning of the pandemic in MG patients with that of the overall Pavia district. RESULTS: We interviewed 162 MG patients (median age, 66 y; interquartile range 41-77; males 59.9%), 88 from the Pavia district. Three patients had SARS-CoV-2-confirmed by polymerase chain reaction and eight had probable-COVID-19. In the Pavia district, the prevalence of confirmed-COVID-19 among MG patients (1/88, 1.14%) and overall population (4777/546 515, 0.87%) did not differ (P = .538). Higher Myasthenia Gravis Foundation of America clinicalclass and the need for recent rescue treatment, but not ongoing immunosuppressive treatments, were associated with COVID-19 risk. Of 11 MG patients with probable/confirmed-COVID-19, 3 required ventilator support, and 2 elderly patients died of COVID-19 respiratory insufficiency. Only 1 of11 patients experienced worsening MG symptoms, which improved after increasing their steroid dose. DISCUSSION: The risk of COVID-19 in MG patients seems to be no higher than that of the general population, regardless of immunosuppressive therapies. In our cohort, COVID-19 barely affected MG course.

PSEN1 Compound Heterozygous Mutations Associated with Cerebral Amyloid Angiopathy and Cognitive Decline Phenotype.

Cerebral amyloid angiopathy (CAA) is a cerebrovascular disorder caused by the deposition of amyloid beta-peptide (Aß) aggregates. Aß aggregates lead to vessel rupture and intracerebral hemorrhages, detected by magnetic resonance imaging (MRI). Presenile CAA is usually genetically determined by mutations in the amyloid precursor protein (APP) gene. However, mutations after codon 200 in the presenilin 1 (PSEN1) gene have been reported to facilitate CAA onset. Here, we analyzed the genetic bases in a patient of 55 years old affected by CAA and cognitive decline. DNA was isolated and genetic analysis was performed by Next-Generation Sequencing (NGS). RNA was extracted and retro-transcribed to perform segregation analysis by TOPO-TA cloning. WB analysis was carried out to check the impact of the mutations on protein. Two compound heterozygous mutations in PSEN1 exon 10, such as a novel stop-gain mutation (c.1070C > G) and a pathogenic splice variant (c.1129A > T), were found by NGS. Both mutations altered the presenilin 1 protein, truncating its C-terminal portion. This is the first case of CAA and cognitive decline caused by two compound mutations in PSEN1. With this report, we suggest extending the genetic analysis to PSEN1 when cerebral microbleeds are observed by MRI investigation in a patient affected by presenile cognitive decline.

Different miRNA Profiles in Plasma Derived Small and Large Extracellular Vesicles from Patients with Neurodegenerative Diseases.

Identifying biomarkers is essential for early diagnosis of neurodegenerative diseases (NDs). Large (LEVs) and small extracellular vesicles (SEVs) are extracellular vesicles (EVs) of different sizes and biological functions transported in blood and they may be valid biomarkers for NDs. The aim of our study was to investigate common and different miRNA signatures in plasma derived LEVs and SEVs of Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic Lateral Sclerosis (ALS) and Fronto-Temporal Dementia (FTD) patients. LEVs and SEVs were isolated from plasma of patients and healthy volunteers (CTR) by filtration and differential centrifugation and RNA was extracted. Small RNAs libraries were carried out by Next Generation Sequencing (NGS). MiRNAs discriminate all NDs diseases from CTRs and they can provide a signature for each NDs. Common enriched pathways for SEVs were instead linked to ubiquitin mediated proteolysis and Toll-like receptor signaling pathways and for LEVs to neurotrophin signaling and Glycosphingolipid biosynthesis pathway. LEVs and SEVs are involved in different pathways and this might give a specificity to their role in the spreading of the disease. The study of common and different miRNAs transported by LEVs and SEVs can be of great interest for biomarker discovery and for pathogenesis studies in neurodegeneration.

Familial hemiplegic migraine type 2 due to a novel missense mutation in ATP1A2.

BACKGROUND: The mechanisms of genotype-phenotype interaction in Familiar Hemiplegic migraine type 2 (FHM2) are still far from clear. Different ATP1A2 mutations have been described, with a spectrum of phenotypes ranging from mild to severe. No genotype-phenotype correlations have been attempted. CASE PRESENTATION: We describe an Italian family with FHM and a missense ATP1A2 variant (L425H) not previously described. The clinical picture was mild in all the affected members. CONCLUSIONS: Co-segregation of the variant with the aura phenotype was complete in this family, suggesting a 100% penetrance. In silico protein prediction softwares indicate that this variant may change the 3D structure of ATPA1A2 at the cytoplasmic loop between the two central transmembrane helices. Milder FHM phenotypes are rarely reported in literature, likely because case reports are biased towards the most severe phenotypes, with milder forms possibly misdiagnosed as sporadic migraine with aura forms (MAs), even with complex auras. Further studies taking into account intra-familiar variability and functional consequences on the channel protein may help clarify genotype-phenotype correlations.

Incremental value of amyloid-PET versus CSF in the diagnosis of Alzheimer's disease.

PURPOSE: To compare the incremental diagnostic value of amyloid-PET and CSF (Aß42, tau, and phospho-tau) in AD diagnosis in patients with mild cognitive impairment (MCI) or mild dementia, in order to improve the definition of diagnostic algorithm. METHODS: Two independent dementia experts provided etiological diagnosis and relative diagnostic confidence in 71 patients on 3 rounds, based on (1) clinical, neuropsychological, and structural MRI information alone; (2) adding one biomarker (CSF amyloid and tau levels or amyloid-PET with a balanced randomized design); and (3) adding the other biomarker. RESULTS: Among patients with a pre-biomarker diagnosis of AD, negative PET induced significantly more diagnostic changes than amyloid-negative CSF at both rounds 2 (CSF 67%, PET 100%, P = 0.028) and 3 (CSF 0%; PET 78%, P < 0.001); PET induced a diagnostic confidence increase significantly higher than CSF on both rounds 2 and 3. CONCLUSIONS: Amyloid-PET should be prioritized over CSF biomarkers in the diagnostic workup of patients investigated for suspected AD, as it provides greater changes in diagnosis and diagnostic confidence. TRIAL REGISTRATION: EudraCT no.: 2014-005389-31.

Alzheimer's, Parkinson's Disease and Amyotrophic Lateral Sclerosis Gene Expression Patterns Divergence Reveals Different Grade of RNA Metabolism Involvement.

Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) are neurodegenerative disorders characterized by a progressive degeneration of the central or peripheral nervous systems. A central role of the RNA metabolism has emerged in these diseases, concerning mRNAs processing and non-coding RNAs biogenesis. We aimed to identify possible common grounds or differences in the dysregulated pathways of AD, PD, and ALS. To do so, we performed RNA-seq analysis to investigate the deregulation of both coding and long non-coding RNAs (lncRNAs) in ALS, AD, and PD patients and controls (CTRL) in peripheral blood mononuclear cells (PBMCs). A total of 293 differentially expressed (DE) lncRNAs and 87 mRNAs were found in ALS patients. In AD patients a total of 23 DE genes emerged, 19 protein coding genes and four lncRNAs. Through Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses, we found common affected pathways and biological processes in ALS and AD. In PD patients only five genes were found to be DE. Our data brought to light the importance of lncRNAs and mRNAs regulation in three principal neurodegenerative disorders, offering starting points for new investigations on deregulated pathogenic mechanisms.

Role of Cerebrospinal Fluid Biomarkers and (18)F-florbetapir PET Imaging in the Diagnosis of Primary Progressive Aphasia: A Retrospective Analysis.

The use of biomarkers has recently supported the association between Alzheimer disease (AD) pathology and the logopenic variant of primary progressive aphasia (PPA). We aim to investigate possible differences in cerebrospinal fluid (CSF) biomarker concentrations in the three PPA variants, and to assess any agreement between CSF biomarkers and (18)F-florbetapir PET. A group of 10 PPA were retrospectively enrolled. Patients with logopenic variant (lvPPA) showed different levels of Aß1-42 and p-tau compared to nonfluent/agrammatic and semantic variants (nfv/svPPA). All nfv/svPPA patients had negative amyloid PET. Among the lvPPA group, a negative amyloid PET was found only in one patient, who was also the only one to display a normal CSF. Thus, this small cohort appeared to display an excellent agreement between CSF and (18)F-florbetapir PET and suggest that these examinations may have the same validity in detecting in vivo evidence of AD pathology in PPA clinical variants.

Effect of Evening Bromazepam Administration on Blood Pressure and Heart Rate in Mild Hypertensive Patients.

AIM: To assess the effects of chronic evening oral administration of bromazepam alone or in combination with propranolol on ambulatory blood pressure (BP) and heart rate (HR) in mild hypertensive subjects. METHODS: Thirty-seven mild hypertensive patients after a 2-week placebo period were randomized to bromazepam 3 mg, propranolol 40 mg, bromazepam 3 mg plus propranolol 40 mg or placebo for 2 weeks according to a double-blind, double dummy, cross-over design. After each treatment period, 24-h BP and HR ambulatory monitoring was performed by using a non-invasive device. RESULTS: Ambulatory monitoring showed that during night-time SBP and DBP values were unaffected by bromazepam as compared to placebo, whereas SBP was significantly reduced by propranolol both when taken alone and in combination with bromazepam. HR nocturnal values were significantly reduced by propranolol, whereas they were significantly increased by bromazepan both when taken alone (+11.5%, p < 0.05 vs. placebo) and in combination with propranolol (+12.8%, p < 0.05 vs. propranolol). No significant difference in day-time values of SBP, DBP and HR was observed among the 4 treatment groups. CONCLUSIONS: In mild hypertensive patients, evening consumption of bromazepam for a 2-week period did not affect BP, while it increased nocturnal HR. Such an increase was observed both when bromazepam was taken alone and in combination with propranolol, which suggests that it depends on a bromazepam mediated decrease in vagal tone. Whatever the mechanism, the HR nocturnal increase might be of clinical relevance, due to the role of high HR as cardiovascular risk factor, particularly in already at risk hypertensive subjects.

Diazepam as an oral hypnotic increases nocturnal blood pressure in the elderly.

BACKGROUND: No study has evaluated the cardiovascular effects of diazepam in elderly subjects that assume diazepam to induce sleep. PURPOSE: The present study was carried out in order to evaluate the effects of chronic administration of diazepam as hypnotic drug on blood pressure (BP) and heart rate (HR) in healthy elderly subjects. PATIENTS AND METHODS: Healthy, elderly subjects, aged 65-74 years, were treated with diazepam 5 mg or placebo-both administered once a day in the evening-for 4 weeks in two cross-over periods, each separated by a 2-week placebo period, according to a randomized, double-blind, cross-over design. At the end of each study period, clinical as well as 24-h ambulatory BP and HR were evaluated. RESULTS: A total of 25 subjects were included in the analysis. At the end of a 4-week diazepam treatment, clinical as well 24-h BP and HR mean values were not significantly affected. Analysis of sub-periods showed that during night-time, systolic BP (SBP) values under diazepam were 7.6% higher than under placebo, with a mean difference of 7.9 mmHg (p < 0.01), diastolic BP (DBP) values were 5.8% higher, with a mean difference of 3.7 mmHg (p < 0.05 vs placebo) and HR values were 6.6% higher with a mean difference of 4.2 b/min (p < 0.05). The HR increase observed with diazepam persisted during the morning hours, whereas during the afternoon and evening hours SBP, DBP and HR values were similar in the two treatment groups. CONCLUSIONS: In elderly subjects chronic assumption of diazepam as hypnotic agent produced an increase in BP, in particular SBP, during night-time and of HR during night-time and morning hours. These effects, which probably depend on a diazepam-mediated increase in sympathetic drive and decrease in vagal tone, might be of clinical relevance due to the role of increased BP and HR as independent predictors of cardiovascular morbidity and mortality.

Effect of flunitrazepam as an oral hypnotic on 24-hour blood pressure in healthy volunteers.

PURPOSE: The present study was carried out in order to assess the effects of chronic administration of flunitrazepam (as an oral hypnotic) on 24-h blood pressure (BP) and heart rate (HR) in healthy young adults. MATERIALS AND METHODS: Following a 2-week placebo run-in period, 28 healthy volunteers (13 males and 15 females) between 21 and 30 years were randomized to receive either flunitrazepam 1 mg or placebo (both administered once a day in the evening) for 4 weeks in two cross-over periods; each separated by a 2-week placebo period. At the end of each study period, non-invasive 24-h BP and HR ambulatory monitoring was performed. RESULTS: Flunitrazepam produced a significant decrease in nighttime systolic blood pressure (SBP) (- 6.4 mmHg) and diastolic blood pressure (DBP) (- 4.1 mmHg) (both P < 0.05 vs placebo) without affecting nocturnal HR. During the morning hours, significantly higher values of SBP (+ 7.4 mmHg, P < 0.01), DBP (+ 3.4 mmHg, P < 0.05) and HR (+ 3.9 beats/min, P < 0.05) were observed in the flunitrazepam group compared to the placebo-treated group. No significant differences were noted between the two groups during afternoon and evening hours. CONCLUSIONS: These results suggest that chronic oral administration of 1 mg flunitrazepam as a hypnotic agent causes a significant nocturnal fall in BP and a transient rebound increase of both BP and HR at awakening in the morning. Mechanisms underlying these cardiovascular effects remain unclear, although the direct vasodilatory effect, which is typical of flunitrazepam (with consequent reflex counter-regulatory responses), and the attenuation of baroreflex sensitivity are likely to play a major role.

Effect of Diazepam on 24-Hour Blood Pressure and Heart Rate in Healthy Young Volunteers.

AIM: To assess the effects of evening chronic administration of diazepam on 24-h blood pressure (BP) and heart rate (HR) in healthy young adults. METHODS: This randomized double blind, cross-over study evaluated the effects of diazepam 5 mg or placebo, both ingested in the evening, on 24-h ambulatory BP and HR in healthy subjects aged 21-30. RESULTS: A total of 30 subjects were included in the analysis. At the end of 4-week diazepam intake, an increase in 24-h HR mean values was found (+5.2 beats/min, p < 0.05). Analysis of subperiods showed that diazepam produced a 10.1% increase in night-time HR (+6.1 beats/min, p < 0.01) without affecting BP. A significant HR rise (+4.9 beats/min, p < 0.05) and SBP reduction (-3.8 mm Hg, p < 0.05) were observed in the morning hours. The HR increase persisted in day-time hours (+4.6 beats/min, p < 0.05), while BP values resulted unaffected. CONCLUSIONS: In healthy subjects, diazepam taken as a hypnotic agent induces a significant HR increase, possibly mediated by a decrease in vagal tone. This effect might be of clinical relevance due to the role that HR plays as an independent cardiovascular risk factor.

Ambulatory 24-h ECG monitoring and cardiovascular autonomic assessment for the screening of silent myocardial ischemia in elderly type 2 diabetic hypertensive patients.

The aim of the study was to evaluate the usefulness of Holter monitoring for the detection of silent myocardial ischemia (SMI) in elderly type 2 diabetic patients with hypertension and the possible relationship between SMI and cardiovascular autonomic neuropathy (CAN). Two hundred and forty-three asymptomatic outpatients, aged 65-75 years, with type 2 diabetes and essential hypertension underwent 24-h ECG monitoring and 5 tests for the evaluation of both parasympathetic (heart rate variability, response to breath deeping, and Valsalva manoeuvre) and sympathetic (cold pressor test and orthostatic hypotension test) autonomic function. A total of 518 asymptomatic episodes of ST depression during Holter monitoring indicative of SMI were detected in 51 of the 243 studied patients (20.9 %). None of the patients with ST depression episodes exhibited a normal response to at least one of the evaluated autonomic function tests, whereas 22 of the 192 patients without ST changes (11.4 %) exhibited a normal response to all tests. Abnormality in both parasympathetic and sympathetic function test responses was found in 94.1 % of patients with ST depression episodes vs 26.1 % of those without ST changes (P < 0.001). Statistical evaluation of the relationship between the abnormal response to single autonomic function test and episodes of ST depression was highly significant for all the 5 tests (P < 0.001). These results indicate that: (a) Holter monitoring enables to detect ST segment changes indicative of SMI in 20.9 % of elderly diabetic patients with hypertension; (b) the presence of autonomic cardiac dysfunction in these patients suggests a role of diabetic neuropathy in the pathogenesis of SMI; and

Twenty-four-hour blood pressure profile, orthostatic hypotension, and cardiac dysautonomia in elderly type 2 diabetic hypertensive patients.

PURPOSE: The aim of this study was to evaluate the relationship between orthostatic hypotension (OH), defined as a decrease in systolic blood pressure (SBP) ≥20 mmHg and/or a decrease in diastolic blood pressure (DBP) ≥10 mmHg, and 24-h ambulatory BP profile in elderly hypertensive type 2 diabetic patients. METHODS: After a 2-week antihypertensive wash-out period, 200 hypertensive well-controlled diabetic outpatients, aged 65-75 years, underwent a clinical examination, including BP measurements, ECG, 24-h ABP monitoring (ABPM), an orthostatic test, and three tests for cardiovascular autonomic function assessment [deep breathing, heart rate (HR) variability, resting HR]. RESULTS: According to their nighttime BP profile, patients were divided into three groups: dippers (n = 86) (BP fall during nighttime ≥10 %), non-dippers (n = 80) (BP fall during nighttime 0-10 %), and reverse dippers (n = 34) (nighttime BP > daytime BP). Orthostatic test produced a significantly greater orthostatic SBP fall in dippers and even more in reverse dippers. In these latter, a significant fall was observed also in DBP. Prevalence of OH was 9.3 % in dippers, 30 % in non-dippers, and 79.4 % in reverse dippers. CONCLUSIONS: In elderly hypertensive type 2 diabetics, a blunted nocturnal BP fall is associated with OH and autonomic dysfunction. These data suggest that ABPM should be performed in the assessment of hypertensive diabetic patients in whom the cardiovascular dysautonomia is suspected or the signs of it are present (such as OH).