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Biomedical subjects

Virend K Somers

Publications and source records attributed to Virend K Somers.

At least 19 recordsLinked to original sources

Tonic chemoreflex activation contributes to the elevated muscle sympathetic nerve activity in patients with chronic renal failure.

OBJECTIVE: Sympathetic activation may contribute to both cardiovascular morbidity and the progression of chronic kidney disease. The role of the chemoreceptors in determining sympathetic nerve discharge in patients with chronic renal failure (CRF) is unknown. We tested the hypothesis that tonic activation of excitatory chemoreceptor afferents contributes to the elevated sympathetic activity in patients with CRF. METHODS: Utilizing a double-blind, randomized, vehicle-controlled design, we examined the effects of chemoreflex deactivation on muscle sympathetic nerve activity (MSNA). We compared effects of breathing 100% oxygen for 15 min with effects of breathing room air for 15 min in 12 stable patients with CRF and in 12 control individuals with similar age, gender, blood pressure and body mass index. RESULTS: The baseline MSNA was elevated significantly in the patients with CRF as compared with the control individuals (50 +/- 2 vs 42 +/- 2 bursts/min; P < 0.05). Reductions in systolic blood pressure and pulse pressure in response to the administration of 100% oxygen were significantly different from those observed during administration of room air in patients with CRF. In patients with CRF, MSNA decreased by 29 +/- 7% (P < 0.01) during hyperoxia but did not change during administration of room air (5 +/- 6%; P = NS). By contrast, neither 100% oxygen or room air changed any measures in control individuals. CONCLUSIONS: Tonic activation of excitatory chemoreflex afferents contributes to increased efferent sympathetic activity to muscle circulation and to blood pressure control in patients with CRF. These findings may have important implications for understanding mechanisms underlying the link between CRF and cardiovascular disease.

Administration, Inhalation↗

Familial premature coronary artery disease mortality and obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea (OSA) is linked to both coronary artery disease (CAD) and sudden death, but any causal role remains unclear. A family history of premature CAD and related mortality is an independent risk factor for the development of CAD. We hypothesized that OSA is associated with a family history of premature mortality from ischemic heart disease. METHODS: We prospectively studied 588 subjects who underwent polysomnography from May 2000 to June 2004. Demographics, comorbidities, family history of cardiovascular disease, and the ages and causes of death for 10 strata of family members were recorded for all subjects. We excluded those subjects with known causes of premature cardiac death, such as hypertrophic cardiomyopathy and long-QT syndrome. OSA was defined by American Academy of Sleep Medicine criteria (ie, apnea-hypopnea index >or= 5). Premature CAD mortality was defined as death due to ischemic heart disease or sudden cardiac death before 55 years of age (men) or 65 years of age (women). RESULTS: Polysomnography confirmed OSA in 316 subjects and excluded it in 202 subjects. The unadjusted odds ratio (OR) for OSA and a family history of premature CAD mortality was 2.11 (95% confidence interval [CI], 1.10 to 4.31; p = 0.031). After adjusting for each subject's sex, body mass index, and history of CAD, there was a significant and independent association between OSA and family history of premature CAD mortality (OR, 2.13; 95% CI, 1.04 to 4.66; p = 0.046). CONCLUSIONS: Regardless of their own CAD status, people with OSA are more likely than those without OSA to have a family history of premature CAD mortality.

Cause of Death↗

Association between plasma adiponectin levels and unstable coronary syndromes.

AIMS: Obesity is a risk factor for an acute coronary syndrome (ACS). The association between elevated body mass index (BMI) and ACS is independent of most traditional risk factors, suggesting a possible contribution of other body fat-related mediators. This study evaluated the association between adiponectin and ACS. METHODS AND RESULTS: Four hundred and ninety-nine patients undergoing coronary angiography were divided into a subgroup without (n = 331) and with ACS (n = 168). In multiple regression analysis, higher adiponectin levels were independently associated with a lower risk of ACS [odds ratio (OR) = 0.61; 95% CIs: 0.46-0.81; P < 0.001]. In contrast, a higher BMI, a history of myocardial infarction, C-reactive protein, and angiographic coronary artery disease severity were all associated with a higher risk. The greatest increase in risk for ACS was seen at adiponectin levels < or = 5.5 microg/mL. CONCLUSION: Higher plasma adiponectin levels are independently associated with a lower risk of ACS.

Acute Coronary Syndrome↗

Sleep and the metabolic syndrome.

The metabolic syndrome represents a clustering of several interrelated risk factors of metabolic origin that are thought to increase cardiovascular risk. It is still uncertain whether this clustering results from multiple underlying risk factors or whether it has a single cause. One metabolic abnormality that may underlie several clinical characteristics of the metabolic syndrome is insulin resistance. This review discusses the evidence that sleep disturbances (obstructive sleep apnoea, sleep deprivation and shift work) may independently lead to the development of both insulin resistance and individual clinical components of the metabolic syndrome. The converse may also be true, in that metabolic abnormalities associated with the metabolic syndrome and insulin resistance may potentially exacerbate sleep disorders. The notion that sleep disturbances exert detrimental metabolic effects may help explain the increasing prevalence of the metabolic syndrome and insulin resistance in the general population and may have important implications for population-based approaches to combat the increasing epidemic of metabolic and cardiovascular disease.

Animals↗

Association of bodyweight with total mortality and with cardiovascular events in coronary artery disease: a systematic review of cohort studies.

BACKGROUND: Studies of the association between obesity, and total mortality and cardiovascular events in patients with coronary artery disease (CAD) have shown contradictory results. We undertook a systematic review to determine the extent and nature of this association. METHODS: We selected cohort studies that provided risk estimates for total mortality, with or without cardiovascular events, on the basis of bodyweight or obesity measures in patients with CAD, and with at least 6 months' follow-up. CAD was defined as history of percutaneous coronary intervention, coronary artery bypass graft, or myocardial infarction. We obtained risk estimates for five predetermined bodyweight groups: low, normal weight (reference), overweight, obese, and severely obese. FINDINGS: We found 40 studies with 250,152 patients that had a mean follow-up of 3.8 years. Patients with a low body-mass index (BMI) (ie, <20) had an increased relative risk (RR) for total mortality (RR=1.37 [95% CI 1.32-1.43), and cardiovascular mortality (1.45 [1.16-1.81]), overweight (BMI 25-29.9) had the lowest risk for total mortality (0.87 [0.81-0.94]) and cardiovascular mortality (0.88 [0.75-1.02]) compared with those for people with a normal BMI. Obese patients (BMI 30-35) had no increased risk for total mortality (0.93 [0.85-1.03]) or cardiovascular mortality (0.97 [0.82-1.15]). Patients with severe obesity (> or =35) did not have increased total mortality (1.10 [0.87-1.41]) but they had the highest risk for cardiovascular mortality (1.88 [1.05-3.34]). INTERPRETATION: The better outcomes for cardiovascular and total mortality seen in the overweight and mildly obese groups could not be explained by adjustment for confounding factors. These findings could be explained by the lack of discriminatory power of BMI to differentiate between body fat and lean mass.

Angioplasty, Balloon, Coronary↗

The effect of patient sex on recurrence of atrial fibrillation following successful direct current cardioversion.

BACKGROUND: The effect of patient sex on recurrence of atrial fibrillation after a successful direct current cardioversion is unknown. METHODS: This prospective study included 773 patients (486 [63%] men and 287 [37%] women) undergoing successful direct current cardioversion of atrial fibrillation between May 2000 and July 2003. Patient characteristics at presentation were recorded. The primary end point was the time between cardioversion and the first documented recurrence of arrhythmia. RESULTS: At presentation, women were older and had a higher prevalence of hypertension and valvular disease compared with men. In addition, women had worse mechanical left atrial appendage function. Arrhythmia recurrence was more prevalent in women (50.0% at 1 year compared with 43.4% in men, and 75.8% at 2 years compared with 67.0% in men; P = .03). On the basis of multivariate analysis, patient sex was a significant predictor of arrhythmia recurrence. There was no significant difference in overall mortality between men and women. CONCLUSIONS: Women were more likely than men to have recurrence of atrial fibrillation after successful direct current cardioversion. Patient sex should be taken into account with other clinical factors when making the decision about cardioversion for atrial fibrillation.

Aged↗

Sympathetic neural responses to smoking are age dependent.

OBJECTIVE: Smoking is an important risk factor for cardiovascular disease. Sympathetic responses to cigarette smoking may be implicated in the link between smoking and cardiovascular disease. We tested the hypothesis that the sympathetic neural responses to smoking are age dependent. METHODS: We examined the effects of cigarette smoking and sham smoking on muscle sympathetic nerve activity, blood pressure and heart rate in 14 normotensive middle-aged (49 +/- 4 years) and 12 young (29 +/- 4 years) habitual smokers matched for body mass index (25 +/- 2 kg/m2 in both groups). RESULTS: Sham smoking had no significant effect on sympathetic drive, blood pressure or heart rate in either group. Cigarette smoking increased heart rate in both middle-aged subjects and young subjects. In comparison to younger subjects, middle-aged smokers showed similar smoking-related increases in systolic blood pressure (SBP) [10 +/- 3 versus 12 +/- 2 mmHg, respectively, not significant (NS)]. Smoking decreased sympathetic nerve activity by 28 +/- 12% of baseline values (P < 0.01) in young subjects. However, muscle sympathetic nerve activity did not change significantly after smoking in middle-aged subjects (5 +/- 8%, NS), despite the increased blood pressures, which would be expected to inhibit sympathetic activity. By contrast, in young subjects, the heart rate increase (22 +/- 2 bpm) was greater than that seen in middle-aged subjects (13 +/- 2 bpm, P < 0.01). CONCLUSIONS: The autonomic responses to smoking are age dependent. While blood pressure increases are similar in both groups, young subjects respond to smoking by marked increases in heart rate and suppression of central sympathetic outflow. In middle-aged subjects, the heart rate increase is less marked, but sympathetic vasoconstrictor activity is not suppressed.

Adult↗

Lifestyle, family history and progression of hypertension.

BACKGROUND: Unhealthy lifestyle practices are risk factors for future hypertension. OBJECTIVES: The aim of this study was to investigate the association between lifestyle changes over a 6-year period and the risk of developing sustained hypertension in a cohort of young hypertensive individuals, and to identify the predictors of lifestyle impairment over time. METHODS: Seven-hundred and eighty never-treated hypertensive HARVEST participants, 18-45 years old, were studied. RESULTS: Only modest mean behavioral changes were observed during follow-up. This, however, was the net result of many participants improving and others worsening their lifestyle. Participants with a family history of hypertension (FH+, n = 459) had more undesirable lifestyles (P = 0.004) and higher clinic and ambulatory blood pressures (P = 0.03) at baseline than participants without a family history of hypertension (FH-). During the 6-year follow-up, FH- individuals strikingly worsened their lifestyle while FH+ participants exhibited impressive improvements (P < 0.00001). Other predictors of lifestyle impairment were male gender (P = 0.003) and age (P = 0.02). Adoption of an unfavorable lifestyle was accompanied by an increased risk of developing sustained hypertension (P = 0.04). Initiation of drug therapy for hypertension was significantly higher among FH- than FH+ individuals (53 versus 45%, respectively; P = 0.045). CONCLUSIONS: 'Lower risk' FH- stage 1 hypertensive individuals may initially be at higher risk of developing more severe hypertension in comparison with their FH+ counterparts. This increased risk may be attributed to worsening of their lifestyle profiles over time. Healthy lifestyles should be emphasized to all hypertensive individuals including patients with favorable lifestyle profiles.

Adolescent↗

Pathophysiological characteristics of heart rate recovery in heart failure.

PURPOSE: Heart failure (HF) is associated with blunted HR recovery after exercise. The determinants of altered HR recovery in HF are unknown. The aim of this study was to investigate clinical correlates of HR recovery in HF patients. METHODS: Echocardiography, pulmonary function tests, exercise testing, and neurohormonal measurements were performed in 98 HF patients. HR recovery was calculated as the difference between heart rate at peak exercise and at 1 min into a recovery period. Study subjects were divided into three groups based on HR recovery tertiles: group 1 (HR recovery < or = 6 bpm), group 2 (7 < or = HR recovery < or = 12), and group 3 (HR recovery > or = 13). RESULTS: There were significant differences between the groups in multiple parameters. Compared with group 3, patients in group 1 had greater E/A ratios (1.81 +/- 0.26 vs 0.98 +/- 0.12, P = 0.011), shorter deceleration time (170 +/- 11 vs 223 +/- 11 ms, P = 0.016), and higher plasma atrial natriuretic peptide levels (207 +/- 32 vs 101 +/- 12 pg.mL, P = 0.008), indicating higher left ventricular filling pressures and elevated left atrial pressures. Pulmonary function tests were suggestive of greater restrictive changes in the lungs. Finally, subjects in group 1 had impaired exercise capacity, as evidenced by shorter exercise duration (5.2 +/- 0.2 vs 8.3 +/- 0.4 min, P < 0.001), lower peak VO2 (14.6 +/- 0.6 vs 22.2 +/- 1.0 mL.kg(-1).min(-1), P < 0.001), higher VE/VCO2 ratios (36.4 +/- 1.1 vs 31.1 +/- 0.9, P = 0.001), and reduced chronotropic responses to exercise (39 +/- 3 vs 69 +/- 4 bpm, P < 0.001). CONCLUSION: HR recovery may be a clinically useful index identifying HF patients with distinct echocardiographic, neurohormonal, and hemodynamic characteristics. This may have implications for our understanding of the pathophysiology of impaired HR recovery in HF as well as for the clinical evaluation of such patients.

Analysis of Variance↗

Sympathetic neural outflow and chemoreflex sensitivity are related to spontaneous breathing rate in normal men.

Respiration contributes importantly to short-term modulation of sympathetic nerve activity. However, the relationship between spontaneous breathing rate, chemoreflex function, and direct measures of sympathetic traffic in healthy humans has not been studied previously. We tested the hypothesis that muscle sympathetic nerve activity and chemoreflex sensitivity are linked independently to respiratory rate in normal subjects. We studied 69 normal male subjects aged 29.6+/-8.1 years. Subjects were subdivided according to the tertiles of respiratory rate distributions. Mean respiration rate was 10.6 breaths/min in the first tertile, 14.8 breaths/min in the second tertile, and 18.0 breaths/min in the third tertile. Subjects from the third tertile (faster respiratory rate) had greater sympathetic activity than subjects from the first tertile (slower respiratory rate; 29+/-3 versus 17+/-2 bursts/min; P<0.001). Stepwise multiple linear regression analysis revealed that only respiratory rate was linked independently to sympathetic activity (r=0.42; P<0.001). In comparison to subjects with slow respiratory rate, subjects with fast respiratory rate had greater increases in minute ventilation during both hypercapnia (7.3+/-0.8 versus 3.2+/-1.0 L/min; P=0.005) and hypoxia (5.7+/-0.8 versus 2.4+/-0.7 L/min; P=0.007). Muscle sympathetic nerve activity and chemoreflex sensitivity are linked to spontaneous respiratory rate in normal humans. Faster respiratory rate is associated with higher levels of sympathetic traffic and potentiated responses to hypoxia and hypercapnia. Spontaneous breathing frequency, central sympathetic outflow, and chemoreflex sensitivity exhibit significant and hitherto unrecognized interactions in the modulation of neural circulatory control.

Adult↗

Status of endothelial dependent vasodilation in patients with hyperuricemia.

Hyperuricemia has been associated with an increased risk for cardiovascular disease and increased mortality. However, the biologic mechanisms that link elevated serum uric acid to cardiovascular disease are uncertain. This study tested the hypothesis that elevated serum uric acid is associated with impaired endothelial function in hyperuricemic patients without any overt cardiovascular disease. Seventeen male patients with hyperuricemia (mean age 42+/-4 years) and 9 control subjects (mean age 45+/-5 years) were studied. All subjects were nonsmokers. All patients had never been treated for hyperuricemia, were on no medications, and were free of any other known diseases. Endothelial function was evaluated by flow-mediated dilation measured by ultrasound. Flow-mediated dilation was significantly impaired in patients with hyperuricemia (4.0+/-0.7%) compared with control subjects (6.4+/-0.8%) (p=0.044). Flow-mediated dilation correlated inversely with uric acid levels (r=-0.4, p=0.05). Nitrate-induced dilation was 12.3+/-1.0% in patients with hyperuricemia and 11.8+/-2.3% in control subjects (p=0.82). Impaired endothelial-dependent vasodilation is present in hyperuricemic patients even in the absence of any overt cardiovascular disease. The elevated serum uric acid, per se, may constitute a novel risk factor for endothelial dysfunction.

Adult↗

High sensitivity C-reactive protein: a novel predictor for recurrence of atrial fibrillation after successful cardioversion.

OBJECTIVES: We sought to test the hypothesis that C-reactive protein (CRP) can predict the recurrence of atrial fibrillation (AF) after successful electrical cardioversion (CV). BACKGROUND: In patients with AF, CRP levels are predictive of immediate failure of CV. METHODS: We prospectively measured high-sensitivity CRP in 67 patients with AF or atrial flutter who underwent successful electrical CV. RESULTS: At one-month follow-up, 22 patients (33%) had recurrence of their arrhythmia. Arrhythmia recurrence was associated with significantly higher pre-CV CRP levels (odds ratio [OR] 1.84; 95% confidence interval [CI] 1.14 to 2.98; p = 0.013) even after adjusting for age (OR 2.22; 95% CI 1.25 to 3.93; p = 0.006), for gender (OR 1.89; 95% CI 1.16 to 3.09; p = 0.011), or duration of arrhythmia (OR 1.86; 95% CI 1.13 to 3.07; p = 0.015). On multivariate analysis, CRP was the only independent predictor of arrhythmia recurrence (OR 2.19; 95% CI 1.05 to 4.55; p = 0.036). CONCLUSIONS: Our data suggest that high levels of CRP are associated with an increased risk of recurrence of AF within one month. These data support the hypothesis that anti-inflammatory interventions may help in maintenance of normal sinus rhythm after CV. These data also may have implications for the identification of patients who are most likely to experience substantial benefit from CV therapy for AF.

Aged↗