Transgenerational and intergenerational effects of early childhood famine exposure in the cohort of offspring of Leningrad Siege survivors.

Famine exposure during early life development can affect disease risk in late-life period, yet, transmission of phenotypic features from famine-exposed individuals to the next generations has not been well characterized. The purpose of our case-control study was to investigate the association of parental starvation in the perinatal period and the period of early childhood with the phenotypic features observed in two generations of descendants of Leningrad siege survivors. We examined 54 children and 30 grandchildren of 58 besieged Leningrad residents who suffered from starvation in early childhood and prenatal age during the Second World War. Controls from the population-based national epidemiological ESSE-RF study (n = 175) were matched on sex, age and body mass index (BMI). Phenotypes of controls and descendants (both generations, children and grandchildren separately) were compared, taking into account multiple testing. Comparison of two generations descendants with corresponding control groups revealed significantly higher creatinine and lower glomerular filtration rate (GFR), both in meta-analysis and in independent analyses. The mean values of GFR for all groups were within the normal range (GFR less than 60 mL/min/1.73 m2 was recorded in 2 controls and no one in DLSS). Additionally, independent of the creatinine level, differences in the eating pattern were detected: insufficient fish and excessive red meat consumption were significantly more frequent in the children of the Leningrad siege survivors compared with controls. Blood pressure, blood lipids and glucose did not differ between the groups. Parental famine exposure in early childhood may contribute to a decrease in kidney filtration capacity and altered eating pattern in the offspring of famine-exposed individuals.

Case Report: Supernormal Vascular Aging in Leningrad Siege Survivors.

Age-related changes in the vascular system play an important role in the biological age and lifespan of a person and maybe affected from an early age onward. One of the indicators of changes in the vascular system is arterial wall stiffness and its main measure, i.e., carotid-femoral pulse wave velocity (cfPWV). We examined arterial wall stiffness in a sample of 305 Leningrad Siege survivors to assess how hunger and stressful conditions during fetal development and early childhood affected the state of the cardiovascular system at a later age and what factors may neutralize the negative impact sustained in early childhood. Here, we presented an evaluation of two unique patients with supernormal vascular aging (SUPERNOVA) phenotype from this cohort and described the details of congruence between hereditary resistance and practiced lifestyle yielding slower biological aging rate.

Simple Predictors for Cardiac Fibrosis in Patients with Type 2 Diabetes Mellitus: The Role of Circulating Biomarkers and Pulse Wave Velocity.

Cardiac fibrosis is the basis of structural and functional disorders in patients with diabetes mellitus (T2DM). A wide range of laboratory and instrumental methods is used for its prediction. The study aimed to identify simple predictors of cardiac fibrosis in patients with T2DM based on the analysis of circulating fibrosis biomarkers and arterial stiffness. The study included patients with T2DM (n = 37) and cardiovascular risk factors (RF, n = 27) who underwent ECHO, cardiac magnetic resonance imaging (MRI), pulse wave analysis (PWV), reactive hyperemia (RH), peripheral arterial tonometry, carotid ultrasonography, and assessment of serum fibrosis biomarkers. As a control group, 15 healthy subjects were examined. Left ventricular concentric hypertrophy was accompanied by an increased serum galectin-3 level in T2DM patients. There was a relationship between the PICP and HbA1c levels in both main groups (R2 = 0.309; p = 0.014). A negative correlation between PICP level and the global longitudinal strain (GLS) was found (r = −0.467; p = 0.004). The RH index had a negative correlation with the duration of diabetes (r = −0.356; p = 0.03), the carotid-femoral PWV (r = −0.371; p = 0.024), and the carotid intima-media thickness (r = −0.622; p < 0.001). The late gadolinium-enhanced (LGE) cardiac MRI was detected in 22 (59.5%) T2DM and in 4 (14.85%) RF patients. Diabetes, its baseline treatment with metformin, HbA1c and serum TIMP-1 levels, and left ventricle hypertrophy had moderate positive correlations with LGE findings (p < 0.05). Using the multivariate regression analysis, increased TIMP-1 level was identified as an independent factor associated with cardiac fibrosis.

Proprioceptive sensitivity to imposed finger deflections.

Hand proprioception, the sense of the posture and movements of the wrist and digits, is critical to dexterous manual behavior and to stereognosis, the ability to sense the three-dimensional structure of objects held in the hand. To better understand this sensory modality and its role in hand function, we sought to characterize the acuity with which the postures and movements of finger joints are sensed. To this end, we measured the ability of human subjects to discriminate changes in posture and speed around the three joints of the index finger. In these experiments, we isolated the sensory component by imposing the postures on an otherwise still hand, to complement other studies in which subjects made judgments on actively achieved postures. We found that subjects could reliably sense 12-16% changes in joint angle and 18-32% changes in joint speed. Furthermore, the acuity for posture and speed was comparable across the three joints of the finger. Finally, task performance was unaffected by the presence of a vibratory stimulus, calling into question the role of cutaneous cues in hand proprioception.NEW & NOTEWORTHY Manual dexterity and stereognosis are supported by two exquisite sensory systems, namely touch and proprioception. Here, we measure the sensitivity of hand proprioception and show that humans can sense the posture and movements of the fingers with great accuracy. We also show that application of a skin vibration does not impair sensitivity, suggesting that proprioceptive acuity relies primarily on receptors in the muscles (and possibly tendons) rather than the skin.

Physical Activity Is Associated With Sleep Quality: Results of the ESSE-RF Epidemiological Study.

BACKGROUND AND HYPOTHESIS: Physical activity (PA) is an important behavioral factor associated with the quality of life and healthy longevity. We hypothesize that extremely low and extremely high levels of daily PA (including occupational PA) may have a negative impact on sleep quality and psychological well-being. OBJECTIVE: The aim of the study is to investigate the association between the level and type of PA and sleep problems in adult population. MATERIALS AND METHODS: The sample of the study consisted of the participants from the population-based cohort of The Epidemiology of Cardiovascular Risk Factors and Diseases in Regions of the Russian Federation Study (ESSE-RF). The data of three regions (Saint Petersburg, Samara, Orenburg), varying in geographic, climatic, socioeconomic characteristics, was included into analysis. The total sample consisted of 4,800 participants (1,600 from each region; 1,926 males, 2,874 females), aged 25-64. The level of PA was evaluated using three parameters: the type of PA at work, the frequency of an intensive/high PA including sport (times a week), the mean duration of leisure-time walking (minutes a day). The measures of sleep quality were sleep duration and the frequency of difficulty falling asleep, difficulty maintaining sleep, daytime sleepiness, and sleep medication use. PA and sleep characteristics were assessed by interview carried by the trained medical staff. RESULTS: When controlling for gender, age and socioeconomic status (SES) extremely high occupational PA was a significant risk factor for difficulty falling asleep three or more times a week [OR(CI95%) = 1.9(1.2-3.0), p = 0.003] while working in a sitting position or having moderate physical load at work were not associated with sleep characteristics. Having a high physical load six or more times a week was a risk factor for difficulty falling asleep controlling for gender, age and SES [OR(CI95%) = 1.9(1.4-3.4), p = 0.001]. The association between leisure-time walking and sleep characteristics was insignificant. Walking less than an hour a day was associated with increased depression scores (46.5 vs. 41.9%, p = 0.006). CONCLUSION: High physical load at work and excessively frequent intensive PA are associated with difficulties initiating sleep and may represent a risk factor for insomnia.

Pulse wave velocity is decreased in acromegaly compared to non-acromegaly study participants with similar cardiovascular risk profile.

OBJECTIVE: Acromegaly patients were reported to have an increased arterial stiffness that could contribute to the frequent cardiovascular complications in this population. The chronic excess of GH and IGF-1 may lead to arterial stiffening via different mechanisms, including hypertension, impaired glucose tolerance and dyslipidemia, however, it is not known whether the activation of GH/IGF-1 axis might influence arterial stiffening independently of cardiovascular risk factors. The objective of this prospective case-control study was to compare arterial stiffness assessed with pulse-wave velocity (PWV) in acromegaly versus non-acromegaly group with similar cardiovascular risk profile. DESIGN: This prospective case-control study included 27 patients with active acromegaly, who underwent the assessment of clinical, physiological, biochemical parameters and the evaluation of PWV with applanation tonometry. We used "The epidemiology of cardiovascular disease in different regions of the Russian Federation" study database (n = 522) to establish a non-acromegaly control group with similar cardiovascular risk profile (n = 54). Non-acromegaly control participants underwent the same assessment as acromegaly patients except for the measurement of serum GH and IGF-1 levels. We compared PWV in acromegaly patients to the general non-acromegaly cohort and its subset, matched with acromegaly patients for cardiovascular risk factors. We also investigated the associations of PWV with clinical, physiological and biochemical parameters in acromegaly and non-acromegaly group using correlation and regression analysis with adjustment for age and sex. RESULTS: Acromegaly patients had lower PWV (6.70 (5.75-7.65) m/s) compared to unmatched non-acromegaly control cohort (7.50 (6.70-8.57) m/s, p = 0.01) and to the non-acromegaly control group matched for cardiovascular risk factors (7.45 (6.73-8.60), p < 0.01). In non-acromegaly control group PWV was associated with BMI (ρ = 0.40, p < 0.01; ß = 0.09, p < 0.01), obesity (r = 0.46, p < 0.01; ß = 1.36, p < 0.01), systolic blood pressure (ρ = 0.60, p < 0.01; ß = 0.05, p < 0.01), diastolic blood pressure (ρ = 0.62, p < 0.01; ß = 0.07, p < 0.01), triglycerides (ρ = 0.55, p < 0.01; ß = 0.58, p = 0.04), glucose (ρ = 0.54, p < 0.01; ß = 0.70, p < 0.01) and diabetes (r = 0.40, p < 0.01; ß = 1.10, p = 0.03), while in acromegaly group PWV was associated with IGF-1 expressed in mcg/ml (ρ = -0.49, p ≤0.01; ß = -0.002, p ≤0.01) and in percentage of the upper limit of the normal (ρ = -0.47, p = 0.01; ß = -0.005, p ≤0.01) as well as with diuretics treatment (ß = -1.17, p = 0.03). CONCLUSIONS: PWV is decreased in acromegaly patients compared to non-acromegaly control participants with similar cardiovascular risk profile. Future studies need to explore the role of GH/IGF-1 axis in the regulation of arterial wall properties and the reliability of PWV as a prognostic marker of cardiovascular complications in acromegaly.

Sleep Duration, Lipid Profile and Insulin Resistance: Potential Role of Lipoprotein(a).

Lipoprotein (a) (Lp(a)) is considered a genetic factor for cardiovascular disease playing an important role in atherogenesis and thrombosis, but the evidence about its association with sleep duration is controversial. We evaluated the relation between self-reported sleep duration and Lp(a). Among 1600 participants of the population-based sample, we selected 1427 subjects without previously known cardiovascular events, who answered the questions about their sleep duration; had valid lipid profile results (total cholesterol, low- and high-density lipoproteins, Lp(a), apolipoprotein AI (ApoAI), ApoB, and ApoB/ApoAI); and did not take lipid-lowering drugs (mean age 46 ± 12 years). We performed a structured interview, which included questions about lifestyle, medical history, complaints, and sleep duration (How long have you been sleeping per night during the last month?). Sleep duration was classified as follows: <6 h/night-short, 6-9 h/night-normal, and ≥10 h/night-long. Overall, 73 respondents (5.2%) were short-sleepers and 69 (4.8%) long-sleepers. Males were slightly more prevalent among short-sleepers. The groups matched by age, body mass index, blood pressure, diabetes mellitus, and hypertension rate. Short-sleepers had lower rates of high total cholesterol (≥5.0 mmol/L), lower Lp(a) levels and lower rates of increased Lp(a) ≥0.5 g/L, and higher insulin and insulin resistance (assessed by the homeostatic model assessment for insulin resistance (HOMA-IR)). ApoAI, ApoB, their ratio, and other lab tests were similar in the groups. The multinomial logistic regression demonstrated that only the short sleep duration was independently (odds ratio (OR) 0.29, 95% confidence interval (CI) (0.09-0.91), p = 0.033) associated with Lp(a) (χ2 = 41.58, p = 0.003). Other influencing factors were smoking and HOMA-IR. Such an association was not found for long-sleepers. In conclusion, a short-sleep duration is associated with Lp(a). The latter might mediate the higher insulin resistance and higher cardiometabolic risks in short-sleepers.

Finger Posture and Finger Load are Perceived Independently.

The ability to track the time-varying postures of our hands and the forces they exert plays a key role in our ability to dexterously interact with objects. However, how precisely and accurately we sense hand kinematics and kinetics has not been completely characterized. Furthermore, the dominant source of information about hand postures stems from muscle spindles, whose responses can also signal isometric force and are modulated by fusimotor input. As such, one might expect that changing the state of the muscles - for example, by applying a load - would influence perceived finger posture. To address these questions, we measure the acuity of human hand proprioception, investigate the interplay between kinematic and kinetic signals, and determine the extent to which actively and passively achieved postures are perceived differently. We find that angle and torque perception are highly precise; that loads imposed on the finger do not affect perceived joint angle; that joint angle does not affect perceived load; and that hand postures are perceived similarly whether they are achieved actively or passively. The independence of finger posture and load perception contrasts with their interdependence in the upper arm, likely reflecting the special functional importance of the hand.

Epidemiology of cardiovascular risk factors in two population-based studies.

We aimed to compare cardiovascular risk factors prevalence in Italy and Russia through cross-sectional database analysis. The study has been based on data from ESSE-RF and from baseline of PLIC study, two population-based epidemiological studies aimed to investigate prevalence of risk factors and evaluating contribution of traditional and new risk factors into morbidity and cardiovascular mortality. A total of 2203 patients with left and right intima-media thickness (IMT) measurements constituted the source population (1205 from PLIC study and 998 from ESSE-RF study). Sample of ESSE-RF study had slightly more diabetic and hypertensive individuals, while the percentage of subjects with high cholesterol value was lower than in the other sample (67.1% vs 79.9%). The median LDL-C value was higher among individuals not treated with statins in the PLIC sample (p < 0.001), while was comparable among subjects receiving statin therapy. On the other hand, the percentage of individuals with positive cardiovascular history was higher in ESSE-RF sample. This could also explain the higher mean IMT value (0.71 ±â€¯0.17 vs 0.63 ±â€¯0.13) in the whole sample, and among patients without past cardiovascular events (regardless of statin treatment), despite some differences in major risk factors. Despite Russian and Italian populations are culturally and geographically different, they are not so different based on characteristics analyzed.

Subclinical target organ damage in subjects with different components of metabolic syndrome.

BACKGROUND: To assess the association of metabolic syndrome (MS) and its components with target organ damage in a follow-up study of relatively healthy bank employers. METHODS: Out of 1600 random samples of office workers in Saint Petersburg (Russia), a group of 383 participants with at least one component of MS and without cardiovascular complications was selected (mean age 46.6 ± 9.0 years, 214 females (64.6%)). Follow-up visit was performed in 331 subjects. Target organ damage (TOD) was assessed by echocardiography, carotid ultrasound, applanational tonometry, brachial-ankle index, and urine albumin excretion measurements. Anthropometry, vital signs, and biochemistry were performed according to standard protocols. RESULTS: Presence of MS was not associated with higher probability of TOD. Multiple linear regression revealed significant association of all markers of TOD with older age. Hypertension was a significant predictor of left ventricular hypertrophy (LVH), increased arterial stiffness, and early signs of carotid atherosclerosis in logistic regression adjusted for age and gender. During follow-up, proportion of patients with LVH significantly decreased (from 46.7% to 32.9%, р = 0.003) and prevalence of patients with IMT > 0.09 сm increased (from 24.5% to 44.1%, p < 0.001) accompanying by significant declining of office blood pressure (BP) and total cholesterol. CONCLUSIONS: MS per se is not related to increased probability to TOD. Hypertension, female gender, and older age are main determinants of subclinical changes. After 2-years follow-up, significant LVH and renal damage regression was observed probably owing to BP reduction. Alternatively, early signs of carotid atherosclerosis increase with aging despite decreasing of the prevalence of hypercholesterolemia.

Metabolically healthy obese and metabolically unhealthy non-obese phenotypes in a Russian population.

INTRODUCTION: The aim of the study was to estimate the prevalence of metabolically healthy obese (MHO) and metabolically unhealthy non-obese (MUNO) phenotypes in Russian population. DESIGN AND METHODS: In cross-sectional epidemiology survey "Epidemiology of cardiovascular diseases and its risk factors in some regions of the Russian Federation" a random sampling of 21,121 subjects (25-65 years), stratified by age and sex was involved. Anthropometry, blood pressure (BP) measurement and fasting blood-tests (glucose, lipids) were performed according to standard protocols. Criteria for MHO-body mass index (BMI) ≥30 kg/m2 and ≤2 of markers: HDL < 1.30 (females)/1.04 (males) mmol/l; triglycerides ≥1.7 mmol/l; glucose ≥5.6 mmol/l or treatment; waist >88 (females)/102 (males) cm and BP ≥ 130/85 mm Hg or therapy. Criteria for MUNO was BMI < 30 kg/m2 and ≥2 markers listed above. Simple tabulations, descriptive statistics, post-stratification weights and logistic regression were used for analyses. RESULTS: MHO phenotype was detected in 2856 (41.5%) obese people; MUNO phenotype-in 4762 (34.4%) non-obese subjects. Aging was negatively associated with MHO and positively with MUNO prevalence. Gender was registered as determinant only of MUNO probability. No dramatic differences in lifestyle risk factors between 3 BMI groups (lean, overweight, obese) were found out. CONCLUSION: Half of obese Russian inhabitants are metabolically healthy. At the same time, metabolic abnormalities were detected in one third of non-obese participants with a shift to male gender.

Siege of Leningrad Survivors Phenotyping and Biospecimen Collection.

BACKGROUND: Poor nutrition during the early stages of human development can lead to rare pathological conditions in adult life. The best-known and most severe historical cases of famine include the Dutch 'Hunger Winter,' the Finnish famine, the Chinese Great famine, and the siege of Leningrad. The siege of Leningrad (now Saint Petersburg) was one of the longest in history, lasting 872 days, from September 8, 1941 to January 27, 1944. There were 670,000 registered deaths of the civil population, in which 97% died due to starvation. The aim of the present study is to create a collection of biospecimens from extensively phenotyped siege of Leningrad survivors, who underwent starvation during the early periods of their lives, and from a matched control group. METHODS: A total 305 siege survivors and 51 age- and sex- matched control subjects were investigated in of an observational retroprospective cohort study in 2009-2011 at a baseline visit. After 3 years of follow-up, 252 siege survivors (182 females and 70 males; mean age 74.7 ± 2.6 years) and 45 controls (32 females and 13 males; mean age 75.5 ± 2.8 years) were examined. All siege survivors were exposed to the extreme dietary restriction and stress associated with the siege in their early childhood. All participants signed informed consent and were subject to questionnaires and physical examination, as well as various laboratory and instrumental tests. Anthropometry, blood measurement, cognitive and physiological testing, and vascular damage assessment were performed. RESULTS: Blood specimens of the extensively phenotyped siege survivors were collected and processed (blood plasma, blood serum, and flash-frozen PBMC); serum and urine were used for laboratory tests. CONCLUSIONS: We believe that data obtained from this unique collection of biospecimens can elucidate the mechanisms of healthy aging and emphasize the importance of reproductive health, counseling, and monitoring among people with eating disorders.

Seventy years after the siege of Leningrad: does early life famine still affect cardiovascular risk and aging?

OBJECTIVE: To assess the cardiovascular health, markers of cardiovascular aging and telomere length in survivors of the siege of Leningrad, who were either born during the siege or lived in the besieged city in their early childhood. METHODS: Survivors of the Leningrad siege (n = 305, 64-81 years) and a control group of age and sex-matched individuals (n = 51, 67-82 years) were examined in terms of a observational retrospective cohort study. All participants were interviewed regarding risk factors, cardiovascular diseases, and therapy. Blood pressure measurement, anthropometry, echocardiography, and electrocardiography were performed according to standard guidelines. Fasting lipids and glucose were measured. Relative telomere length was measured by quantitative PCR, and the ratio of telomere repeat copy number to single gene copy number (T/S) was calculated for each DNA sample. RESULTS: Survivors had lower anthropometric parameters (height, weight, and BMI) and higher high-density lipoprotein level. There were no significant differences in the prevalence of cardiovascular diseases and target organ damage between groups. However, survivors had shorter telomere length: T/S ratio 0.44 (0.25; 0.64) vs. controls 0.91 (0.47; 1.13) (P < 0.0001), both in men and women, with clear association with the period of famine in early life. Exposure to famine in childhood and intrauterine period of life was associated with a higher prevalence of hypertension and shorter telomere length. CONCLUSION: Early-life famine, especially started in the intrauterine period and late childhood, may contribute to accelerated aging with telomere shortening in both sexes, but has no direct effect on the prevalence of cardiovascular diseases and risk factors after seven decades since exposure.