[Relationship of retinal vascular caliber with age and cardiometabolic diseases in the population over 50 years of age]. / Svyaz' kalibra retinal'nykh sosudov s vozrastom i kardiometabolicheskimi zabolevaniyami v populyatsii starshe 50 let.

In an aging society, age-dependent diseases with high mortality, including cardiovascular diseases (CVD) and type 2 diabetes mellitus (DM2), occupy a special place. There is only limited population-based data on the relationship between cardiometabolic diseases and target-organ damage, including ocular microvasculature. PURPOSE: To explore the associations between the caliber of retinal vessels and cardiometabolic diseases in a population sample of men and women from middle-aged to elderly (Novosibirsk). MATERIAL AND METHODS: The subjects were participants of the Russian cohort - part of the international project HAPIEE, and were initially examined in 2003-2005 (n=9360, aged 45-69 years, Novosibirsk). At the third survey in 2015-2017, a random sub-sample of men and women (n=1011) was formed for an in-depth evaluation. We performed a calibrometric analysis involving measurement of central retinal artery equivalent (CRAE), central retinal vein equivalent (CRVE), and CRAE-to-CRVE ratio (AVR). RESULTS: In a population sample of men and women aged 55-84 years, age increment is accompanied by a decrease in the calibers of retinal arterioles and venules (p<0.001). Arterial hypertension (AH) was accompanied by a decrease in CRAE, CRVE (p=0.001) and AVR (p<0.001); the associations between AH, CRAE and AVR were independent from other factors. Multivariate analysis showed that CRAE and CRVE were inversely associated with the presence of DM2 (p=0.026). Carotid atherosclerosis was accompanied by an increase in CRVE (p<0.002); this relationship was mainly attributed to age and metabolic factors. There were no associations between carotid atherosclerosis and either CRAE or AVR. The multivariate analysis identified the weak positive associations of CRAE and AVR with the presence of ischemic heart disease and CVD. CONCLUSION: In the examined population sample aged 55-84 years, a number of associations were detected between retinal vascular caliber and cardiometabolic diseases. The observed changes in the microvascular bed of the retina may be important for prognosis of the course of common cardiometabolic diseases.

[Age-related characteristics of retinal vessels in aging (literature review).]

The changes of retinal vascular caliber and microvascular topography reflect the cumulative response to ageing, the influence of cardiovascular risk factors, inflammation, endothelial dysfunction. With objective to perform a systematic review of the studies which evaluate retinal vessels in ageing, we conducted the search of published reports (2003-2020). The review provided the evidence of narrowing of the caliber of retinal arterioles and venules in ageing; inverse relationship has been found in ethnically heterogeneous populations in a wide age range from 4th to 9th decade. The age dynamics of arteriovenous ratio (AVR) is evaluated less consistently. The available data showed the loss of complexity of the retinal microcirculatory bloodstream in elderly age, which might lead to a decrease in functional activity of microcirculation; however the studies are limited for systematic conclusions. The large population studies in Russia on this topic are practically absent. The researches of the microvascular retinal bloodstream in aging using the automatic analysis of the modern range of indicators, are relevant in the Russian population and will provide new data.

[The frequency and profile of drug treatment in subjects with dyslipidemias and cardimetabolic diseases in an urban russian population older then 55 years].

Aim      To analyze frequency and profile of the lipid-lowering therapy (LLT) in patients with dyslipidemia (DLP) and cardiometabolic diseases (CMD) in a population sample aged 55-84 years at the current time (2015-2017).Material and methods  Despite guidelines on DLP treatment and the availability of effective and safe lipid-lowering drugs, control of DPL in primary and secondary prevention of cardiovascular diseases (CVD) is insufficient. Knowledge of the level of pharmaceutical correction of DLP in the Russian population is limited; it requires an LLT assessment in various regions and in a wide age range, and a regular monitoring taking into account changing approaches to the correction of DLP. A random population of men and women aged 55-84 years (n=3 896) was evaluated in Novosibirsk in 2015-2017 (project HAPIEE). A joint DLP category was established as low-density lipoprotein cholesterol (LDL-C) ≥3.0 mmol/l, or total cholesterol (TC) ≥5.0 mmol/l, or triglycerides (TG) ≥1.7 mmol/l, or LLT. The combined group of DLP and CMD included ischemic heart disease (IHD), type 2 diabetes mellitus (DM2), and DLP. Regular LLD treatment for the recent 12 months, excluding the dosage of medicines, was assessed using the Anatomic Therapeutic Chemical (ATC) classification. The conditional control of serum lipids was taken as the achievement of LDL-C <3.0 mmol/l, TC <5.0 mmol/l, and TG <1.7 mmol/l.Results In the study sample, the total prevalence of DLP and CMD was 88 % (82.8 % for men and 91.3 % for women, p<0.001). 48.3% of patients in the IHD group, 35.0% in the DM2 group, 29.4% in the DLP group, and 32.8% in the CMD group took LLT. Control of serum lipids was achieved in 18.3% (37.9 % of patients on LLT) of patients with IHD; 9 % (25.6 % of patients on LLT) of patients with DM2; 7.3 % (24.8 % of patients on LLT) of patients with DLP; and 9.0 % (27.6 % of patients on LLTсреди) in the DLP and CMD group. Women with DM2 and DLP more frequently achieved lipid control than men (p<0.001). 98.7 % of study participants took statins as LLT.Conclusion      In the sample of urban population aged 55-84 years in 2015-2017, 90 % of patients had DLP or CMD, and at least ¾ of them required blood lipid control. The lipid control was achieved in every fifth IHD patient and in approximately 40% of those who took LLT. For DM2 or DLP patients, the lipid control was achieved in every tenth patient and in approximately 25% of those receiving LLT. Frequency of lipid control in IHD patients was comparable for men and women; in DM2 and DLP, men less frequently achieved the lipid control than women. About 70% of patients in the combined DLP and CMD group and more than 50% of IHD patients did not take LLT, which considerably contributed to the insufficient lipid control in primary and secondary prevention of atherosclerotic CVDs in this population.

[The changes of left ventricular longitudinal systolic function depending on hypertension and its control: analysis in a population].

Aim To evaluate changes in left ventricular (LV) systolic function by LV myocardial global longitudinal strain (GLS) and global strain rate (GSR) in patients with arterial hypertension (AH) and based on the effectiveness of blood pressure (BP) control in a Russian population sample of individuals older than 55 years.Materials and methods This cross-sectional study was a population-based cohort study (HAPIEE, Novosibirsk). LV myocardial GLS and GSR were studied by echocardiography in a random sample (n=1004, 55-84 years). Statistical analysis was performed with multivariate models of logistic regression.Results AH prevalence in the study sample was 78.4 %. Mean GLS was 19.1 % (SD, 4.07), which was less for men than for women (p=0.001). Mean GSR was 0.86 s-1 (SD, 0.19) and was not different between men and women. In individuals with AH, the GLS absolute value was lower than in normotensive people (18.8 %; SD, 4.04 vs. 20.2 %; SD, 4.03, p˂0.001); these differences remained irrespective of the age, gender, body weight index (BWI) (p=0.027), and LV mass index (p=0.05). When people with AH were divided into groups, the lowest GLS absolute values were observed among "ineffectively treated" or not receiving any therapy individuals (p<0.001 vs. normotensive group). AH 1.6 times increased the risk of LV GLS decrease. In individuals with AH, the GSR absolute value was lower than in normotensive people (- 0.85 s-1 (SD, 0.19) vs.- 0.92 s-1 (SD, 0.18), p<0.001); this difference remained in multivariate models. The lowest GSR absolute values were observed in the "ineffectively treated" group irrespective of the gender, age, and BWI (p=0.036 vs. normotensive group). AH doubled the risk of LV GSR decrease, which could be partially explained by the contribution of BWI and myocardial mass index.Conclusion In this population sample, LV GLS and GSR were independently associated with AH. The lowest GLS and GSR values were observed for ineffectively treated" individuals with AH, which may reflect an early decline of LV systolic function with inadequate control of AH.

[C-reactive protein and its associations with сardiometabolic risk factors and echocardiographic indicators of heart failure: results of "Know your heart" study in Arkhangelsk].

Aim To evaluate the relationship between high-sensitivity C-reactive protein (hsCRP) and echocardiographic (EchoCG) indicators of heart failure (HF) among adult population of the North region of Russia.Material and methods The Know Your Heart transversal study was performed in 2015-2017 on a random sample of adult population of Arkhangelsk aged 35-69 years (n=2381). The exclusion criterion for this study was a concentration of hsCRP >10 mg/l. The group of subclinical inflammation included 686 participants with hsCRP ≥2.0 mg/l; the comparison group consisted of 1158 participants with hsCRP <2.0 mg/l. Analysis included cardiometabolic risk factors, EchoCG indexes of left ventricular (LV) systolic and diastolic function and biomarkers (NT-proBNP, hsTroponin Т, cystatin С). Linear and logistic regressions were used.Results The group with hsCRP ≥2.0 mg/l had higher rates of arterial hypertension, diabetes mellitus, HF, and myocardial infarction in history than the comparison group. The hsCRP level was independently associated with waist circumference (ß=0.379, p <0.001), male gender (ß=-0.135, p<0.001), smoking (ß=0.109, p<0.001), triglycerides (ß=0.083, p<0.001), diastolic blood pressure (ß=0.082, p<0.001), cystatin C (ß=0.082, p<0.001), glycated hemoglobin (ß=0.064, p=0.003), and low-density lipoproteins (LDL) (ß=0.049, p=0.025). Independent predictors of subclinical inflammation included older age, smoking, abdominal obesity, elevated values of LDL (>3.0 mmol/l), triglycerides (>1.7 mmol/l), and cystatin C (>1.2 mg/l). hsCRP was independently negatively associated with LV ejection fraction, left atrial volume index, ratio of early to late LV diastolic filling velocity (p=0.003, p=0.002, p=0.005, respectively), which reflected the relationship of the increased content of hsCRP with impairment of LV systolic and diastolic function. A relationship between heart remodeling indexes and hsCRP concentration was shown.Conclusion In a sample of adult population from the North region of Russia, the hsCRP concentration was independently associated with cardiometabolic risk factors and structural and functional changes in the heart detected by EchoCG, which reflects a potential contribution of inflammation to heart remodeling and development of HF.

[The profile of drug treatment in subjects aged over 50 years with hypertension in an urban russian population].

Objective To analyze a profile of hypotensive drug therapy in patients with arterial hypertension (АH) aged 55-84 in a sample of urban population at a current period of time (2015-2017).Materials and Methods AH is a leader among risk factors of cardiovascular diseases (CVD) due to its high prevalence and serious prognosis. Despite the availability of effective hypotensive drugs and guidelines on AH treatment, 50% of patients do not achieve blood pressure (BP) goals. Knowledge about drug correction of AH in the Russian population is limited to clinical studies. Taking into account changing approaches in management of patients with AH, the population-based evaluation of hypotensive treatment if relevant. A random population sample of males and females aged 55-84 (n=3.898) was evaluated in Novosibirsk in 2015-2017 (international project, Health, Alcohol and Psychosocial Factors in Eastern Europe (HAPIEE)). AH was diagnosed in presence of systolic BP ≥140 mm Hg or diastolic BP ≥90 mm Hg and/or treatment with hypotensive drugs within the recent two weeks. Regular intake of medication for 12 months was evaluated with coding according to the Anatomic Therapeutic Chemical Classification System (АТХ / АТС).Results In the population sample aged 55-84, AH prevalence was 80.9 %, and 21.1 % of persons with AH did not receive drug therapy. Hypotensive medicines included (total/as a part of combination therapy) angiotensin-converting enzyme (ACE) inhibitors (42.3 % / 25.3 %), angiotensin II receptor blockers (ARBs) (30.3 % / 18.9 %), diuretics (22.6 % / 20.4 %), calcium channel blockers (20.2 % / 16.1 %), and beta-blockers (34.7 % / 27.6 %). 45.7 % of people with AH received a combination therapy. Effective BP control was achieved in 23.4 % of AH patients and in 29.6 % of patients receiving a hypotensive therapy. In the group of ineffective BP control, the proportion of females was lower, AH duration was longer, and blood glucose was higher than in the group of effective control.Conclusion In the sample of urban population aged 55-84 in 2015-2017, each fourth participant with AH and each third participant using hypotensive drugs achieved effective BP control. The therapy profile in AH patients included recommended drug classes. However, combination therapy was used insufficiently (50% of AH patients). By frequency of use, ACE inhibitors were on the first place, beta-blockers were on the second place, ARBs were on the third place, diuretics were on the fourth place, and calcium channel blockers were on the fifth place, which differed from the guidelines (the difference from the recommended priority ranking is that the drugs taking the first places in the guidelines were in fact on the 3rd and 4th places in their actual frequency of use). 20% of persons with AH did not receive hypotensive therapy, which significantly contributed to the insufficient BP control in the population.

Context-dependency of the relation between left ventricular mass and AGT gene variants.

In the European Project on Genes in Hypertension (EPOGH), we investigated in three populations to what extent in a family-based study, left ventricular mass (LVM) was associated with the C-532T and G-6A polymorphisms in the angiotensinogen (AGT) gene. We randomly recruited 221 nuclear families (384 parents and 440 offspring) in Cracow (Poland), Novosibirsk (Russia), and Mirano (Italy). Echocardiographic LVM was indexed to body surface area, adjusted for covariables, and subjected to multivariate analyses, using generalized estimating equations and quantitative transmission disequilibrium tests in a population-based and family-based approach, respectively. We found significant differences between the two Slavic centres and Mirano in left ventricular mass index (LVMI) (94.9 vs 80.4 g/m2), sodium excretion (229 vs 186 mmol/day), and the prevalence of the AGT -6A (55.7 vs 40.6%) and -532T (16.8 vs 9.4%) alleles. In population-based as well as in family-based analyses, we observed positive associations of LVMI and mean wall thickness (MWT) with the -532T allele in Slavic, but not in Italian male offspring. Furthermore, in Slavic male offspring, LVMI and MWT were significantly higher in carriers of the -532T/-6A haplotype than in those with the -532C/-6G or -532C/-6A allele combinations. In women, LVMI was neither associated with single AGT gene variants nor with the haplotypes (0.19 < P <0.98). In Slavic offspring carrying the AGT -532C/-6G or -532C/-6A haplotypes, LVMI significantly increased with higher sodium excretion (+3.5 g/m2/100 mmol; P=0.003), whereas such association was not present in -532T/-6A haplotype carriers (P-value for interaction 0.04). We found a positive association between LVMI and the AGT -532T allele due to increased MWT. This relation was observed in Slavic male offspring. It was therefore dependent on gender, age and ecogenetic context, and in addition it appeared to be modulated by the trophic effects of salt intake on LVM.

Ambulatory blood pressure and left ventricular structure and function in relation to the G-protein beta3-subunit polymorphism C825T in White Europeans.

The 825T allele of the G-protein beta(3)-subunit is associated with increased intracellular signalling. Its association with hypertension is inconsistent. We, therefore, studied the C825T polymorphism in relation to ambulatory blood pressure as well as left ventricular structure and function in two European populations. We genotyped 248 parents and 318 offspring, enrolled in the European Project on Genes in Hypertension in Cracow, Poland (n=286) and in Novosibirsk, Russian Federation (n=280). The 24-h ambulatory blood pressure was recorded using oscillometric SpaceLabs 90207 monitors. Within each centre, a single observer performed two-dimensionally guided M-mode echocardiography and Doppler sonography to measure left ventricular structure (American Society of Echocardiography conventions) and diastolic function: early (E) and late (A) peak diastolic inflow velocities. We used analysis of covariance and generalized estimating equations to allow for covariables and nonindependence among related subjects. Genotype frequencies were similar (P=0.25) in Cracow and Novosibirsk and amounted to 44.7% for CC, 47.2% for CT, and 8.1% for TT. Among parents (mean age: 51.3 years)-but not among offspring (mean age 25.1 years)-24-h, daytime and night time systolic blood pressures were 5-6 mmHg higher in TT homozygotes than in C allele carriers. In TT homozygous parents (-8.2 cm/sec, P=0.004) as well as in TT homozygous offspring (-7.5 cm/sec, P=0.02), the E-wave was significantly reduced, which in offspring also resulted in a lower E/A ratio (-0.25, P=0.002). Neither in parents nor in offspring, left ventricular mass index was associated with the C825T polymorphism. In conclusion, in TT homozygotes of both generations, early left ventricular relaxation was reduced. In TT homozygous parents, the latter observation might be because of the higher systolic pressure associated with the TT genotype.

Hemielliptic proximal isovelocity surface area method modified for clinical application: more accurate quantification of mitral regurgitation in Doppler echocardiography.

The proximal isovelocity surface area (PISA) method is one of the various methods used for quantitatively estimating mitral regurgitation. The PISA shape is hemielliptic rather than hemispheric on a slit-like orifice, and the hemielliptic method is more accurate than the hemispheric method for in vitro studies. Nevertheless, the hemispheric method is used clinically because of its simplicity, whereas the hemielliptic method is difficult to approach from 3 orthogonal directions. The present study tries to establish a modified hemielliptic method for use in clinical applications. A closed-circuit, constant flow system was designed to simulate PISA, and various types of slit-like orifices were selected. Three orthogonal PISA radii were measured and flow rates were calculated using the original hemielliptic formula from the 3 orthogonal radii. Flow rates were also calculated indirectly using a linear regression formula, and PISA radii from a bird's eye approach and lateral approaches (modified hemielliptic method) were compared. Flow rates that were determined using the original hemielliptic method correlated significantly with actual flow rates (r = 0.92, p < 0.0001; y = 1.1x - 13; SEE = 13.63 ml/s). Similarly, flow rates calculated using the modified hemielliptic method correlated significantly with actual flow rates (r = 0.90, p < 0.001; y = 0.94x - 0.78; SEE = 14.13 ml/s). The study's results imply that the modified hemielliptic method can be used to accurately quantify mitral regurgitation and could be applied for clinical examinations.

Antihypertensive treatment modulates the association between the D/I ACE gene polymorphism and left ventricular hypertrophy: a meta-analysis.

This meta-analysis attempted to derive pooled estimates for the putative association between echocardiographic or electrocardiographic left ventricular hypertrophy and the deletion/insertion (D/I) polymorphism of the angiotensin-I converting enzyme. Case-control studies were combined, using the Mantel and Haenszel approach. Joint P-values for continuous variables were calculated by Stouffer's method. Continuous measurements of left ventricular mass, which were reported in different units, were expressed on a percentage scale using the within-study mean of the II genotype as the denominator. The computerised database used for this analysis, included 28 reports with an overall sample size of 6638 subjects. The prevalence of the D allele was significantly lower in Japanese (37.2%) than in Caucasians (56.2%). A funnel plot including 12 case-control studies (4094 subjects) suggested that no publication bias was present. Overall, left ventricular hypertrophy was not associated with the D allele. Compared with the II genotype, the excess risks of left ventricular hypertrophy associated with DD and DI genotypes were only 14% (95% CI: 0.92-1.42; P = 0.23) and 5% (95% CI: 0.87-1.28; P = 0.61), respectively. However, the sensitivity analysis showed that in untreated hypertensive patients the DD genotype, compared with II homozygozity, was associated with a 192% (P = 0.002) higher risk of left ventricular hypertrophy. If left ventricular mass was analysed as a continuous trait across 23 studies (5438 subjects), overall no association with the D/I polymorphism was present. However, if untreated hypertensive patients were analysed separately, echocardiographic left ventricular mass was on average 10.1% (95% CI: 4.8-15.5%; P = 0.001) higher in DDhomozygotes than in the II reference group. Thus, in untreated hypertensive patients, in case-control studies as well as association studies, the D allele behaved as a marker for left ventricular hypertrophy. These findings support the hypothesis that the enhanced ACE activity associated with the D allele may promote left ventricular hypertrophy if a pathophysiologic process causing this disorder, remains unopposed by treatment.

Left ventricular hypertrophy in northern and Siberian populations.

Characteristics of left ventricular hypertrophy (LVH) were investigated in random samples of the Chukotka coastal Native population (131 males) and in the urban Novosibirsk population (627 males) aged 30-59. Standard epidemiological methods employing electrocardiography (EKG) and echocardiography (EchoCG) were used. The frequency of EKG-LVH in the urban population was about six percent. The prevalence of LVH in Chukotka was more than twice as high as in Novosibirsk, as determined by both EKG and EchoCG criteria. About half of EchoCG-LVH cases in Natives and one-fifth of those in the city population could not be explained by conventional reasons. Advanced family surveys in Novosibirsk established the fact that myocardial hypertrophy exhibits a family aggregation in first-degree relatives of normotensive probands affected by LVH. The data demonstrate an inherited predisposition for LVH and suggest the need for molecular-genetic analysis.

IHD in male population of Novosibirsk and Chukotka.

1. Syndrome of angina pectoris of effort is the most typical manifestation of IHD in native and newcoming population of the coastal part of Chukotka. 2. Ischemic ECG changes are less specific in relationship to IHD for Chukotka native population than in Chukotka newcoming and Novosibirsk populations.