Long-term glycemic variability and risk of adverse outcomes: a systematic review and meta-analysis

OBJECTIVE: Glycemic variability is emerging as a measure of glycemic control, which may be a reliable predictor of complications. This systematic review and meta-analysis evaluates the association between HbA1c variability and micro- and macrovascular complications and mortality in type 1 and type 2 diabetes. RESEARCH DESIGN AND METHODS: Medline and Embase were searched (2004–2015) for studies describing associations between HbA1c variability and adverse outcomes in patients with type 1 and type 2 diabetes. Data extraction was performed independently by two reviewers. Random-effects meta-analysis was performed with stratification according to the measure of HbA1c variability, method of analysis, and diabetes type. RESULTS: Seven studies evaluated HbA1c variability among patients with type 1 diabetes and showed an association of HbA1c variability with renal disease (risk ratio 1.56 [95% CI 1.08–2.25], two studies), cardiovascular events (1.98 [1.39–2.82]), and retinopathy (2.11 [1.54–2.89]). Thirteen studies evaluated HbA1c variability among patients with type 2 diabetes. Higher HbA1c variability was associated with higher risk of renal disease (1.34 [1.15–1.57], two studies), macrovascular events (1.21 [1.06–1.38]), ulceration/gangrene (1.50 [1.06–2.12]), cardiovascular disease (1.27 [1.15–1.40]), and mortality (1.34 [1.18–1.53]). Most studies were retrospective with lack of adjustment for potential confounders, and inconsistency existed in the definition of HbA1c variability. CONCLUSIONS: HbA1c variability was positively associated with micro- and macrovascular complications and mortality independently of the HbA1c level and might play a future role in clinical risk assessment

Blood pressure variability and cardiovascular risk in the PROspective study of pravastatin in the elderly at risk (PROSPER)

Variability in blood pressure predicts cardiovascular disease in young- and middle-aged subjects, but relevant data for older individuals are sparse. We analysed data from the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) study of 5804 participants aged 70–82 years with a history of, or risk factors for cardiovascular disease. Visit-to-visit variability in blood pressure (standard deviation) was determined using a minimum of five measurements over 1 year; an inception cohort of 4819 subjects had subsequent in-trial 3 years follow-up; longer-term follow-up (mean 7.1 years) was available for 1808 subjects. Higher systolic blood pressure variability independently predicted long-term follow-up vascular and total mortality (hazard ratio per 5 mmHg increase in standard deviation of systolic blood pressure = 1.2, 95% confidence interval 1.1–1.4; hazard ratio 1.1, 95% confidence interval 1.1–1.2, respectively). Variability in diastolic blood pressure associated with increased risk for coronary events (hazard ratio 1.5, 95% confidence interval 1.2–1.8 for each 5 mmHg increase), heart failure hospitalisation (hazard ratio 1.4, 95% confidence interval 1.1–1.8) and vascular (hazard ratio 1.4, 95% confidence interval 1.1–1.7) and total mortality (hazard ratio 1.3, 95% confidence interval 1.1–1.5), all in long-term follow-up. Pulse pressure variability was associated with increased stroke risk (hazard ratio 1.2, 95% confidence interval 1.0–1.4 for each 5 mmHg increase), vascular mortality (hazard ratio 1.2, 95% confidence interval 1.0–1.3) and total mortality (hazard ratio 1.1, 95% confidence interval 1.0–1.2), all in long-term follow-up. All associations were independent of respective mean blood pressure levels, age, gender, in-trial treatment group (pravastatin or placebo) and prior vascular disease and cardiovascular disease risk factors. Our observations suggest variability in diastolic blood pressure is more strongly associated with vascular or total mortality than is systolic pressure variability in older high-risk subjects

Epigenomes in Cardiovascular Disease.

If unifying principles could be revealed for how the same genome encodes different eukaryotic cells and for how genetic variability and environmental input are integrated to impact cardiovascular health, grand challenges in basic cell biology and translational medicine may succumb to experimental dissection. A rich body of work in model systems has implicated chromatin-modifying enzymes, DNA methylation, noncoding RNAs, and other transcriptome-shaping factors in adult health and in the development, progression, and mitigation of cardiovascular disease. Meanwhile, deployment of epigenomic tools, powered by next-generation sequencing technologies in cardiovascular models and human populations, has enabled description of epigenomic landscapes underpinning cellular function in the cardiovascular system. This essay aims to unpack the conceptual framework in which epigenomes are studied and to stimulate discussion on how principles of chromatin function may inform investigations of cardiovascular disease and the development of new therapies

Cardiovascular Consequences of Unfair Pay

This paper investigates physiological responses to perceptions of unfair pay. In a simple principal agent experiment agents produce revenue by working on a tedious task. Principals decide how this revenue is allocated between themselves and their agents. In this environment unfairness can arise if an agent's reward expectation is not met. Throughout the experiment we record agents' heart rate variability. Our findings provide evidence of a link between perceived unfairness and heart rate variability. The latter is an indicator of stress-related impaired cardiac autonomic control, which has been shown to predict coronary heart diseases in the long run. Establishing a causal link between unfair pay and heart rate variability therefore uncovers a mechanism of how perceptions of unfairness can adversely affect cardiovascular health. We further test potential adverse health effects of unfair pay using data from a large representative data set. Complementary to our experimental findings we find a strong and highly significant association between health outcomes, in particular cardiovascular health, and fairness of pay.fairness, social preferences, inequality, heart rate variability, health, experiments, SOEP

Visit-to-visit blood pressure variability and cardiovascular and kidney diseases

In healthy people and patients with hypertension, blood pressure varies between clinic visits every several days, a week, or a month apart. Although long thought to be an artifact, recent data suggest that visit-to-visit variability of blood pressure is reproducible and has independent association with cardiovascular outcomes and mortality. There currently is no consensus on how to define blood pressure variability best. The most common metric used is standard deviation of mean blood pressure, variation independent of the mean and average real variability. Blood pressure variability is higher in female, older age and patients with hypertension, with cardiovascular diseases, with diabetes mellitus and chronic kidney disease. Therefore, we are not sure if higher blood pressure variability is the only marker of arterial stiffness and consequence of end organ damage or prognostic indicator of cardiovascular events. We also do not know whether reducing blood pressure variability would reduce the risk of cardiovascular outcomes. However, the number of studies on blood pressure variability is growing exponentially and perhaps in the near future, high blood pressure variability will also be the goal of hypertension therapy.In healthy people and patients with hypertension, blood pressure varies between clinic visits every several days, a week, or a month apart. Although long thought to be an artifact, recent data suggest that visit-to-visit variability of blood pressure is reproducible and has independent association with cardiovascular outcomes and mortality. There currently is no consensus on how to define blood pressure variability best. The most common metric used is standard deviation of mean blood pressure, variation independent of the mean and average real variability. Blood pressure variability is higher in female, older age and patients with hypertension, with cardiovascular diseases, with diabetes mellitus and chronic kidney disease. Therefore, we are not sure if higher blood pressure variability is the only marker of arterial stiffness and consequence of end organ damage or prognostic indicator of cardiovascular events. We also do not know whether reducing blood pressure variability would reduce the risk of cardiovascular outcomes. However, the number of studies on blood pressure variability is growing exponentially and perhaps in the near future, high blood pressure variability will also be the goal of hypertension therapy

Cardiovascular autonomic neuropathy among non- insulin dependent diabetics patients

Background and Objective: Cardiovascular autonomic neuropathy (CAN) is the most common and important type of diabetic autonomic neuropathy. Silent myocardial infarction, respiratory failure and increased mortality are the outcomes of CAN. This study was carried out to screen the cardiovascular autonomic neuropathy in non- insulin dependent diabetics patients. Method: This descriptive - analytic study was carried on 70 (22 males, 48 females) non- insulin dependent diabetics’ patients. Resting heart rate, heart rate variability, orthostatic changes in heart rate, blood pressure and corrected QT interval were recorded for each subject. The final findings were categorized as follow: 0=normal, 1=borderline and 2=CAN positive. Results: 10 (14.3%) of patients were normal, 35 (50%) of patients were borderline and 25 (35.7%) of patients were considered cardiovascular autonomic neuropathy positive. There was significant differences between duration of diabetes and three CAN scores (P<0.05). The systolic blood pressure alterations showed the maximum correlation with CAN scores (r=0.509). Conclusion: In our study, the rate of cardiovascular autonomic neuropathy was higher than other reports. The most important risk factor for cardiovascular autonomic neuropathy was more than 10 years history of diabetes mellitus. Keywords: Diabetes mellitus, Cardiovascular autonomic neuropathy, Hypertensio

Naturalistic monitoring of the affect-heart rate relationship: A Day Reconstruction Study

Objective: Prospective studies have linked both negative affective states and trait neuroticism with hypertension, cardiovascular disease, and mortality. However, identifying how fluctuations in cardiovascular activity in day-to-day settings are related to changes in affect and stable personality characteristics has remained a methodological and logistical challenge. Design - In the present study, we tested the association between affect, affect variability, personality and heart rate (HR) in daily life. Measures: We utilized an online day reconstruction survey to produce a continuous account of affect, interaction, and activity patterns during waking hours. Ambulatory HR was assessed during the same period. Consumption, activity, and baseline physiological characteristics were assessed in order to isolate the relationships between affect, personality and heart rate. Results: Negative affect and variability in positive affect predicted an elevated ambulatory HR and tiredness a lower HR. Emotional stability was inversely related to HR, whereas agreeableness predicted a higher HR. Baseline resting HR was unrelated to either affect or personality. Conclusion: The results suggest that both state and trait factors implicated in negative affectivity may be risk factors for increased cardiovascular reactivity in everyday life. Combining day reconstruction with psychophysiological and environmental monitoring is discussed as a minimally invasive method with promising interdisciplinary relevance.heart rate, negative affect, affect variability, Big Five, Day Reconstruction Method

The relationship between glycaemic variability and cardiovascular autonomic dysfunction in patients with type 1 diabetes : a systematic review

Rigorous glycaemic control-reflected by low HbA1c goals-is of the utmost importance in the prevention and management of complications in patients with type 1 diabetes mellitus (T1DM). However, previous studies suggested that short-term glycaemic variability (GV) is also important to consider as excessive glucose fluctuations may have an additional impact on the development of diabetic complications. The potential relationship between GV and the risk of cardiovascular autonomic neuropathy (CAN), a clinical expression of cardiovascular autonomic dysfunction, is of increasing interest. This systematic review aimed to summarize existing evidence concerning the relationship between GV and cardiovascular autonomic dysfunction in T1DM. An electronic database search of Medline (PubMed), Web of Science and Embase was performed up to October 2019. There were no limits concerning year of publication. Methodological quality was evaluated using the Newcastle Ottawa Scale for observational studies. Six studies (four cross-sectional and two prospective cohorts) were included. Methodological quality of the studies varied from level C to A2. Two studies examined the association between GV and heart rate variability (HRV), and both found significant negative correlations. Regarding cardiovascular autonomic reflex tests (CARTs), two studies did not, while two other studies did find significant associations between GV parameters and CART scores. However, associations were attenuated after adjusting for covariates such as HbA1c, age and disease duration. In conclusion, this systematic review found some preliminary evidence supporting an association between GV and cardiovascular autonomic dysfunction in T1DM. Hence, uncertainty remains whether high GV can independently contribute to the onset or progression of CAN. The heterogeneity in the methodological approach made it difficult to compare different studies. Future studies should therefore use uniformly evaluated continuous glucose monitoring-derived parameters of GV, while standardized assessment of HRV, CARTs and other potential cardiac autonomic function parameters is needed for an unambiguous definition of CAN

Cardiovascular Consequences of Unfair Pay

This paper investigates physiological responses to perceptions of unfair pay. In a simple principal agent experiment agents produce revenue by working on a tedious task. Principals decide how this revenue is allocated between themselves and their agents. In this environment unfairness can arise if an agent's reward expectation is not met. Throughout the experiment we record agents' heart rate variability. Our findings provide evidence of a link between perceived unfairness and heart rate variability.The latter is an indicator of stressrelated impaired cardiac autonomic control, which has been shown to predict coronary heart diseases in the long run. Establishing a causal link between unfair pay and heart rate variability therefore uncovers a mechanism of how perceptions of unfairness can adversely affect cardiovascular health. Wefurther test potential adverse health effects of unfair pay using data from a large representative data set. Complementary to our experimental findings we find a strong and highly significant association between health outcomes, in particular cardiovascular health, and fairness of pay.Fairness, social preferences, inequality, heart rate variability, health, experiments, SOEP