Plasma clusterin and lipid profile: a link with aging and cardiovascular diseases in a population with a consistent number of centenarians

The role of Clusterin in attenuation of inflammation and reverse cholesterol transfer makes this molecule a potential candidate as a marker for cancer, cardiovascular disease, diabetes mellitus, and metabolic syndrome. In elderly subjects cardiovascular diseases represent the primary cause of death and different clinical studies have shown a positive correlation of these diseases with changes in the lipid pattern. This work aimed at evaluating the relationship between circulating clusterin and the biochemical parameters that characterize the lipid profile of a Sardinian population divided into five age groups including centenarians; the high frequency in Sardinia of these long-lived individuals gave us the opportunity to extend the range of the age groups to be analyzed to older ages and to better evaluate the changes in the lipid balance during ageing and its relationship with clusterin concentration in plasma. Our results showed that Clusterin concentration values of the youngest group were more similar with the centenarian’s group compared to the other age groups, and a positive correlation arises with LDL. Furthermore given the high prevalence of cardiovascular diseases in the population examined and the association of Clusterin with these pathologies we evaluated Clusterin concentration variation in two groups with or without cardiovascular diseases. In presence of cardiovascular disease, Clusterin is significantly related to the most atherogenic components of lipid profile (total cholesterol and LDL), especially in women, suggesting its potential role in modulating cardiovascular metabolic risk factors

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Ageing induces left ventricular concentric remodelling in normotensive subjects

Objective: To assess whether age affects left ventricular anatomy independently of age-related hypertension or concomitant heart diseases. Design and methods: In 430 consecutive normotensive and clinically healthy subjects aged 16-85 years we obtained echocardiographic measurements of left ventricular posterior wall thickness, internal diameter, relative wall thickness, Penn mass index and systemic haemodynamics. The pulse pressure: stroke volume ratio was calculated as an estimate of systemic arterial stiffness. The subjects were divided into three age groups: +/- 40 (group 1, n = 137), 41-64 (group 2, n = 261) and +/- 65 years (group 3, n = 32). Results: Systolic blood pressure increased from group 1 to group 3, as did the pulse pressure: stroke volume ratio and posterior wall thickness, whereas the left ventricular internal diameter was less in group 3 than in groups 1 and 2. The relative wall thickness increased from group 1 to groups 2 and 3, whereas the left ventricular mass index did not differ among age groups. Age was related positively to the systolic blood pressure, pulse pressure: stroke volume ratio, posterior wall thickness index and relative wall thickness, and negatively to the left ventricular internal diameter but not to the left ventricular mass index. Conclusions: In healthy adults, relative wall thickness increases with age whereas left ventricular mass does not change. The concentric remodelling of left ventricular geometry parallels age-related stiffening of the arterial tree, elevation of systolic blood pressure and decrease in left ventricular volume. Thus partition values of relative wall thickness should be adjusted for age.</br

Carotid intimal-medial thickness and stiffness are not affected by hypercholesterolemia in uncomplicated essential hypertension

The combined effects of hypertension and hypercholesterolemia on carotid anatomy and stiffness were studied in 62 normotensives, 141 uncomplicated essential hypertensives with a total cholesterol level &lt;240 mg/dL, and 60 essential hypertensives with a total cholesterol level 240 mg/dL. Carotid ultrasonography was performed to evaluate intimal-medial thickness (IMT), relative wall thickness, and the presence of plaque. Carotid pressure waveforms were recorded by applanation tonometry to measure carotid stiffness (ß) and pressure wave reflection (ie, augmentation index). After adjusting for age, body mass index, and smoking habit by analysis of covariance, no significant differences were found between normocholesterolemic hypertensives and hypercholesterolemic hypertensives in terms of IMT (0.79±0.19 versus 0.81±0.19 mm), relative wall thickness (0.27±0.07 versus 0.28±0.07), carotid stiffness (6.1±3.2 versus 5.6±2.7), augmentation index (18.7±12.9% versus 17.3±12.8%), and prevalence of plaque (30.8% versus 30.7%). In the whole population, carotid IMT was significantly related to age (r=0.43), systolic (r=0.35) and diastolic (r=0.35) blood pressures, body surface area (r=0.22), and cholesterol levels (r=0.22) (all P&lt;0.05). Carotid stiffness was significantly related to age, blood pressure, body mass index, and body surface area but not to cholesterol levels. In multivariate analyses, age, body surface area, and systolic blood pressure, but not cholesterol, smoking habit, or sex, were independent correlates of IMT (multiple R=0.54, P&lt;0.0001), whereas carotid stiffness was independently associated with age, body surface area, and sex (R=0.38, P&lt;0.0001). In conclusion, hypertension is a potent stimulus of vascular hypertrophy. The superimposition of hypercholesterolemia does not substantially augment these changes or further increase arterial stiffness in uncomplicated hypertensive subjects

Assessment of left ventricular function by the midwall fractional shortening/end-systolic stress relation in human hypertension

AbstractObjectives. This study examined left ventricular performance in relatively unselected hypertensive patients by use of physiologically appropriate midwall shortening/end-systolic stress relations.Background. Supranormal left ventricular function has been reported in hypertensive patients, possibly due to an artifact of mismatching endocardial rather than midwall fractional shortening to mean left ventricular end-systolic stress.Methods. Samples of 474 hypertensive patients (150 women, 324 men) and 140 normal subjects (68 women, 72 men) were drawn from a large urban employed population. The inverse relations (p < 0.0001) of both echocardiographic endocardial and midwall fractional shortening to end-systolic stress in normal subjects were used to calculate the ratios of observed to predicted endocardial and midwall fractional shortening in hypertensive patients. Midwall shortening was calculated from an elliptic model, taking into account the epicardial migration of the midwall during systole.Results. Use of midwall fractional shortening in hypertensive patients reduced the proportion of patients with function above the 95th percentile of normal from 22% to 4% (p < 0.0001) and fractional shortening as a percent of predicted from 107% (p < 0.001 vs. 100% in normotensive control subjects) to 95% (p < 0.0001; p < 0.001 vs. 101% in normotensive control subjects). Midwall shortening was below the 5th percentile of normal in 16% of hypertensive patients instead of 2% with endocardial shortening (p < 0.0001): They tended to be older than other hypertensive patients and had concentric left ventricular hypertrophy. Among hypertensive patients, these with concentric left ventricular hypertrophy or remodeling had reduced midwall shortening as a percent of predicted from end-systolic stress (p < 0.0001).Conclusions. Use of the physiologically more appropriate mid-wall shortening/end-systolic stress relation 1) markedly reduces the proportion of hypertensive subjects identified as having high endocardial left ventricular functions; and 2) identifies a substantial subgroup of patients with reduced left ventricular function who have concentric geometry of the left ventricle, a pattern associated with high cardiovascular risk