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PubMed2006

Risk of mortality and adverse cardiovascular outcomes in type 2 diabetes: a comparison of patients treated with sulfonylureas and metformin.

AIMS/HYPOTHESIS: The aim of this study was to evaluate the risk of adverse cardiovascular outcomes in patients with type 2 diabetes newly treated with sulfonylureas and metformin. SUBJECTS AND METHODS: The Diabetes Audit and Research in Tayside Scotland (DARTS) diabetes information system and the Medicines Monitoring Unit (MEMO) dispensed prescribing database for the population of Tayside, Scotland (400,000 people) were employed. Patients newly prescribed with oral hypoglycaemic agents between 1994 and 2001 were classified into five study cohorts according to the treatment received: metformin only, sulfonylureas only, sulfonylureas added to metformin, metformin added to sulfonylureas, and both drugs simultaneously. In Cox regression analyses, we estimated relative risks for all-cause mortality, cardiovascular mortality and cardiovascular hospital admission for patients in the five study cohorts, with metformin monotherapy as the reference group. RESULTS: Of the 5,730 study patients, 1,000 died during a maximum of 8 years follow-up. Patients in the sulfonylureas only cohort had increased risks of mortality and cardiovascular mortality, with unadjusted relative risks of 3.12 (95% CI 2.54-3.84) and 3.71 (95% CI 2.64-5.22), respectively. After adjusting for differences between groups (age, sex, duration of diabetes, blood pressure, cholesterol, HbA(1c), smoking, previous hospital admission, treatment with cardiovascular medication), these relative risks were 1.43 (95% CI 1.15-1.77) and 1.70 (95% CI 1.18-2.45), respectively. Patients in the combination cohorts had significantly increased risks of cardiovascular hospital admission, as well as increased risks of mortality and cardiovascular mortality. CONCLUSIONS/INTERPRETATION: In this cohort study of patients newly treated with oral hypoglycaemic agents, those treated with sulfonylureas only, or combinations of sulfonylureas and metformin, were at higher risk of adverse cardiovascular outcomes than those treated with metformin alone.

Adult↗
PubMed2001

Postprandial blood glucose as a risk factor for cardiovascular disease in Type II diabetes: the epidemiological evidence.

That cardiovascular disease occurs more frequently in patients with Type II (non-insulin-dependent) diabetes mellitus has been recognized for a long time. However, the extent to which hyperglycaemia contributes to atherosclerosis and cardiovascular disease is still not clear. Epidemiological studies published in recent years suggest that postprandial blood glucose might be an independent risk factor of cardiovascular disease. The main results of these studies, which are reviewed in this article, are that subjects from the general population with mild to moderate hyperglycaemia, following oral glucose load, but not in the fasting state, showed an increased cardiovascular risk. Furthermore, the post-challenge as well as postprandial glucose concentrations of subjects with Type II diabetes were found to be directly associated to incident cardiovascular disease independently of fasting glucose. Also, the correction of fasting hyperglycaemia or HbA1 c or both, disregarding the specific correction of postprandial hyperglycaemia was not found to significantly reduce the incidence of cardiovascular disease in patients with Type II diabetes. Finally, the strict control of both preprandial and postprandial hyperglycaemia yielded a substantial reduction of cardiovascular disease in Type II diabetes. Trials specifically designed to address this issue are needed to determine whether postprandial hyperglycaemia plays an independent and causative role in cardiovascular disease in patients with Type II diabetes.

Blood Glucose↗
PubMed2005

The impact of antidiabetic therapies on cardiovascular disease.

Cardiovascular disease disproportionately affects people with diabetes and is a leading cause of death. Glycemic control has so far not been conclusively shown to decrease cardiovascular events. The therapeutic agents used in treating glycemia have different effects on cardiovascular risks and, therefore, may have different effects on outcome. Insulin sensitizers impact cardiovascular risk factors, including dyslipidemia and fibrinolysis. Metformin is the only oral antidiabetic medication shown to decrease cardiovascular events independent of glycemic control. Thiazolidinediones improve insulin resistance and lower insulin concentrations, which is beneficial because hyperinsulinemia is an independent predictor of cardiovascular disease. Insulin therapy acutely reduces cardiovascular mortality and morbidity in patients with diabetes and known coronary artery disease and also in patients with hyperglycemia when critically ill, but the long-term effects are unclear. In contrast, insulin secretagogues have very little effect on both cardiovascular risk factors and outcomes.

Biguanides↗
PubMed2006

Left atrial diameter as an independent predictor of first clinical cardiovascular events in middle-aged and elderly adults: the Strong Heart Study (SHS).

BACKGROUND: Echocardiographic left atrial (LA) volume has been documented to be an independent predictor of cardiovascular events. Less is known about the predictive ability of anteroposterior LA diameter, a simpler measure of LA size obtained routinely during echocardiographic evaluation. METHODS: We investigated the prognostic value of LA diameter for incident cardiovascular events in 2804 American Indians free of clinical cardiovascular disease, valvular disease, and atrial fibrillation. Echocardiographic variables were obtained using standardized methods, and previously derived sex-specific partition values were used to define left ventricular (LV) hypertrophy indexed to height(2.7) (in meters) and LA enlargement (> 4.2 cm in men, > 3.8 cm in women). Cardiovascular events included nonfatal stroke, coronary heart disease, congestive heart failure, and fatal cardiovascular disease based on validated definitions. RESULTS: During a median follow-up of 7 years, 368 events occurred. LA diameter, both as a continuous and as a categorical variable, was significantly associated with incident cardiovascular events in unadjusted analyses. In multivariable analyses that adjusted for age, sex, body mass index, hypertension, diabetes, total cholesterol-high-density lipoprotein cholesterol, smoking, renal insufficiency, LV hypertrophy, abnormal LV systolic and diastolic function, mitral annular calcification, fibrinogen, and C-reactive protein, both LA diameter (risk ratio 1.04/mm, 95% CI 1.02-1.07, P < .002) and LA enlargement (risk ratio 1.57, 95% CI 1.17-2.10, P = .002) remained independent predictors of first cardiovascular events. CONCLUSIONS: In this population-based cohort, LA diameter independently predicted incident cardiovascular events after adjustment for established clinical, echocardiographic, and inflammatory risk factors. This simple measure of LA dilatation can identify individuals at heightened risk who may warrant more aggressive risk factor modification.

Aged↗
PubMed2006

Effect of raloxifene on cardiovascular adverse events in postmenopausal women with osteoporosis.

The impact of selective estrogen receptor modulators on cardiovascular disease outcomes in postmenopausal women remains unclear. This analysis assessed the effect of raloxifene on the incidence of cardiovascular adverse events in postmenopausal women followed for < or =8 years as participants in a 4-year osteoporosis treatment trial and a subsequent 4-year follow-up trial. The Continuing Outcomes Relevant to Evista (CORE) trial, designed to determine the effect of raloxifene on the incidence of invasive breast cancer, was a 4-year follow-up study to the 4-year Multiple Outcomes of Raloxifene Evaluation (MORE) osteoporosis treatment trial. Of the 7,705 participants originally enrolled in MORE, 4,011 were enrolled in CORE and thus participated in both trials (MORE-CORE participants). The incidence of serious cardiovascular (i.e., coronary and cerebrovascular) adverse events during 8 years, confirmed by external adjudication in the 2 trials, was compared between treatment groups using Cox proportional hazards models. The 8-year incidence of serious cardiovascular adverse events did not differ significantly between the raloxifene (5.5%) and placebo (4.7%) groups (hazard ratio [HR] 1.16, 95% confidence interval [CI] 0.86 to 1.56). Similar results were obtained when coronary (HR 1.22, 95% CI 0.82 to 1.83) or cerebrovascular (HR 1.19, 95% CI 0.78 to 1.84) events were analyzed separately, and when cardiovascular events were analyzed in the 459 MORE-CORE participants who were at increased risk of cardiovascular events by previously established criteria (HR 1.03, 95% CI 0.58 to 1.82). In conclusion, we found no evidence of a beneficial or harmful effect of raloxifene on the incidence of cardiovascular events overall, or coronary or cerebrovascular events, in postmenopausal osteoporotic women at relatively low risk of cardiovascular events.

Aged↗
PubMed2006

Bupropion for smokers hospitalized with acute cardiovascular disease.

PURPOSE: Smoking cessation after myocardial infarction reduces cardiovascular mortality, but many smokers cannot quit despite state-of-the-art counseling intervention. Bupropion is effective for smoking cessation, but its safety and efficacy in hospitalized smokers with acute cardiovascular disease is unknown. METHODS: A five-hospital randomized double-blind placebo-controlled trial assessed the safety and efficacy of 12 weeks of sustained-release bupropion (300 mg) or placebo in 248 smokers admitted for acute cardiovascular disease, primarily myocardial infarction and unstable angina. All subjects had smoking counseling in the hospital and for 12 weeks after discharge. Cotinine-validated 7-day tobacco abstinence, cardiovascular mortality, and new cardiovascular events were assessed at 3 months (end-of-treatment) and 1 year. RESULTS: Validated tobacco abstinence rates in bupropion and placebo groups were 37.1% vs 26.8% (OR 1.61, 95% CI, 0.94-2.76; P=.08) at 3 months and 25.0% vs 21.3% (OR, 1.23, 95% CI, 0.68-2.23, P=.49) at 1 year. The adjusted odds ratio, after controlling for cigarettes per day, depression symptoms, prior bupropion use, hypertension, and length of stay, was 1.91 (95% CI, 1.06-3.40, P=.03) at 3 months and 1.51 (95% CI, 0.81-2.83) at 1 year. Bupropion and placebo groups did not differ in cardiovascular mortality at 1 year (0% vs 2%), in blood pressure at follow-up, or in cardiovascular events at end-of-treatment (16% vs 14%, incidence rate ratio [IRR]1.22 (95% CI: 0.64-2.33) or 1 year (26% vs 18%, IRR 1.56, 95% CI 0.91-2.69). CONCLUSIONS: Bupropion improved short-term but not long-term smoking cessation rates over intensive counseling and appeared to be safe in hospitalized smokers with acute cardiovascular disease.

Acute Disease↗
PubMed2005

apoB/apoA-I ratio is related to femoral artery plaques and is predictive for future cardiovascular events in healthy men.

OBJECTIVES: The aim of the present study was to investigate the association between serum concentrations of apoB, apoA-I and the apoB/apoA-I ratio and future cardiovascular events in a group of healthy 58-year-old men during 6.6 years of follow-up. A further aim was to investigate the concentrations of apoB, apoA-I and the apoB/apoA-I ratio to the association of plaque occurrence in the carotid and femoral arteries. BACKGROUND: Previous studies have shown that the apoB/apoA-I ratio is an important cardiovascular risk factor, whereas the association between apoB/apoA-I ratio and presence of atherosclerotic plaques in the carotid and femoral arteries has been less investigated. METHODS: The carotid and femoral arteries were examined by high-resolution B-mode ultrasound in 391, 58-year-old men identified by screening in the city of Göteborg, Sweden. Assessment of plaque occurrence and measurement of apolipoproteins (apoA-I and apoB) was performed. RESULTS: Subjects with an apoB/apoA-I ratio >/=0.9 had a significantly increased risk to suffer a cardiovascular event during 6.6 years of follow-up (OR 3.07, 95% CI 1.22-7.71), while no difference in risk for cardiovascular events was observed for subjects with LDL cholesterol >3.4 mmol/L compared to subjects <3.4 mmol/L (OR 1.04, 95% CI 0.37-2.46). A greater risk for plaques in the femoral artery was also observed in subjects with an apoB/apoA-I ratio >/=0.9 compared to subjects <0.9 (OR 3.06, 95% CI 1.22-7.70). In a multiple logistic regression model, both elevated apoB/apoA-I ratio and plaque occurrence in the femoral artery were of significant importance for cardiovascular events during follow-up. CONCLUSIONS: The results showed that the apoB/apoA-I ratio was associated with arteriosclerosis in the femoral artery, and predicted future cardiovascular events. These observations, and the fact that apoB and apoA-I can be measured in the non-fasting state with high precision, in combination with the finding that LDL cholesterol did not predict cardiovascular disease, support results from other studies that the apoB/apoA-I ratio may be a superior risk marker for cardiovascular disease.

Apolipoprotein A-I↗
PubMed2003

Relative effects of harassment, frustration, and task characteristics on cardiovascular reactivity.

Effects of anger induction procedures such as frustration and harassment on cardiovascular reactivity have been demonstrated in a wide range of experimental situations. Similarly, heightened cardiovascular reactivity has been associated with a diverse range of tasks involving active coping, competition and interpersonal interaction. The present study sought to directly compare the relative effects of these two important ways of inducing cardiovascular changes. One hundred and five university students performed two tasks that differed in the degree of active coping and interpersonal competition: a competitive psychomotor task and a problem-solving task. States of anger were induced during both tasks by means of harassment, frustration or frustration+harassment. Task-related changes in heart rate, systolic blood pressure, diastolic blood pressure, pulse volume amplitude and respiratory sinus arrhythmia amplitude were monitored. The competitive psychomotor task produced greater cardiovascular reactivity than did the problem-solving task. Harassment and frustration+harassment provoked more cardiovascular reactivity than did frustration alone. However, harassment and frustration+harassment had the greatest cardiovascular effects in the competitive task, whereas frustration had the greatest cardiovascular effects in the problem-solving task. In this sense, the increases on cardiovascular reactivity seem to depend on the interaction between anger induction procedures and the context in which anger is provoked.

Adaptation, Psychological↗
PubMed2001

Periodontal disease and risk of subsequent cardiovascular disease in U.S. male physicians.

OBJECTIVES: We sought to prospectively assess whether self-reported periodontal disease is associated with subsequent risk of cardiovascular disease in a large population of male physicians. BACKGROUND: Periodontal disease, the result of a complex interplay of bacterial infection and chronic inflammation, has been suggested to be a predictor of cardiovascular disease. METHODS: Physicians' Health Study I was a randomized, double-blind, placebo-controlled trial of aspirin and beta-carotene in 22,071 U.S. male physicians. A total of 22,037 physicians provided self-reports of presence or absence of periodontal disease at study entry and were included in this analysis. RESULTS: A total of 2,653 physicians reported a personal history of periodontal disease at baseline. During an average of 12.3 years of follow-up, there were 797 nonfatal myocardial infarctions, 631 nonfatal strokes and 614 cardiovascular deaths. Thus, for each end point, the study had >90% power to detect a clinically important increased risk of 50%. In Cox proportional hazards regression analysis adjusted for age and treatment assignment, physicians who reported periodontal disease at baseline had slightly elevated, but statistically nonsignificant, relative risks (RR) of nonfatal myocardial infarction, (RR, 1.12; 95% confidence interval [CI], 0.92 to 1.36), nonfatal stroke (RR, 1.10; CI, 0.88 to 1.37) and cardiovascular death (RR, 1.20; CI, 0.97 to 1.49). Relative risk for a combined end point of all important cardiovascular events (first occurrence of nonfatal myocardial infarction, nonfatal stroke or cardiovascular death) was 1.13 (CI, 0.99 to 1.28). After adjustment for other cardiovascular risk factors, RRs were all attenuated and nonsignificant. CONCLUSIONS: These prospective data suggest that self-reported periodontal disease is not an independent predictor of subsequent cardiovascular disease in middle-aged to elderly men.

Adult↗
PubMed2003

The impact of cardiovascular comorbidity on the outcome of surgery for stage I and II non-small-cell lung cancer.

OBJECTIVE: The association between lung malignancy and cardiovascular disease has been frequently reported though its therapeutic and prognostic implications not thoroughly analyzed. This study aims at assessing the possible impact of coexisting cardiovascular disease on the outcome of surgical treatment of non small cell lung cancer (NSCLC). METHODS: Among 247 consecutive patients undergone surgery for stage I and II NSCLC between 1990 and 1997, 34 (13.7%) had a cardiovascular comorbidity going to be treated by surgery, namely coronary artery disease (n=14), carotid stenosis (n=21), abdominal aortic aneurysm (n=9) and lower limbs arteriopathy (n=7). Among 22 patients (64.7%) who underwent cardiac/vascular surgery first, operation was performed after a median interval of 4.5 weeks. In five of this subset lung cancer was incidentally detected. In the other patients the cardiovascular disease was diagnosed and treated after the lung cancer had been detected and operated with a median interval of 3.5 months from thoracic procedure. Surgical procedures for lung cancer were three pneumonectomies, 12 lobectomies, 19 wedge resections. Uni and multivariate analysis for risk factors was carried out. RESULTS: In the group with cardiovascular comorbidity overall postoperative mortality was 9%, while morbidity rate was 58.8%, both of them primarily caused by cardiovascular disease and significantly higher for major resections. The 3- and 5-year survival rates were 54.8% and 35.5% compared to 69.2% and 56.4% among patients without cardiovascular comorbidity (P=0.01) while the timing of vascular surgery (before or after thoracic procedure) did not significantly affect survival. Multifocal vascular disease resulted the only positive factor at multivariate analysis (P=0.005, Odd Ratio=3.51, 95% Confidence Interval=1.4-8.4). CONCLUSIONS: Cardiovascular disease seems to have significant impact on survival and morbidity in patients undergone surgery for lung cancer, especially in presence of multifocal vascular disease and following major resections. The timing of vascular surgery and the extension of resection should rely on the severity of vascular disease, anaesthesiologist's and surgeon's final evaluation.

Aged↗
PubMed2006

Troponin T, left ventricular mass, and function are excellent predictors of cardiovascular congestion in peritoneal dialysis.

Patients on maintenance peritoneal dialysis (PD) are frequently complicated with volume overload. In this study, we sought to evaluate troponin T testing alone or in combination with echocardiographic measures in predicting cardiovascular congestion in PD patients. This was a prospective study of 222 chronic PD patients with echocardiography and measurement of serum troponin T carried out at baseline. Patients were followed for 3 years or until death. The end point was first episode of cardiovascular congestion. Troponin T emerged as an independent predictor of cardiovascular congestion (hazard ratio, 2.98, 95% confidence intervals (CI), 1.19-7.42) in a multivariable Cox regression model, including also left ventricular mass index (LVMi) and ejection fraction (EF). Patients with troponin T>median (0.06 microg/l) and EF median but EF>50% had a 3.10-fold (95% CI, 1.71-5.63) and 1.88-fold (95% CI, 1.05-3.38) adjusted risk of cardiovascular congestion, respectively, than those with troponin T 50%. Patients with troponin T>median and LVMi>or=median (96.23 g/m2.7) had a 2.68-fold (95% CI, 1.39-5.19) adjusted risk of cardiovascular congestion than those with troponin T<or=median and LVMi <median. In conclusion, troponin T predicts cardiovascular congestion in chronic PD patients without acute myocardial ischemia and provides incremental prognostic value for cardiovascular congestion when used in combination with LVM and EF. This easily available parameter adds significant value to echocardiography in identifying PD patients at risk of cardiovascular congestion.

Adult↗
PubMed2001

Cardiovascular effects of tamoxifen in women with and without heart disease: breast cancer prevention trial. National Surgical Adjuvant Breast and Bowel Project Breast Cancer Prevention Trial Investigators.

BACKGROUND: The overall effect of prophylactic tamoxifen in women depends on the balance between the effects of the drug, which include preventing breast cancer and altering cardiovascular risk. In a recent clinical trial, postmenopausal estrogen-progestin therapy was shown to increase the risk of early cardiovascular events among women with a history of coronary heart disease (CHD). The cardiovascular effects of tamoxifen in women with and without CHD are not known. The National Surgical Adjuvant Breast and Bowel Project Breast Cancer Prevention Trial (BCPT) is the only clinical trial that provides data to assess the cardiovascular effects of tamoxifen in women with and without CHD. METHODS: A total of 13 388 women at increased risk for breast cancer were randomly assigned in the BCPT to receive either tamoxifen (20 mg/day) or placebo. Cardiovascular follow-up was available for 13 194 women, 1048 of whom had prior clinical CHD. Fatal and nonfatal myocardial infarction, unstable angina, and severe angina were tabulated (mean follow-up: 49 months). All statistical tests were two-sided. RESULTS: Cardiovascular event rates were not statistically significantly different between women assigned to receive tamoxifen and those assigned to receive placebo, independent of pre-existing CHD. Among women without CHD (6074 on tamoxifen versus 6072 on placebo), risk ratios (95% confidence intervals [CIs]) for tamoxifen users were 1.75 (0.44 to 8.13) for fatal myocardial infarction, 1.11 (0.55 to 2.28) for nonfatal myocardial infarction, 0.69 (0.29 to 1.57) for unstable angina, and 0.83 (0.32 to 2.10) for severe angina. In women with CHD (516 on tamoxifen versus 532 on placebo), risk ratios (95% CIs) for tamoxifen users were 0.00 (0 to 1.58) for fatal myocardial infarction, 1.25 (0.32 to 5.18) for nonfatal myocardial infarction, 2.26 (0.87 to 6.55) for unstable angina, and 1.39 (0.23 to 9.47) for severe angina. There was no evidence that the lack of association between tamoxifen and cardiovascular events was related to an early increase in risk that may have been offset by a late decrease in risk. CONCLUSION: When used for breast cancer prevention in women with or without heart disease, tamoxifen is not associated with beneficial or adverse cardiovascular effects.

Angina Pectoris↗
PubMed2000

Research Agenda for Cardiovascular Aging: Humans to Molecules.

Clinical manifestations of specific cardiovascular diseases, e.g., atherosclerosis and hypertension, that lead to heart failure and stroke likely become altered in older persons of advanced age because interactions occur between age-associated cardiovascular changes in health and specific pathophysiologic mechanisms that underlie cardiovascular diseases. The interactions result in a lower threshold for clinical symptoms, and greater severity and poorer prognosis of these diseases in older vs. younger persons. In this regard, cardiovascular changes that occur during aging in health ought not to be considered to reflect a "normal process"; rather these specific age-associated changes must be construed as specific "risk factors" for the aforementioned cardiovascular diseases and ought to become targets of interventions designed to prevent the epidemic of cardiovascular disease in later life. Such a strategy would thus advocate preventive treatment for what is now considered to be "normal cardiovascular aging." Effective and efficient prevention of the "risks" associated with cardiovascular aging in apparent health requires a fundamental understanding of these changes ranging in scope from humans to molecules. An opinion regarding specific directions for research aimed toward the achievement of this understanding is provided. (c) 2000 by CVRR, Inc.

Journal Article↗
PubMed2005

Insulin treatment and cardiovascular disease; friend or foe? A point of view.

BACKGROUND: Several observational studies have shown that higher insulin levels are associated with an increased risk of cardiovascular disease. If higher endogenous insulin levels are causally related to cardiovascular disease, one might expect an increased risk of cardiovascular disease in patients treated with insulin, as this results in high circulating insulin levels. Such risk elevation might counteract the benefits of tight glucose control. Our objective was to explore the relationship between insulin therapy and cardiovascular disease in Type 1 and Type 2 diabetes mellitus using information from available literature. SUMMARY OF COMMENT: Several experimental studies in animals and humans support the presence of a harmful effect of insulin on the vascular endothelium. In prospective follow-up studies increased insulin dosage was associated with increased risks of cardiovascular disease, although confounding by indication could not be excluded. Randomized controlled trials in diabetic patients, comparing conventional with intensive glucose-lowering treatment, although showing a reduction in microvascular disease, showed no significant difference in the incidence of cardiovascular disease. The results with respect to exposure to insulin are, however, difficult to interpret due to insufficient information on exposure to insulin levels as well as confounding by glycaemic control and body mass index. In addition, these studies were not designed to address the question whether higher insulin use relates to increased cardiovascular risk. CONCLUSION: Published research provides conflicting evidence as to whether exposure to high levels of exogenous insulin in diabetes mellitus affects the risk of cardiovascular disease. The currently available studies have a number of serious methodological restraints that limit accurate interpretation and conclusions in this area.

Diabetes Mellitus, Type 1↗
PubMed2004

Medullary substrate and differential cardiovascular responses during stimulation of specific acupoints.

Electroacupuncture (EA) at P5-P6 acupoints overlying the median nerve reduces premotor sympathetic cardiovascular neuronal activity in the rostral ventral lateral medulla (rVLM) and visceral reflex pressor responses. In previous studies, we have noted different durations of influence of EA comparing P5-P6 and S36-S37 acupoints, suggesting that point specificity may exist. The purpose of this study was to evaluate the influence of stimulating P5-P6 (overlying the median nerve), LI4-L7 (overlying branches of the median nerve and the superficial radial nerve), LI6-LI7 (overlying the superficial radial nerve), LI10-LI11 (overlying the deep radial nerves), S36-S37 (overlying the deep peroneal nerves), or K1-B67 (overlying terminal branches of the tibial nerves) specific acupoints, overlying deep and superficial somatic nerves, on the excitatory cardiovascular reflex and rVLM responses evoked by stimulation of chemosensitive receptors in the cat's gallbladder with bradykinin (BK) or direct splanchnic nerve (SN) stimulation. We observed point-specific differences in magnitude and duration of EA inhibition between P5-P6 or LI10-LI11 and LI4-L7 or S36-S37 in responses to 30-min stimulation with low-frequency, low-current EA. EA at LI6-LI7 and K1-B67 acupoints as well as direct stimulation of the superficial radial nerve did not cause any cardiovascular or rVLM neuronal effects. Cardiovascular neurons in the rVLM, a subset of which were classified as premotor sympathetic cells, responded to brief (30 s) stimulation of the SN as well as acupoints P5-P6, LI10-LI11, LI4-L7, S36-S37, LI6-LI7, or K1-B67, or underlying somatic pathways in a fashion similar to the reflex responses. In fact, we observed a significant linear relationship (r(2) = 0.71) between the evoked rVLM response and reflex change in mean arterial blood pressure. In addition, EA stimulation at P5-P6 and LI4-L7 decreased rVLM neuronal activity by 41 and 12%, respectively, for >1 h, demonstrating that prolonged input into the medulla during stimulation of somatic nerves, depending on the degree of convergence, leads to more or less inhibition of activity of these cardiovascular neurons. Thus EA at acupoints overlying deep and superficial somatic nerves leads to point-specific effects on cardiovascular reflex responses. In a similar manner, sympathetic cardiovascular rVLM neurons that respond to both visceral (reflex) and somatic (EA) nerve stimulation manifest graded responses during stimulation of specific acupoints, suggesting that this medullary region plays a role in site-specific inhibition of cardiovascular reflex responses by acupuncture.

Acupuncture Points↗
PubMed1998

Altered cardiovascular variability in obstructive sleep apnea.

BACKGROUND: Altered cardiovascular variability is a prognostic indicator for cardiovascular events. Patients with obstructive sleep apnea (OSA) are at an increased risk for cardiovascular disease. We tested the hypothesis that OSA is accompanied by alterations in cardiovascular variability, even in the absence of overt cardiovascular disease. METHODS AND RESULTS: Spectral analysis of variability of muscle sympathetic nerve activity, RR interval, and blood pressure were obtained during undisturbed supine rest in 15 patients with moderate-to-severe OSA, 18 patients with mild OSA, and 16 healthy control subjects in whom sleep disordered breathing was excluded by complete overnight polysomnography. Patients with OSA were newly diagnosed, never treated for OSA, and free of any other known diseases. Patients with moderate-to-severe OSA had shorter RR intervals (793+/-27 ms) and increased sympathetic burst frequency (49+/-4 bursts/min) compared with control subjects (947+/-42 ms; 24+/-3 bursts/min; P=0.008 and P<0.001, respectively). In these patients, total variance of RR was reduced (P=0.01) and spectral analysis of RR variability showed an increase in low frequency normalized units, a decrease in high frequency normalized units, and an increase in the ratio of low to high frequency (all P<0.05). Even though blood pressure was similar to that of the control subjects, blood pressure variance in patients with moderate-to-severe OSA was more than double the variance in control subjects (P=0.01). Patients with mild OSA also had a reduction in RR variance (P=0.02) in the absence of any significant difference in absolute RR interval. For all patients with OSA, linear regression showed a positive correlation (r=0.40; P=0.02) between sleep apnea severity and blood pressure variance. CONCLUSIONS: Cardiovascular variability is altered in patients with OSA. This alteration is evident even in the absence of hypertension, heart failure, or other disease states and may be linked to the severity of OSA. Abnormalities in cardiovascular variability may be implicated in the subsequent development of overt cardiovascular disease in patients with OSA.

Adult↗
PubMed1998

Pulse pressure and cardiovascular mortality in normotensive and hypertensive subjects.

There is now increasing evidence that high pulse pressure, which is an indicator of large artery stiffness, is an independent risk factor for cardiovascular mortality, especially coronary mortality, in different populations. We have recently shown in a large French population that in male subjects aged 40 to 69 years, increased pulse pressure was a strong predictor of cardiovascular mortality, especially coronary mortality. In the present report, we analyzed the effect of pulse pressure in men and women of the same cohort after classifying them as normotensive (systolic blood pressure [SBP] <140 mm Hg and DBP <90 mm Hg) or hypertensive (SBP >/=160 mm Hg or DBP >/=95 mm Hg). After adjustment for age, mean blood pressure, and other risk factors, the relative risk (95% confidence limits) for cardiovascular mortality for an increase of 10 mm Hg of pulse pressure was 1.20 (1.01 to 1.44) in normotensives and 1.09 (1.03 to 1.14) in hypertensives. Cardiovascular and coronary death rates were similar in the group of normotensive men with a pulse pressure >50 mm Hg and in the group of hypertensive men with a pulse pressure <45 mm Hg. No association between cardiovascular mortality and pulse pressure was observed in either normotensive or hypertensive women (0.85 [0.60 to 1.21] and 1.0 [0. 91 to 1.11], respectively). Low mortality rates could explain this observation in normotensive but not in hypertensive women, in whom cardiovascular mortality rates were relatively high. Because a high pulse pressure in men is an independent predictor of cardiovascular mortality in both hypertensives and in those considered as having normal blood pressure, this parameter could aid in evaluating cardiovascular risk.

Adult↗
PubMed2002

Lipid-lowering drug use and cardiovascular events after myocardial infarction.

BACKGROUND: The benefits of lipid-lowering drug treatment for the secondary prevention of coronary heart disease have been well established by randomized, controlled trials. Nonetheless, the risk of events has not been compared directly for inhibitors of hydroxymethylglutaryl coenzyme A reductase (statins) and non-statin lipid-lowering drugs. Further, it remains uncertain whether patients in usual practice who are treated with lipid-lowering drugs after myocardial infarction (MI) gain a similar benefit with regard to the risk of cardiovascular events compared with patients in randomized, controlled trials. OBJECTIVE: To assess the association between lipid-lowering drug therapies in usual clinical practice and the risk of cardiovascular events in patients with a first MI who were discharged alive from the hospital. METHODS: An inception-cohort study was performed among 1956 enrollees of Group Health Cooperative who sustained an incident MI between July 1986 and December 1996 and survived for at least 6 months after hospitalization. Subjects with untreated low-density-lipoprotein cholesterol concentrations > 130 mg/dL or untreated total cholesterol concentrations >200 mg/dL were included. The median duration of follow-up after the first MI was 3.3 years. Medical record review was used to collect information on cardiovascular risk factors. Computerized pharmacy records were used to assess antihyperlipidemic drug use during the first 6 months after hospitalization. RESULTS: Compared with 1263 subjects who did not receive lipid-lowering drug treatment, 373 subjects who received statins had a lower risk of recurrent coronary events (relative risk [RR] 0.59; 95% CI 0.39 to 0.89), stroke (RR 0.82; 95% CI 0.35 to 1.95), atherosclerotic cardiovascular mortality (RR 0.49; 95% CI 0.21 to 1.13), and any atherosclerotic cardiovascular event (RR 0.63; 95% CI 0.40 to 0.98). Among 320 subjects who used non-statin drug therapies, the RRs were 0.66 (95% CI 0.45 to 0.97) for recurrent coronary events, 0.95 (95% CI 0.46 to 1.95) for stroke, 0.68 (95% CI 0.35 to 1.32) for cardiovascular mortality, and 0.77 (95% CI 0.53 to 1.11) for any atherosclerotic cardiovascular event, compared with untreated hyperlipidemic patients. CONCLUSIONS: In this study of MI survivors, the use of lipid-lowering drug therapies after hospitalization was associated with a reduced risk of cardiovascular events. These results emphasize the importance of lipid-lowering drug treatment in patients with hyperlipidemia who survive a first MI.

Cholesterol↗