In a trial comparing 100 mg of aspirin with placebo in nearly 20,000 community-dwelling persons 70 years of age or older in Australia and the United States, aspirin use had no effect on the rate of ...survival free from dementia or physical disability.
After a median follow-up of 4.7 years, there were 1.6 more deaths per 1000 person-years among healthy older adults who were randomly assigned to receive aspirin than among those who received placebo. ...Cancer-related death accounted for much of the excess mortality.
In older persons without known cardiovascular disease, the use of low-dose aspirin resulted in a significantly higher risk of major hemorrhage and did not result in a significantly lower risk of ...cardiovascular disease than placebo.
In light of the worldwide epidemic of obesity, and in recognition of hypertension as a major factor in the cardiovascular morbidity and mortality associated with obesity, The Obesity Society and The ...American Society of Hypertension agreed to jointly sponsor a position paper on obesity‐related hypertension to be published jointly in the journals of each society. The purpose is to inform the members of both societies, as well as practicing clinicians, with a timely review of the association between obesity and high blood pressure, the risk that this association entails, and the options for rational, evidenced‐based treatment. The position paper is divided into six sections plus a summary as follows: pathophysiology, epidemiology and cardiovascular risk, the metabolic syndrome, lifestyle management in prevention and treatment, pharmacologic treatment of hypertension in the obese, and the medical and surgical treatment of obesity in obese hypertensive patients. Obesity (2012)
The association between glomerular hyperfiltration and cardiovascular events is not well known. To investigate whether glomerular hyperfiltration is independently associated with risk of adverse ...outcome we analyzed 8794 participants, average age 52 years enrolled in 8 prospective studies. Of these, 89% had hypertension. Using the 5th and 95th percentiles of the age- and sex-specific quintiles of CKD-EPI-calculated estimated glomerular filtration rate (eGFR), we identified three participant groups with low, high and normal eGFR. The ambulatory pulse pressure interval was wider and nighttime blood pressure fall was smaller in both the low and high than in the normal eGFR participants. During a mean follow-up of 6.2 years, there were 722 cardiovascular events. Crude event rates were significantly higher for both high (1.8 per 100-person-year) and low eGFR groups (2.1 per 100 person-year) as compared with group with normal eGFR (1.2 per 100 person-year). In multivariable Cox models including age, sex, average 24-hour blood pressure, smoking, diabetes, and cholesterol, both high eGFR (hazard ratio 1.5 (95% confidence interval 1.2-2.1) and low eGFR (2.0 1.5-2.6) participants had a significantly higher risk of cardiovascular events as compared to those with normal eGFR. Addition of body mass index to the multivariable survival model did not change the magnitude of hazard estimates. Thus, glomerular hyperfiltration is a strong and independent predictor of cardiovascular events in a large multiethnic population of predominantly hypertensive individuals. Our findings support a U-shaped relationship between eGFR and adverse outcome.
Studies in animal models and in cultured cells have shown that fatty acids can induce alterations in the DNA methylation of specific genes. There have been no studies of the effects of fatty acid ...supplementation on the epigenetic regulation of genes in adult humans.
We investigated the effect of supplementing renal patients with 4 g daily of either n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) or olive oil (OO) for 8 weeks on the methylation status of individual CpG loci in the 5' regulatory region of genes involved in PUFA biosynthesis in peripheral blood mononuclear cells from men and women (aged 53 to 63 years). OO and n-3 LCPUFA each altered (>10% difference in methylation) 2/22 fatty acid desaturase (FADS)-2 CpGs, while n-3 LCPUFA, but not OO, altered (>10%) 1/12 ELOVL5 CpGs in men. OO altered (>6%) 8/22 FADS2 CpGs and (>3%) 3/12 elongase (ELOVL)-5 CpGs, while n-3 LCPUFA altered (>5%) 3/22 FADS2 CpGs and 2/12 (>3%) ELOVL5 CpGs in women. FADS1 or ELOVL2 methylation was unchanged. The n-3 PUFA supplementation findings were replicated in blood DNA from healthy adults (aged 23 to 30 years). The methylation status of the altered CpGs in FADS2 and ELOVL5 was associated negatively with the level of their transcripts.
These findings show that modest fatty acid supplementation can induce altered methylation of specific CpG loci in adult humans, contingent on the nature of the supplement and on sex. This has implications for understanding the effect of fatty acids on PUFA metabolism and cell function.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Context:
Obesity and related diseases have become a global public health burden. Identifying biomarkers will lead to a better understanding of the underlying mechanisms associated with obesity and ...the pathways leading to insulin resistance (IR) and diabetes.
Objective:
This study aimed to identify the lipidomic biomarkers associated with obesity and IR using plasma samples from a population-based cohort of young adults.
Design and Setting:
The Western Australian Pregnancy Cohort (Raine) study enrolled 2900 pregnant women from 1989 to 1991. The 20-year follow-up was conducted between March 2010 and April 2012.
Participants and Samples:
Plasma samples from 1176 subjects aged 20 years were analyzed using mass spectrometry-based metabolomics.
Main Outcome Measures:
Associations of analytes with markers of obesity and IR including body mass index, waist circumference, homeostasis model assessment (HOMA-IR), and insulin were examined. Analyses were stratified by body mass index and adjusted for lifestyle and other factors.
Results:
Waist circumference was positively associated with seven sphingomyelins and five diacylphosphatidylcholines and negatively associated with two lysophosphatidylcholines. HOMA-IR was negatively associated with two diacylphosphatidylcholines and positively with one lysophosphatidylcholine and one diacylphosphatidylcholine. No significant association was found in the obese/overweight group of the HOMA-IR model. In the normal-weight group, one lysophosphatidylcholine was increased.
Conclusion:
A possible discriminative effect of sphingomyelins, particularly those with two double bonds, and lysophosphatidylcholines was identified between subjects with normal weight and obesity independent of low-density lipoprotein cholesterol and high-density lipoprotein cholesterol concentrations. Our results suggest weight status-dependent mechanisms for the development of IR with lysophosphatidylcholine C14:0 as a key metabolite in nonobese IR.
The association of ambulatory blood pressure (BP) variability with mortality and cardiovascular events is controversial. To investigate whether BP variability predicts cardiovascular events and ...mortality in hypertension, we analyzed 7112 untreated hypertensive participants (3996 men) aged 52±15 years enrolled in 6 prospective studies. Median follow-up was 5.5 years. SD of night-time BP was positively associated with age, body mass index, smoking, diabetes mellitus, and average night-time BP (all P<0.001). In a multivariable Cox model, night-time BP variability was an independent predictor of all-cause mortality (systolic, P<0.001/diastolic, P<0.0001), cardiovascular mortality (P=0.008/<0.0001), and cardiovascular events (P<0.001/<0.0001). In contrast, daytime BP variability was not an independent predictor of outcomes in any model. In fully adjusted models, a night-time systolic BP SD of ≥12.2 mm Hg was associated with a 41% greater risk of cardiovascular events, a 55% greater risk of cardiovascular death, and a 59% increased risk of all-cause mortality compared with an SD of <12.2 mm Hg. The corresponding values for a diastolic BP SD of ≥7.9 mm Hg were 48%, 132%, and 77%. The addition of night-time BP variability to fully adjusted models had a significant impact on risk reclassification and integrated discrimination for all outcomes (relative integrated discrimination improvement for systolic BP variability: 9% cardiovascular events, 14.5% all-cause death, 8.5% cardiovascular death, and for diastolic BP variability: 10% cardiovascular events, 19.1% all-cause death, 23% cardiovascular death, all P<0.01). Thus, addition of BP variability to models of long-term outcomes improved the ability to stratify appropriately patients with hypertension among risk categories defined by standard clinical and laboratory variables.
OBJECTIVES:To explore the association of different types of blood pressure (BP) variability measures estimated from either short-term ambulatory reading-to-reading or long-term clinic visit-to-visit ...BP records with long-term survival in an elderly treated hypertensive population.
METHODS:A subset of patients (n = 508) aged at least 65-years was studied from the Second Australian National Blood Pressure study. We estimated SBP and DBP BP variability as the SD of ambulatory (24-h, daytime, night-time) and clinic visit-to-visit BP directly from all corresponding on-treatment within-individual BP records. Ambulatory ‘weighted day–night’ variability was calculated as a weighted mean of daytime and night-time SD. Cox-proportional hazard models adjusted for baseline risk factors (Model 1) and corresponding on-treatment BP (Model 2) or average night-time SBP (best predictive BP measure for outcome) (Model 3) were used to determine the relationship between long-term outcome and BP variability.
RESULTS:Over a median of 10.6 years, 101 patients died from any cause, of which 51 deaths were cardiovascular. We observed increase in ‘daytime’ and ‘weighted day–night’ SBP/DBP variability was significantly associated with increased all-cause mortality in all models. For cardiovascular mortality, only ‘weighted day–night’ SBP variability significantly predicted risk in all models (Model 3 hazard ratio1.09, 95% confidence interval1.00–1.19, P = 0.04). Long-term BP variability was not associated with any outcome. On direct comparison, both ‘daytime’ and ‘weighted day–night’ BP variability measures provided similar prognostic information.
CONCLUSION:Short-term ‘daytime’ and ‘weighted day–night’ SBP variability from ambulatory BP recordings was a better predictor of mortality in elderly treated hypertensive patients than long-term BP variability from visit-to-visit BP recordings.
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