Abstract Gut microbiota establishment and further microbiota shifts are very important for maintaining host health throughout life. There are some factors, including genetics, the mother's health and ...diet, delivery mode, breast or formula feeding, that may influence the gut microbiota. By the end of approximately the first 3 y of life, the gut microbiota becomes an adult-like stable system. Once established, 60 to 70% of the microbiota composition remains stable throughout life, but 30 to 40% can be altered by changes in the diet and other factors such as physical activity, lifestyle, bacterial infections, and antibiotic or surgical treatment. Diet-related factors that influence the gut microbiota in people of all ages are of great interest. Nutrition may have therapeutic success in gut microbiota correction. This review describes current evidence concerning the links between gut microbiota composition and dietary patterns throughout life.
Patients with heart failure with preserved ejection fraction were assigned to receive sacubitril–valsartan or valsartan. At a median of 35 months, there was no significant between-group difference in ...the composite outcome of total hospitalizations for heart failure or death from cardiovascular causes.
BACKGROUND:While disease-modifying therapies exist for heart failure (HF) with reduced left ventricular ejection fraction (LVEF), few options are available for patients in the higher range of LVEF ...(>40%). Sacubitril/valsartan has been compared with a renin-angiotensin-aldosterone–system inhibitor alone in 2 similarly designed clinical trials of patients with reduced and preserved LVEF, permitting examination of its effects across the full spectrum of LVEF.
METHODS:We combined data from PARADIGM-HF (LVEF eligibility≤40%; n=8399) and PARAGON-HF (LVEF eligibility≥45%; n=4796) in a prespecified pooled analysis. We divided randomized patients into LVEF categories≤22.5% (n=1269), >22.5% to 32.5% (n=3987), >32.5% to 42.5% (n=3143), > 42.5% to 52.5% (n=1427), > 52.5% to 62.5% (n=2166), and >62.5% (n=1202). We assessed time to first cardiovascular death and HF hospitalization, its components, and total heart failure hospitlizations, all-cause mortality, and noncardiovascular mortality. Incidence rates and treatment effects were examined across categories of LVEF.
RESULTS:Among 13 195 randomized patients, we observed lower rates of cardiovascular death and HF hospitalization, but similar rates of noncardiovascular death, among patients in the highest versus the lowest groups. Overall sacubitril/valsartan was superior to renin-angiotensin-aldosterone–system inhibition for first cardiovascular death or heart failure hospitalization (Hazard Ratio HR 0.84 95% CI, 0.78–0.90), cardiovascular death (HR 0.84 95% CI, 0.76–0.92), heart failure hospitalization (HR 0.84 95% CI, 0.77–0.91), and all-cause mortality (HR 0.88 95% CI, 0.81–0.96). The effect of sacubitril/valsartan was modified by LVEF (treatment-by-continuous LVEF interaction P=0.02), and benefit appeared to be present for individuals with EF primarily below the normal range, although the treatment benefit for cardiovascular death diminished at a lower ejection fraction. We observed effect modification by LVEF on the efficacy of sacubitril/valsartan in both men and women with respect to composite total HF hospitalizations and cardiovascular death, although women derived benefit to higher ejection fractions.
CONCLUSIONS:The therapeutic effects of sacubitril/valsartan, compared with a renin-angiotensin-aldosterone–system inhibitor alone, vary by LVEF with treatment benefits, particularly for heart failure hospitalization, that appear to extend to patients with heart failure and mildly reduced ejection fraction. These therapeutic benefits appeared to extend to a higher LVEF range in women compared with men.
CLINICAL TRIAL REGISTRATION:https://www.clinicaltrials.gov. Unique identifiersNCT01920711 (PARAGON-HF), NCT01035255 (PARADIGM-HF).
The prevalence of familial hypercholesterolemia (FH) in Russia has not previously been evaluated. The aim of our study was to investigate the prevalence of FH in the population of the West Siberian ...region of Russia, and then estimate the frequency of coronary artery disease (CAD) and treatment with cholesterol-lowering medication in FH patients.
The sample of our study consisted of participants from the population-based cohort of The Epidemiology of Cardiovascular Risk Factors and Diseases in Regions of the Russian Federation Study (ESSE-RF), conducted in the Tyumen and Kemerovo regions (1,630 and 1,622 people, respectively, aged 25-64). All participants who had LDL-cholesterol higher than 4.9 mmol/l and who had LDL-cholesterol less than or equal to 4.9 mmol/l but had statin therapy were examined and interviewed by experts in FH.
The prevalence of patients with definite FH was 0.24% (one in 407) (95% confidence interval CI: 0.06%-0.42%), with probable FH was 0.68% (one in 148) (95% CI: 0.38%-0.98%), and with definite or probable FH combined was 0.92% (one in 108) (95% CI: 0.58%-1.26%). 40% (95% CI: 20.8%-59.2%) of patients with definite or probable FH had CAD. However, only 23% (95% CI: 6.3%-39.7%) of patients with definite or probable FH were on statins. The odds ratios for CAD and myocardial infarction (MI), adjusted for age, gender, region, smoking, hypertension, and diabetes mellitus, were 3.71 (95% CI: 1.58-8.72) (p = 0.003) and 4.06 (95% CI: 0.89-18.55) (р = 0.070) respectively for individuals with definite or probable FH relative to those who were unlikely to have FH.
The prevalence of FH in Russia may be significantly higher than previously estimated. There is underdiagnosis and undertreatment of FH in Russia.
Lipoprotein(a) (Lp(a)) is recognized as an independent risk factor for atherosclerotic cardiovascular disease (ASCVD). The aim of this study was to estimate the distribution of Lp(a) levels in ...working age adults from the Russian population and to assess its association with ischemic heart disease (IHD), myocardial infarction (MI), stroke, diabetes mellitus (DM), and arterial hypertension (AH).
This substudy of the population-based study "Epidemiology of Cardiovascular Diseases and their Risk Factors in Some Regions of the Russian Federation" (ESSE-RF) included 8461 subjects aged 25-64 years (63.7% women) without lipid-lowering drugs. Atherosclerotic cardiovascular disease was self-reported. Lp(a), apolipoproteins AI and B, and lipid and glucose levels in blood serum were determined.
The prevalence of Lp(a) ≥ 30 mg/dl was 20.5% and 23.0%, and prevalence of Lp(a) ≥ 50 mg/dl was 13.3% and 15.2%, in men and women, respectively. An association of Lp(a) with IHD, MI, and AH, but not with stroke and DM, was shown. A cut-off level of Lp(a) of 9 mg/dl was determined, above which there was increased frequency of MI (by 59.2%,
= 0.02), IHD (by 33.4%,
< 0.001), and AH (by 11.6%,
< 0.001). In the multivariate analysis only the association of Lp(a) with IHD (1.19 (1.01-1.41),
= 0.038) and MI (1.57 (1.06-2.38),
= 0.028) remained significant.
Lipoprotein(a) level ≥ 30 mg/dl was detected in every fifth adult aged 25-64 years. Increased risk of MI and IHD starts at an Lp(a) serum level above 9 mg/dl.
The role of plasma cholesterol in impairing arterial function and elasticity remains unclear. We evaluated arterial stiffness, measured locally in the common carotid artery by high-resolution ...echo-tracking, and aortic stiffness, using carotid-femoral pulse wave velocity (PWV) (the "gold-standard" measurement of arterial stiffness), in treatment-naive patients with heterozygous familial hypercholesterolemia (FH).
The study included 66 patients with FH (10-66 years old) and 57 first-degree relatives without FH (11-61 years old). Carotid-femoral PWV was determined by SphygmoCor (AtCor, Australia). The parameters of carotid stiffness β-index, Peterson elastic modulus and local PWV were assessed with regard to the common carotid artery at a distance of 1cm from the bifurcation (AlokaProsound Alpha7, Japan).
FH patients showed significantly higher β-index (6.3(4.8-8.2) vs. 5.2(4.2-6.4), p = 0.005), Ep (78(53-111) kPa vs. 62(48-79) kPa, p = 0.006), local PWV (5.4(4.5-6.4) m/c vs. 4.7(4.2-5.4) m/c, p = 0.005), but comparable values of carotid-femoral PWV (6.76(7.0-7.92) m/c vs. 6.48(6.16-7.12) m/c, p = 0.138). Carotid arteries and the aorta stiffened with age in patients with FH, but after 30 years, carotid arteries stiffened more significantly than the aorta.
Our study demonstrated that treatment-naive patients with FH had stiffer carotid arteries than their relatives, but showed no difference in aortic stiffness. We also found out that the rate of reduction of elasticity of the aorta and carotid arteries in FH patients varies: it is observed earlier in carotid arteries than in the aorta.
Ways for reducing mortality from cardiovascular diseases The article analyzes the possible ways to further reduce cardiovascular disease mortality in the Russian Federation by eliminating ...shortcomings and pitfalls, introducing known but not used opportunities, and new organizational and medical technologies based on the accumulated experience of "best practice".
To describe the baseline characteristics of patients with heart failure and preserved left ventricular ejection fraction enrolled in the PARAGON-HF trial (Prospective Comparison of Angiotensin ...Receptor Neprilysin Inhibitor With Angiotensin Receptor Blocker Global Outcomes in HFpEF) comparing sacubitril/valsartan to valsartan in reducing morbidity and mortality.
We report key demographic, clinical, and laboratory findings, and baseline therapies, of 4822 patients randomized in PARAGON-HF, grouped by factors that influence criteria for study inclusion. We further compared baseline characteristics of patients enrolled in PARAGON-HF with those patients enrolled in other recent trials of heart failure with preserved ejection fraction (HFpEF). Among patients enrolled from various regions (16% Asia-Pacific, 37% Central Europe, 7% Latin America, 12% North America, 28% Western Europe), the mean age of patients enrolled in PARAGON-HF was 72.7±8.4 years, 52% of patients were female, and mean left ventricular ejection fraction was 57.5%, similar to other trials of HFpEF. Most patients were in New York Heart Association class II, and 38% had ≥1 hospitalizations for heart failure within the previous 9 months. Diabetes mellitus (43%) and chronic kidney disease (47%) were more prevalent than in previous trials of HFpEF. Many patients were prescribed angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (85%), β-blockers (80%), calcium channel blockers (36%), and mineralocorticoid receptor antagonists (24%). As specified in the protocol, virtually all patients were on diuretics, had elevated plasma concentrations of N-terminal pro-B-type natriuretic peptide (median, 911 pg/mL; interquartile range, 464-1610), and structural heart disease.
PARAGON-HF represents a contemporary group of patients with HFpEF with similar age and sex distribution compared with prior HFpEF trials but higher prevalence of comorbidities. These findings provide insights into the impact of inclusion criteria on, and regional variation in, HFpEF patient characteristics.
URL: https://www.clinicaltrials.gov. Unique identifier: NCT01920711.
With advancing age the left ventricle (LV) undergoes structural and functional changes, thereby creating the substrate for the development of diseases. One possible mechanism of the ageing heart is a ...cellular senescence. Leukocyte telomere length (LTL) is a marker of replicative ageing. The purpose of this study was to evaluate the structure and function of the LV in people of different ages free of cardiovascular diseases (CVD) and regular drug medication and to assess their relationship with LTL. We hypothesized that age-related changes in LV myocardium are associated with telomere length.
The study population consisted of 150 healthy, non-obese volunteers aged 28 to 78 years without history of CVD, significant deviations by 12-lead electrocardiogram and negative exercise test (treadmill stress test). All the participants underwent standardized transthoracic echocardiography using an available system (iE33; Philips). The LTL was measured by real-time quantitative polymerase chain reaction. We determined the relative ratio of telomere repeat copy number (T) to single-copy gene copy number (S).
In the older people there was a higher wall thickness than in the younger (1.03 ± 0.09 vs. 0.88 ± 0.10, p<0.01), whereas LV mass index was comparable between them (85.8 ± 15.40 vs. 83.1 ± 11.8, p = 0.20). There was a decrease in LV dimensions with advancing age (p<0.001). Older subjects had impairment in LV relaxation. LTL was associated with decreased E/A, Em/Am ratio (β = -0.323, p = 0.0001) after adjusting for age, sex and risk factors. There is no relation between the LTL and the structure of LV.
Our data suggest that the ageing process leads to changes in LV structure and diastolic function and is linked with a phenotype of concentric LV remodeling. Telomere attrition is associated with age-related LV diastolic dysfunction. Telomere length appears to be a biomarker of myocardial ageing.
The article is devoted to the analysis of changes in the role of causal and comorbid risk factors for two main types of heart failure with reduced and preserved ejection fraction over the previous 20 ...years. Within the same time interval, the dynamics of the prevalence and mortality for these clinical variants. Special attention is paid to a possible solution to the issue of the complexity of recording cases of diagnosis and treatment of chronic heart failure in outpatient and hospital practice.
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