Summary Uric acid is the end product of purine metabolism. Its immediate precursor, xanthine, is converted to uric acid by an enzymatic reaction involving xanthine oxidoreductase. Uric acid has been ...formerly considered a major antioxidant in human plasma with possible beneficial anti-atherosclerotic effects. In contrast, studies in the past two decades have reported associations between elevated serum uric acid levels and cardiovascular events, suggesting a potential role for uric acid as a risk factor for atherosclerosis and related diseases. In this paper, the molecular pattern of uric acid formation, its possible deleterious effects, as well as the involvement of xanthine oxidoreductase in reactive oxygen species generation are critically discussed. Reactive oxygen species contribute to vascular oxidative stress and endothelial dysfunction, which are associated with the risk of atherosclerosis. Recent studies have renewed attention to the xanthine oxidoreductase system, since xanthine oxidoreductase inhibitors, such as allopurinol and oxypurinol, would be capable of preventing atherosclerosis progression by reducing endothelial dysfunction. Also, beneficial effects could be obtained in patients with congestive heart failure. The simultaneous reduction in uric acid levels might contribute to these effects, or be a mere epiphenomenon of the drug action. The molecular mechanisms involved are discussed.
Microparticles (MPs) are small vesicles, ranging in size from 0.1 μm to 2 μm, originating from plasma membranes of endothelial cells, platelets, leukocytes and erythrocytes. MPs can transfer antigens ...and receptors to cell types that are different from their cell of origin. Circulating MPs provide a procoagulant aminophospholipid surface for the assembly of the specific enzymes of coagulation. Both tissue factor and phosphatidylserine are exposed on MP outer membranes. In addition, MPs can play a significant role in vascular function and inflammation by modulating nitric oxide and prostacyclin production in endothelial cells, and stimulating cytokine release and tissue factor induction in endothelial cells, as well as monocyte chemotaxis and adherence to the endothelium. Finally, increased levels of MPs have been found in the presence of acute coronary syndromes, ischemic stroke, diabetes, systemic and pulmonary hypertension, and hypertriglyceridemia. From a practical point of view, MPs could be considered to be important markers of cardiovascular risk, as well as surrogate end points for assessing the efficacy of new drugs and therapies.
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.
Cross-sectional and longitudinal study using data from 1116 older adults (72.6 ± 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.
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.
In our cohort of older adults, step test duration was the most relevant predictor of cognitive impairment.
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.
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 + or - 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 greater than or equal to 126 mg/dl (greater than or equal to 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 greater than or equal to 6.5% (greater than or equal to 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 greater than or equal to 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. Keywords: Diabetes, Outcome, Prognosis, Stress hyperglycemia, Stroke
An important role in atherogenesis is played by oxidative stress, which may be induced by common risk factors. Mitochondria are both sources and targets of reactive oxygen species, and there is ...growing evidence that mitochondrial dysfunction may be a relevant intermediate mechanism by which cardiovascular risk factors lead to the formation of vascular lesions. Mitochondrial DNA is probably the most sensitive cellular target of reactive oxygen species. Damage to mitochondrial DNA correlates with the extent of atherosclerosis. Several cardiovascular risk factors are demonstrated causes of mitochondrial damage. Oxidized low density lipoprotein and hyperglycemia may induce the production of reactive oxygen species in mitochondria of macrophages and endothelial cells. Conversely, reactive oxygen species may favor the development of type 2 diabetes mellitus, mainly through the induction of insulin resistance. Similarly - in addition to being a cause of endothelial dysfunction, reactive oxygen species and subsequent mitochondrial dysfunction - hypertension may develop in the presence of mitochondrial DNA mutations. Finally, other risk factors, such as aging, hyperhomocysteinemia and cigarette smoking, are also associated with mitochondrial damage and an increased production of free radicals. So far clinical studies have been unable to demonstrate that antioxidants have any effect on human atherogenesis. Mitochondrial targeted antioxidants might provide more significant results.
To ascertain whether carotid lesions are more prevalent in outpatients with incidental findings of nonalcoholic fatty liver disease (NAFLD) at abdominal ultrasound (US).
One hundred and fifty-four ...consecutive outpatients (age range 24-90 years, both sexes) referred by general practitioners for abdominal US, and drinking less than 20 g alcohol/day, underwent carotid US for an assessment of carotid intima-media thickness (c-IMT) and carotid plaque prevalence. Hepatic steatosis, visceral fat thickness and subcutaneous fat thickness were also assessed at ultrasonography.
Higher c-IMT values were found in the presence of NAFLD (90 patients), even after adjustment for indices of general and abdominal obesity and for the principal cardiovascular risk factors (0.84 +/- 0.10 mm vs 0.71 +/- 0.10 mm, P < 0.001). The prevalence of carotid plaques was 57.8% in the patients with NAFLD vs 37.5% in the patients without this condition (P = 0.02). The adjusted relative risk of having carotid plaques for patients with NAFLD was 1.85 (95% CI: 1.33-2.57, P < 0.001).
An incidental finding of hepatic steatosis may suggest the presence of silent carotid atherosclerotic lesions.
Cardiac troponins T and I (cTnT and cTnI) are the main markers of acute myocardial cell damage and then of Acute Coronary Syndrome (ACS) if associated with compatible symptoms. Although their ...cardio-specificity, the cTn may be increased in various clinical conditions but only few recent studies have reported their trends with age. This is a single-center retrospective observational study on two groups of adults consecutive patients, with age ≥65 years, admitted to the Emergency Department of the Sant'Orsola-Malpighi Hospital of Bologna, Italy, with chest pain as chief complaint. In the first group was dosed cTnT (N=617), in the second group cTnI (N=569). The patients with final ACS’s diagnosis (N=255) or an incomplete report of blood tests (N=17) were excluded. The definitive database included 471 patients in the first group and 443 in the second one. The observed differences between clinical parameters, patients with cTnT≤14ng/L and those with cTnT>14ng/L (N=207, 44%) are: older age, greater prevalence of diabetes, lower values of Hb e ALT, higher values of white blood cells, INR, glycemia, urea, creatinine, BNP e PCR. In multiple logistics regression (N=333) only 4 variables resulted independently associated to cTnT increase: age (P<0.0001), PCR (P=0.01), creatinine (P=0.02) and urea (P=0.04), R2=0.30. The differences between patients with cTnI≤40ng/L and those with cTnI>40ng/L (N=46, 10%) are: older age, Hb values equal and higher values of white blood cells, INR, glycemia, urea, creatinine, total bilirubin, AST, BNP e PCR. In multiple logistics regression (N=259) the only 4 variables independently associated to increase of cTnI are age (P<0.0001), glycemia (P=0.004), PCR (P=0.01) and white blood cells (P=0.02), R2=0.17. Furthermore, the number of patients with high level of cTn significantly increase by age (cTnT: 65-74 years 22.2%, 75-84 years 48.5%, ≥85 years 79.5%; cTnI: 65-74 years 4.3%, 75-84 years 8.1%, ≥85 years 22.5%, P<0.0001). In our study, cTnI showed fewer false positives than cTnT and seems to be less influenced by kidney failure. Furthermore, the acute phase of inflammation was associated with the rise of troponins. High cTn values were found in elderly subjects, without acute coronary syndromes, particularly cTnT. Then the age seems to be the most important factor related to this highelevated troponin levels.
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