Can We Slow Down Biological Age Progression? Study Protocol for the proBNPage Reduction (PBAR) Randomized, Double-Blind, Placebo-Controlled Trial (Effects of 4 "Anti-Aging" Food Supplements in Healthy Older Adults).

Purpose: The availability of a simple and reliable marker of biological age might allow an acceleration of the research in the field of longevity extension. Previous studies suggest that this marker might be the N-terminal of B-type natriuretic peptide precursor (NT-proBNP), from which proBNPage, a biological age surrogate, can be calculated. Objectives of the study: 1) To fine-tune the method of proBNPage progression assessment and 2) To establish whether 4 "anti-aging" treatments, which provided promising results in previous studies, can modify proBNPage progression. Patients and Methods: This is a double-blind randomized placebo-controlled clinical trial on 120 adults aged 65-80 years, free of cardiovascular diseases. Participants will be randomized into 3 groups: A) Coenzyme Q10 100 mg bid + Selenium 100 mcg; B) Resveratrol 350 mg bid + TA-65 (Astragalus Membranaceus extract) 100U; C) Placebo-1 bid + Placebo-2. They will be followed for 2 years and checked 8 times, to assess both proBNPage progression and treatment safety. Secondary variables (handgrip strength, aerobic capacity at the step test and quality of life) will also be assessed. Primary outcome will be the demonstration of significant changes of proBNPage, compared to baseline, in the 3 groups at 6, 12, 18 and 24 months. Secondary outcome will be the demonstration of similar changes of secondary variables. Statistical analyses will be mainly performed by repeated measures ANOVA (both according to intention to treat and per protocol) and paired t tests. The study was approved by the Ethics Committee Area Vasta Emilia Centro, Emilia-Romagna Region, ID: 64/2022/Sper/AOUBo. Trial registration: ClinicalTrials.gov, NCT05500742. Conclusion: The use of proBNPage as a surrogate of biological age may prove an easy method to select anti-aging treatments worthy of further, more complex assessments.

Probability of Cardioembolic vs. Atherothrombotic Pathogenesis of Cryptogenic Strokes in Older Patients.

Some clinical, laboratory, ECG, and echocardiographic parameters could provide useful indications to assess the probability of cardioembolism or atherothrombosis in cryptogenic strokes. We retrospectively examined 290 patients with ischemic stroke aged ≥60 years, divided into 3 groups: strokes originating from large artery atherothrombosis (n = 92), cardioembolic strokes caused by paroxysmal atrial fibrillation (n = 88) and cryptogenic strokes (n = 110). In addition to echocardiographic and routine clinical-laboratory variables, neutrophil:lymphocyte ratio, red blood cell distribution width, mean platelet volume, P wave and PR interval duration and biphasic inferior P waves, both on admission and after 7 to 10 days, were also considered. By multiple logistic regression, cardioembolic strokes were compared with large artery atherothrombosis strokes, and beta coefficients were rounded to produce a scoring system. Late PR interval ≥188 ms, left atrium ≥4 cm, left ventricular end-diastolic volume <65 ml, and posterior circulation syndrome were associated with paroxysmal atrial fibrillation (positive scores). In contrast, male gender, hypercholesterolemia, and initial platelet count ≥290 × 109/L were associated with atherothrombosis of large arteries (negative scores). The algebraic sum of these scores produced values indicative of cardioembolism if >0 (positive predictive value 89.1%), or of atherothrombosis, if ≤0 (positive predictive value 72.5%). The area under the receiver operating characteristic curve was 0.85. Among cryptogenic strokes, 41.5% had a score >0 (probable atrial fibrillation) and 58.5% had a score ≤0 (possible atherothrombosis). In conclusion, a scoring system based on electrocardiogram, laboratory, clinical and echocardiographic parameters can provide useful guidance for further investigations and secondary prevention in older patients with cryptogenic stroke.

Predicting Failure to Recover Swallowing in Patients with Severe Post-stroke Dysphagia: The DIsPHAGIc Score.

In post-stroke dysphagia, early identification of patients at highest risk of failing swallowing recovery (SR) would be useful to decide which of them should undergo percutaneous endoscopic gastrostomy. The studies on this subject were numerous but generally based on small statistical samples. In this retrospective study, 1232 patients with ischemic or hemorrhagic stroke (73.7 ± 13.0 years, 51% men) were assessed: 593 non-dysphagic, 351 partially dysphagic and 288 totally dysphagic. Among the latter, 45.1% could not recover oral intake. A score to assess the risk of failing SR was obtained from the group with total dysphagia, and further 210 patients with total post-stroke dysphagia were utilized for validation. A regular progression of stroke severity markers, complications and mortality was observed from non-dysphagic, to partially dysphagic, up to totally dysphagic patients. Among the latter, seven variables were independently associated with failure of SR, and formed the "DIsPHAGIc score": cerebral lesion Diameter ≥ 6 cm (+ 1), left frontal Ischemia (- 1), Partial anterior circulation syndrome (- 1), Hypoxia (+ 1), Antiplatelet drug (+ 1), GCS verbal reaction < 4 (+ 1), Internal capsule ischemia (- 1). The area under the ROC curve was 0.79 (95% CI 0.74-0.85). For total scores ≥ 2 there was a high risk of failing SR, with specificity 76.9%, sensitivity 72.1% and accuracy 74.7%. The application of the DIsPHAGIc score to the validation sample provided almost identical results. The evolution of post-stroke dysphagia towards irreversibility can be predicted by a simple, reproducible and robust scoring system based on 7 variables commonly available during hospitalization.

Prognostic significance of diabetes and stress hyperglycemia in acute stroke patients.

BACKGROUND: Hyperglycemic non-diabetic stroke patients have a worse prognosis than both normoglycemic and diabetic patients. Aim of this study was to assess whether hyperglycemia is an aggravating factor or just an epiphenomenon of most severe strokes. METHODS: In this retrospective study, 1219 ischemic or hemorrhagic stroke patients (73.7 ± 13.1 years) were divided into 4 groups: 0 = non-hyperglycemic non-diabetic, 1 = hyperglycemic non-diabetic, 2 = non-hyperglycemic diabetic and 3 = hyperglycemic diabetic. Hyperglycemia was defined as fasting blood glucose ≥ 126 mg/dl (≥ 7 mmol/l) measured the morning after admission, while the diagnosis of diabetes was based on a history of diabetes mellitus or on a glycated hemoglobin ≥ 6.5% (≥ 48 mmol/mol), independently of blood glucose levels. All diabetic patients, except 3, had Type 2 diabetes. The 4 groups were compared according to clinical history, stroke severity indicators, acute phase markers and main short term stroke outcomes (modified Rankin scale ≥ 3, death, cerebral edema, hemorrhagic transformation of ischemic lesions, fever, oxygen administration, pneumonia, sepsis, urinary infection and heart failure). RESULTS: Group 1 patients had more severe strokes, with larger cerebral lesions and higher inflammatory markers, compared to the other groups. They also had a high prevalence of atrial fibrillation, prediabetes, previous stroke and previous arterial revascularizations. In this group, the highest frequencies of cerebral edema, hemorrhagic transformation, pneumonia and oxygen administration were obtained. The prevalence of dependency at discharge and in-hospital mortality were equally high in Group 1 and Group 3. However, in multivariate analyses including stroke severity, cerebral lesion diameter, leukocytes and C-reactive protein, Group 1 was only independently associated with hemorrhagic transformation (OR 2.01, 95% CI 0.99-4.07), while Group 3 was independently associated with mortality (OR 2.19, 95% CI 1.32-3.64) and disability (OR 1.70, 95% CI 1.01-2.88). CONCLUSIONS: Hyperglycemic non-diabetic stroke patients had a worse prognosis than non-hyperglycemic or diabetic patients, but this group was not independently associated with mortality or disability when size, severity and inflammatory component of the stroke were accounted for.

Association of Left Ventricular Hypertrophy and Atrial Fibrillation with Hemorrhagic Evolution of Small Vessel Disease.

OBJECTIVES: Cerebral small vessel disease (SVD) is often associated with hypertension and may evolve towards intracerebral hemorrhage (ICH) or lacunar ischemic stroke. However, the factors favoring the evolution towards ICH or lacunar stroke are not well understood. MATERIALS AND METHODS: This retrospective study included 326 consecutive patients (71.1±13.2 years, 38% women): 143 with deep ICH and 183 with lacunar lesions (LL) <2 cm, which were visible in a deep location on brain CT scan. Among LL patients, 143 had a small-artery occlusion (SAO) stroke according to the TOAST classification. Clinical characteristics plus laboratory and neuroradiological variables of these patients had been prospectively collected and a subgroup underwent echocardiography. RESULTS: In multivariate analysis, ICH patients (97% hypertensive), compared to SAO patients (89% hypertensive), had greater left ventricular wall thickness (LVWT; OR 4.15, 95%CI 1.64-10.53, for those with LVWT ≥ 1.4 cm, 70% of whom were hemorrhagic) and lower prevalence of white matter lesions (OR 0.30, 95%CI 0.13-0.70), ever smokers (OR 0.39, 95%CI 0.18-0.82) and diabetics (OR 0.29, 95% CI 0.10-0.84). Moreover, ICH patients had a greater prevalence of atrial fibrillation than LL patients (OR 3.14, 95%CI 1.11-8.93), and so they were more often anticoagulated. CONCLUSIONS: Most SVD patients were hypertensive, but those evolving towards ICH were characterized by organ damage at the cardiac level (increase in LVWT and atrial fibrillation), while those evolving towards lacunar stroke were characterized by a higher prevalence of smokers and diabetics, and by organ damage at the cerebral level (white matter lesions).

The association of proBNPage with manifestations of age-related cardiovascular, physical, and psychological impairment in community-dwelling older adults.

NT-proB-type natriuretic peptide (NT-proBNP) serum concentration can be transformed by simple formulas into proBNPage, a surrogate of biological age strongly associated with chronological age, all-cause mortality, and disease count. This cross-sectional study aimed to assess whether proBNPage is also associated with other manifestations of the aging process in comparison with other variables. The study included 1117 noninstitutionalized older adults (73.1 ± 5.6 years, 537 men). Baseline measurements of serum NT-proBNP, erythrocyte sedimentation rate, hemoglobin, lymphocytes, and creatinine, which have previously been shown to be highly associated with both age and all-cause mortality, were performed. These variables were compared between subjects with and without manifestations of cardiovascular impairment (myocardial infarction (MI), stroke, peripheral artery disease (PAD), arterial revascularizations (AR)), physical impairment (long step test duration (LSTD), walking problems, falls, deficit in one or more activities of daily living), and psychological impairment (poor self-rating of health (PSRH), anxiety/depression, Mini Mental State Examination (MMSE) score < 24). ProBNPage (years) was independently associated (OR, 95% CI) with MI (1.08, 1.07-1.10), stroke (1.02, 1.00-1.05), PAD (1.04, 1.01-1.06), AR (1.06, 1.04-1.08), LSTD (1.03, 1.02-1.04), walking problems (1.02, 1.01-1.03), and PSRH (1.02, 1.01-1.02). For 5 of these 7 associations, the relationship was stronger than that of chronological age. In addition, proBNPage was univariately associated with MMSE score < 24, anxiety/depression, and falls. None of the other variables provided comparable performances. Thus, in addition to the known associations with mortality and disease count, proBNPage is also associated with cardiovascular manifestations as well as noncardiovascular manifestations of the aging process.

"2-step MCI-AD": a simple scoring system to predict rapid conversion from mild cognitive impairment to Alzheimer dementia.

BACKGROUND: Several techniques are available to identify, among patients with mild cognitive impairment (MCI), those at risk of conversion to Alzheimer dementia (CAD). However, simple cost-effective methods to assess the risk are not available yet. METHODS: This retrospective study included 143 MCI outpatients (76.6±5.2 years, 46.8% women). Baseline variables were common neuropsychological tests (including Mini Mental State Examination-MMSE and Montreal Cognitive Assessment-MoCA), brain CT and 18F-fluorodeoxyglucose (FDG)-PET. Outcome variable was CAD after 1 year. RESULTS: At follow-up, 31 (21.7%) patients had CAD. In multivariable analysis (OR, 95% CI), female sex (4.7, 1.6-14.0), MoCA-executive component <3 (6.3, 2.1-19.2), left medial temporal atrophy (MTA) ≥3 (5.4, 1.9-15.7) and FDG-PET suggesting CAD (5.4, 1.9-15.7) were associated with CAD (area under ROC curve 0.873). Without FDG-PET, MMSE score <28 remained associated with CAD (6.0, 2.2-16.9). As first step (before FDG-PET execution), we counted 1 point for MMSE <28, executive MoCA <3 and left MTA ≥3. With 2-3 points CAD probability was high (75%) and with 0 points it was low (6.5%). Thus, FDG-PET (second step) might be performed only in patients with 1 point (probability 19.7%, 42.7% of patients). Among them, 35% had a positive FDG-PET, suggesting high risk. Overall, 28.0% of patients were considered at high risk (specificity 83.9%, sensitivity 71.0%, accuracy 81.1%). CONCLUSION: With a 2-step procedure, less than half of MCI patients might undergo FDG-PET and nearly a quarter of our patients was found to be at high CAD risk, including almost three quarters of future CADs.

Carotid Endarterectomy is often not Possible after an Unheralded Stroke: Unheralded Stroke in Carotid Artery Stenosis.

OBJECTIVES: The ongoing literature recommends carotid endarterectomy (CEA) primarily for patients with neurological symptoms, however CEA can be precluded by the onset of a severe stroke or a total carotid occlusion. The present study aims to evaluate the effect of unheralded strokes in patients with a previously asymptomatic carotid stenosis (ACS) possibly considered for CEA. MATERIALS AND METHODS: From 2009 to 2019, patients with an unheralded stroke from an ACS were considered. By neurological examination, patients were divided in unfit-for-CEA (uCEA) - either for the severity of the stroke (according to modified Rankin-Scale - mRS) or the onset of a total carotid occlusion - and patients submitted to CEA. Predictors for uCEA and stroke severity were evaluated. RESULTS: Over a total of 532 patients with symptomatic carotid stenosis, 277 (52%) with unheralded stroke were included in the study. One hundred and one (36%) were considered uCEA: 64(23%) due to their neurological conditions (mRS:5) and 37 (13%) because of the onset of carotid occlusion. One hundred seventy-six (64%) patients underwent CEA. The preoperative medical therapy was similar in uCEA vs CEA patients. Age≥80 years and female sex were independently associated with uCEA (OR:5.9, 95%CI:3.1-11.4, P<.01; OR:3.9, 95%CI:2.0-7.6, P<.01. respectively). Patients submitted to CEA had mRS: 0-2 in 102(37%) cases and mRS:3-4 in 74 (27%). The contralateral carotid occlusion (CCO) was independently associated with mRS:3-4 (OR:8.4, 95%CI 1.8-79, P=.01). Postoperative stroke rate after CEA was 2.9% (4/167); patients with preoperative mRS:3-4 had a higher risk for postoperative stroke compared to those with mRS:0-2 (5.9% vs. 0%. P=.02). CONCLUSIONS: An unheralded stroke in patients with ACS leads to a severe neurological damage in more than half of cases, either precluding CEA (36%) or increasing the risk of postoperative complications (27%). Female sex, age≥80 and CCO are independent predictors of these occurrences and should be considered in ACS patients.

N-terminal pro B-type natriuretic peptide (NT-proBNP): a possible surrogate of biological age in the elderly people.

NT-proB-type natriuretic peptide (NT-proBNP) increases with age and is associated with all-cause mortality. With this study, we assessed its possible utilization as a marker of biological age in comparison with other variables. The study included 1079 non-institutionalized elderly subjects (mean age 72.8 ± 5.5 years, 561 women). Baseline measurements were performed of serum NT-proBNP and of some laboratory variables previously utilized to estimate biological age (creatinine, albumin, C-reactive protein, cholesterol, blood glucose, leukocytes, lymphocytes, hemoglobin, mean cell volume). During 7 years of follow-up, 114 all-cause deaths occurred. The logarithm of NT-proBNP was the most age-related parameter (r = 0.35, P < 0.0001). Its relationship with mortality, according to Cox regression and ROC curve (AUC = 0.707, 95% CI 0.654-0.759), was stronger than that of all other variables, including age. In multivariate analysis, only NT-proBNP and age remained independently associated with mortality. The regression lines between age and NT-proBNP (pg/ml) allowed a separate estimation of biological age ("proBNPage") for men (= [log(NT-proBNP) + 1.2068]/0.0827) and for women (= [log(NT-proBNP) - 1.5258]/0.0478). The hazard ratio of all-cause mortality for the fifth quintile of proBNP age (≥ 85 years) compared with the first quintile (< 61 years) was 7.9 (95% CI 3.6-17.5). Similarly, the difference between pro-BNPage and chronological age was associated with a hazard ratio of 3.5 in the fifth quintile (95% CI 1.9-6.4) and was associated with disease count (P for trend = 0.0002). In conclusion, NT-proBNP was the best indicator of biological age, which can be estimated by simple formulas and might be used for prognostic purposes or as a surrogate end point in epidemiological and intervention studies.

Venous thromboembolism prevention with low molecular weight heparin may reduce hemorrhagic transformation in acute ischemic stroke.

BACKGROUND: Subcutaneous heparin at a prophylactic dose (SHPD) is a rather common treatment in ischemic stroke, but whether it confers an increased risk of hemorrhagic transformation of cerebral infarct (HT) and whether its reduction or discontinuation favors HT regression are presently poorly understood. METHODS: Two samples of ischemic stroke patients with a cerebral lesion diameter ≥ 3 cm on brain CT scan, admitted over 7 years to our stroke unit, were retrospectively examined: (1) patients treated or not treated with SHPD (enoxaparin 4000 U/day), with subsequent assessment of possible HT appearance (N = 267, mean age 75.9 ± 12.8 years) and (2) patients treated with SHPD, with HT and subsequent reduction/discontinuation or maintenance of the initial dose, and subsequent assessment of HT evolution (N = 116, mean age 75.7 ± 11.1 years). HT severity was quantified according to the ECASS study (HT score). RESULTS: In the first sample, after adjustment for age, sex, stroke severity, cerebral lesion diameter, and other possible confounders, SHPD was inversely associated with HT appearance (hazard ratio 0.62, 95% CI 0.39-0.98, P = 0.04). In the second sample, after adjustment for age, sex, stroke severity, cerebral lesion diameter, and initial HT severity, SHPD reduction/discontinuation had an inverse effect on both HT score improvement (odds ratio 0.42, 95% CI 0.18-0.99, P = 0.049) and HT improvement according to neuroradiological reports (odds ratio 0.34, 95% CI 0.14-0.82, P = 0.015). CONCLUSIONS: This retrospective study suggests that SHPD may play a protective role in HT appearance and evolution, which requires verification by a randomized clinical trial.

Prognostic value of non-alcoholic fatty liver disease in the elderly patients.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the liver manifestation of metabolic syndrome, a risk factor for mortality and cardiovascular morbidity, but we ignore the role of steatosis per se in survival, and there is very little information about this condition in the geriatric patient. AIMS: With the present study, we investigated the independent prognostic value of NAFLD on overall mortality in the elderly. METHODS: Within the Pianoro Project, involving people ≥ 65 years, anamnestic, clinical and laboratoristic data related to NAFLD, insulin resistance, diabetes/hyperglycemia, hypertension, obesity and dyslipidemia were collected in 804 subjects (403 male, 401 female). These subjects were followed up for mortality for a median time of 12.6 years. A multivariate analysis was performed to evaluate the prognostic value of the covariates. RESULTS: At Kaplan-Meier estimator the presence of NAFLD seems to be associated to a lower mortality, and survival tends to increase with the increasing of steatosis grade. Cox's analysis found that survival is increased for subjects having hypercholesterolemia (RR = 0.565), NAFLD (RR = 0.777), hypertension (RR = 0.711) and in female (RR = 0.741), while it is decreased for the older subjects (RR = 3.046), in patients with hypertriglyceridemia (RR = 1.699) and for diabetics (RR = 1.797). The variables BMI and HDL-cholesterol have no role. CONCLUSION: The data obtained in our study show that NAFLD is not associated to overall mortality in the elderly population.

Usefulness of the ACTEL Score to Predict Atrial Fibrillation in Patients with Cryptogenic Stroke.

INTRODUCTION: To assess the probability of undetected atrial fibrillation (AF) in patients with ischemic stroke, we previously compared patients who were first diagnosed with AF with patients with large or small artery disease and obtained the MrWALLETS 8-item scoring system. In the present study, we utilized cryptogenic strokes (CS) as the control group, as AF is normally sought among CS patients. METHODS: We retrospectively examined 191 ischemic stroke patients (72.5 ± 12.6 years), 68 with first diagnosed AF and 123 with CS, who had undergone 2 brain CT scans, echocardiography, carotid/vertebral ultrasound, continuous electrocardiogram monitoring and anamnestic/laboratory search for cardiovascular risk factors. RESULTS: In logistic regression, 5 variables were independently associated with AF, forming the "ACTEL" score: Age ≥75 years (OR 2.42, 95% CI 1.18-4.96, p = 0.02; +1 point); hyperCholesterolemia (OR 0.38, 95% CI 0.18-0.78, p = 0.009; -1 point); Tricuspid regurgitation ≥ mild-to-moderate (OR 4.99, 95% CI 1.63-15.27, p = 0.005; +1 point); left ventricular End-diastolic volume <65 mL (OR 7.43, 95% CI 2.44-22.6, p = 0.0004; +1 point); Left atrium ≥4 cm (OR 4.57, 95% CI 1.97-10.62, p = 0.0004; +1 point). The algebraic sum of these points may range from -1 to +4. For AF identification, the area under the receiver operating characteristic curve was 0.80 (95% CI 0.73-0.87). With a cutoff of ≥2, positive predictive value was 80.8%, specificity 92.7% and sensitivity 55.9%. CONCLUSIONS: The ACTEL score, a simplified and improved version of the MrWALLETS score, allows the identification of patients with first diagnosed AF, in the context of CSs, with a high positive predictive value.

Predicting hemorrhagic transformation and its timing from maximum cerebral lesion diameter in nonlacunar ischemic strokes.

OBJECTIVES: We performed this retrospective cohort study to establish which factors are mostly indicative of the appearance of hemorrhagic transformation (HT) and of its time course in a sample of nonlacunar ischemic strokes. MATERIALS AND METHODS: In 402 patients with nonlacunar ischemic stroke (75.0 ± 12.7 years, 192 male), clinical, laboratory, and neuroimaging variables obtained during the first 3 days of hospitalization were compared between patients with and without HT at computer tomography scan. RESULTS: HT was documented in 129 patients (32.1%), including 36 with parenchymal hematoma (PH), after a median time of 6 days (range 1-27). Many variables were univariately associated with HT, but only 5 of them were confirmed in Cox regression (Hazard Ratio, 95% Confidence Interval): maximum cerebral lesion diameter (CLD) in cm (1.12, 1.06-1.18; p = .0001), hemoglobin in g/dl (1.16, 1.06-1.27; p = .002), blood glucose in mmol/L (1.10, 1.03-1.18; p = .007), prior anticoagulant therapy (1.82, 1.10-3.03; p = .02), and edema with mass effect (1.72, 1.08-2.75; p = .02). Thus, the most significant predictor was CLD. The overall risk of HT was minimum for CLD < 2 cm (1.5%), intermediate for CLD ≥ 2 and < 5 cm (22%), and maximum for CLD ≥ 5 cm (58%). The residual probability of having HT decreased progressively over time, and a simple formula is proposed to predict, from CLD in cm, when the probability of HT falls below 10%. CONCLUSIONS: The main determinant of HT was CLD, a simple quantitative parameter that could prove useful, in particular, in deciding the timing of anticoagulation in cardioembolic stroke patients.

Predicting cerebral edema in ischemic stroke patients.

OBJECTIVES: To produce a scoring system for predicting the development of edema in ischemic stroke patients without edema on admission. METHODS: This retrospective study included 572 ischemic stroke patients (73.3 ± 13.0 years, 300 male) without signs of cerebral edema on the first CT scan, which was performed on admission. Another scan was normally performed 3 days later, and subsequently whenever needed. Edema was defined as cerebral hypodensity with compression of lateral ventricles. The main clinical, laboratory, and instrumental variables obtained during the first 24 h were related to the appearance of edema on the CT scans performed after the first one. RESULTS: Cerebral edema occurred in 158 patients (27.6%) after a median time of 4 days. The variables independently associated with edema development were (odds ratio, 95% CI) the following: (1) total anterior circulation syndrome (4.20, 2.55-6.93; P < 0.0001), (2) hyperdense appearance of middle cerebral artery (4.12, 2.03-8.36; P = 0.0001), (3) closed eyes (2.53, 1.39-4.60; P = 0.002), (4) vomiting (3.53, 1.45-8.60; P = 0.006), (5) lacunar cerebral syndrome (0.36, 0.17-0.77; P = 0.008); and (6) white matter lesions (0.53, 0.33-0.86; P = 0.01). Counting one positive point for the first four variables and one negative point for the last two variables, a scoring system (E-score) was built. Cerebral edema could be predicted when the score was ≥ 1 (positive predictive value 61.6%, specificity 85.3%, sensitivity 62.0%). The area under the receiver operating characteristic curve was 0.78. CONCLUSIONS: In ischemic stroke patients, six variables obtained during the first 24 h of hospitalization were predictive of subsequent cerebral edema development.

Predictors of cognitive impairment assessed by Mini Mental State Examination in community-dwelling older adults: relevance of the step test.

BACKGROUND: Several predictors of cognitive impairment assessed by Mini Mental State Examination (MMSE) have previously been identified. However, which predictors are the most relevant and what is their effect on MMSE categories remains unclear. METHODS: Cross-sectional and longitudinal study using data from 1116 older adults (72.6 ±â€¯5.6 years, 579 female), 350 of whom were followed for 7 years. At baseline, the following variables were collected: personal data, marital status, occupation, anthropometric measures, risk factors, previous cardiovascular events, self-rated health and physical activity during the last week. Furthermore, routine laboratory tests, abdominal echography and a step test (with measurement of the time needed to ascend and descend two steps 20 times) were performed. The associations of these variables with cross-sectional cognitive deficit (MMSE < 24) and longitudinal cognitive decline (decrease of MMSE score over 7 years of follow-up) were investigated using logistic regression models. RESULTS: Cross-sectional cognitive deficit was independently associated with school education ≤ 5 years, prolonged step test duration, having been blue collar or housewife (P ≤ 0.0001 for all) and, with lower significance, with advanced age, previous stroke and poor recent physical activity (P < 0.05). Longitudinal cognitive decline was mainly associated with step test duration (P = 0.0001) and diastolic blood pressure (P = 0.0002). The MMSE categories mostly associated with step test duration were orientation, attention, calculation and language, while memory appeared to be poorly or not affected. CONCLUSIONS: In our cohort of older adults, step test duration was the most relevant predictor of cognitive impairment.

Inverse Association Between Neck Pain and All-Cause Mortality in Community-Dwelling Older Adults.

Objective: In a previous study, we found an apparent protective effect of neck pain on all-cause mortality in subjects older than age 85 years. The present longitudinal investigation was performed to verify this unexpected finding in a larger sample and to establish its significance. Design: Population follow-up study. Setting: Three towns of Northern Italy. Subjects: We examined 5,253 community-dwelling residents age 65-102 years (55% female). Methods: Through a postal questionnaire, baseline information was obtained concerning cardiovascular risk factors, self-rated health, physical activity, cardiovascular events, medical therapy, and presence of pain in the main joints. Seven-year all-cause mortality was the end point. Results: During follow-up, 1,250 people died. After adjustment for age, sex, anti-inflammatory drugs, physical activity, and main risk factors, neck pain was inversely associated with mortality (hazard ratio = 0.74, 95% confidence interval = 0.64-0.86, P < 0.001). This association was present, with high significance, in each of the eight following subgroups: men, women, age 65-74 years, age 75-84 years, age ≥85 years and residents of each of the three towns. The subjects without neck pain (N = 3,158) were older, more often men, less often hypercholesterolemic, less physically active, and had more frequently had a stroke than the subjects with neck pain (N = 2,095). There were no differences in the causes of death between subjects with or without neck pain. Conclusion: This study has confirmed the existence of an independent inverse association between neck pain and mortality in the elderly, suggesting that reduced sensitivity to neck pain may be a new marker of frailty.

Usefulness of the MrWALLETS Scoring System to Predict First Diagnosed Atrial Fibrillation in Patients With Ischemic Stroke.

Some cryptogenic strokes are caused by undetected paroxysmal atrial fibrillation (AF) and could benefit from oral anticoagulation. In this study, we searched for echocardiographic parameters associated with first diagnosed AF, to form a scoring system for the identification of patients with AF. We examined 571 patients with ischemic stroke (72.7 ± 13.5 years, 50.6% women), subdivided into 4 groups: documented cause without AF, first diagnosed AF, known paroxysmal AF, and permanent AF. All patients underwent transthoracic echocardiography, brain computed tomography scan, carotid/vertebral ultrasound, and continuous electrocardiographic monitoring. Eight factors independently characterized first diagnosed AF and formed the "MrWALLETS" score: mitral regurgitation, mild-to-moderate (+1), white matter lesions (-1), age ≥75 years (+1), left atrium ≥4 cm (+1), cerebral lesion diameter ≥4 cm (+1), left ventricular end-diastolic volume <65 ml (+1), tricuspid regurgitation ≥moderate (+1), carotid stenosis ≥50% (-1). In the patients with ≥3 points, positive predictive value was 80%, specificity 97.5%, and sensitivity 57.1%. In the patients with ≥2 points sensitivity rose to 85.7%, but positive predictive value was 47.1%. The area under the receiver-operating characteristic curve was 0.89 (95% CI 0.83 to 0.95). There were important differences among AF groups, which therefore could not be merged. In conclusion, 4 echocardiographic parameters, 3 additional instrumental parameters, and age allow the identification of stroke patients with first diagnosed AF with high positive predictive value.

Physical Activity and Other Determinants of Survival in the Oldest Adults.

OBJECTIVES: To determine the role of physical activity as a possible survival determinant in the oldest adults. DESIGN: Prospective, longitudinal, population-based cohort. SETTING: The Pianoro Study of community-dwelling older adults in three towns in northern Italy. PARTICIPANTS: Noninstitutionalized individuals aged 85 and older (n = 500; mean age 89.6 ± 3.1, 65% female). MEASUREMENTS: Participants provided information on marital status, educational level, previous work activity, cardiovascular risk factors, previous cardiovascular events, self-rated health, joint pain, and functional status. Physical activity was quantified using the Physical Activity Scale for the Elderly. Seven-year mortality was known for all subjects. RESULTS: During the 7 years of follow-up, 365 subjects died. According to Cox proportional hazards regression, the following factors were found to be independently associated with mortality: PASE score (hazard ratio (HR) = 0.987, 95% confidence interval (CI) = 0.981-0.993, P < .001), male sex (HR = 1.642, 95% CI = 1.411-2.068, P < .001), age in years (HR = 1.077, 95% CI = 1.040-1.116, P < .001), previous stroke (HR = 1.908, 95% CI = 1.362-2.673, P < .001), poor self care (HR = 1.662, 95% CI = 1.231-2.246, P < .001), neck pain (HR = 0.649, 95% CI = 0.497-0.849, P = .002), self rated health (HR = 0.991, 95% CI = 0.985-0.997, P = .002). CONCLUSION: In the oldest adults, accurate quantification of physical activity may provide important prognostic information. The predictive value of cardiovascular risk factors, except age, male sex, and prior stroke, was confirmed to be negligible. An unexpected inverse association between neck pain and mortality may require further investigation.

Prognostic significance of carotid and vertebral ultrasound in ischemic stroke patients.

OBJECTIVES: The ultrasound investigation of carotid and vertebral arteries is routinely performed in stroke patients to determine the etiopathogenetic classification and possible need of revascularization. However, the medium and long-term prognostic implications of carotid and vertebral ultrasound in ischemic stroke patients are not yet known. METHODS: This study included 309 ischemic stroke patients (mean age 76.3; 160 men). They all had undergone carotid and vertebral ultrasound (carotid stenoses were measured according to the European Carotid Surgery Trial [ECST] method). After a median interval of 9.4 months, a telephone follow-up was performed to determine their outcome. Dependency or death (modified Rankin scale-mRS >2) and all cause mortality were the study end-points. RESULTS: At follow-up, 158 patients had a mRS >2. In multivariate analysis, of 13 variables univariately predictive of dependency or death, only National Institutes of Health Stroke Scale (NIHSS) score (P < 0.0001), age (P < 0.0001) and ipsi- or contralateral carotid stenosis ≥60% (O.R. 3.5, 95% C.I. 1.5-8.6, P = 0.006) remained associated with a mRS >2. Sixty-nine patients had died. In a Cox proportional hazards regression, of 10 variables univariately predictive of mortality, only NIHSS score (P < 0.0001), age (P = 0.003), total anterior circulation syndrome (P = 0.004), vertebral Doppler abnormalities (O.R. 2.2, 95% C.I. 1.3-3.6, P = 0.006), male sex (P = 0.02), and hypercholesterolemia (P = 0.04, inverse relationship) remained associated with mortality. CONCLUSIONS: In stroke patients, carotid stenoses ≥60%, ipsi- or contralateral to cerebral lesions, were associated with an increased medium and long-term probability of dependency or death, and abnormalities of vertebrobasilar flow were a significant indicator of death risk, independent of stroke severity and age.

Risk Factors for Lacunar Strokes with Visible Cerebral Lesions on Computed Tomography Scan.

BACKGROUND: The aim of this study was the detection of risk factors for lacunar strokes with visible lesions on computed tomography (CT) scan, considering in particular clinical characteristics, echocardiographic parameters, and carotid-femoral pulse wave velocity (PWV, a marker of large-artery stiffness). Lacunar strokes with very small or nonvisible lesions may have different risk factors. METHODS: We examined 106 patients (mean age 66.9 ± 12.3 years, 60 men), including 55 patients with clinically lacunar stroke associated with deep ischemic lesions of .3-1.5 cm on brain CT scan, and 51 control patients with cortical ischemic stroke, with lesions of 2.5-10.0 cm. RESULTS: In multiple logistic regression, with respect to cortical strokes, the following variables were independently associated with lacunar strokes: tricuspid regurgitation velocity (inverse relationship, odds ratio [OR] .13, 95% confidence interval [CI] .04-.43, P = .0007, cutoff at 228 cm/s), mean systolic blood pressure (SBP) (OR 3.98, 95% CI 2.78-7.79, P = .008, cutoff at 145 mmHg), ever-smoker status (OR 2.68, 95% CI 1.06-6.80, P = .04), and atrial fibrillation (inverse relationship, OR .11, 95% CI .01-1.00, P = .0496). In univariate analysis, the patients with lacunar stroke also had a lower prevalence of mitral regurgitation. There were no differences between the 2 groups in relation to diabetes, cholesterol, left ventricular mass and dimensions, and PWV. CONCLUSIONS: The patients with lacunar strokes with visible cerebral lesions on CT scan, compared with the patients with cortical infarct, had a lower tricuspid regurgitation velocity, a higher mean SBP, a greater prevalence of ever-smokers, and a lower prevalence of atrial fibrillation.