Global Pulse: The latest cardiovascular highlights

Cardiology Review® OnlineFebruary 2009
Volume 26
Issue 2

Sleep deprivation associated with more coronary artery calcification: Another reason to sleep well

Longer sleep duration was associated with reduced incidence of coronary artery calcification in a 5-year ancillary study of CARDIA (Coronary Artery Risk Development in Young Adults) published in December 2008 in JAMA. This finding remained robust after accounting for potential mediators (lipid levels, blood pressure, body mass index, diabetes, inflammatory markers, alcohol consumption, depression, hostility, and self-reported medical conditions) and confounders (age, sex, race, education, apnea risk, and smoking status). As the first study to explore the relationship between sleep duration and calcification, the study raises more questions than it answers.

The association between sleep duration and calcification was found to be “robust and novel,” wrote Christopher Ryan King, BS, University of Chicago, Chicago, IL, and colleagues. The authors note that future studies are needed to extend these results and confirm them in other cohorts.

CARDIA, initiated in 1985, is a large, ongoing, prospective, multicenter study of the evolution of cardiovascular risk factors in people aged 18 to 30 years. The sleep study was based on a healthy, middle-aged (35-47 years old at year 15 of CARDIA), observational cohort of 670 CARDIA participants. All subjects underwent objective and subjective sleep evaluation. Objective sleep evaluation was based on actigraphy data collected by a wrist activity monitor, and subjective evaluations included a self-reported description of sleep plus answers to 3 validated sleep questionnaires. A baseline computed tomography (CT) scan to determine the presence of coronary calcification was performed on 613 subjects. The final analysis was based on 535 subjects who had both a baseline and follow-up CT scan at 5 years.

At 5 years, 61 subjects (12.3%) had evidence of coronary artery calcification. Longer duration of sleep was associated with a significantly reduced incidence of calcification (P = .01). One extra hour of sleep decreased the estimated odds of calcification by 33%, and this relationship persisted across the range of measured sleep. A subject’s sex, race, and other potential mediators did not attenuate the observed relationship between sleep duration and calcification. The magnitude of the observed effect is similar to the effect of established coronary artery risk factors, wrote the authors. For example, the risk reduction achieved with 1 additional hour of sleep is similar to that achieved with a reduction of 16.5 mm Hg in systolic blood pressure.

The authors cited several limitations of the study, including its size, the reliability of methods used to obtain sleep measures, and the timing of measurements of calcification. The study’s main limitation is the lack of a clinical apnea diagnosis. The Berlin Questionnaire was used to identify high-risk individuals, the authors explained, which should include almost all persons with apnea as well as some without it. Calcification as an end point, however, may not be an accurate predictor of clinical outcomes because people with calcification may not necessarily have clinical events.


King CR, Knutson KL, Rathouz PJ, et al. Short sleep duration and incident coronary artery calcification. JAMA. 2008;300(24):2859-2866.

No significant cardiovascular benefit from intensive glucose control in patients with poorly controlled type 2 diabetes

Intensive glucose control failed to improve the rates of cardiovascular events, death, or microvascular complications compared with standard glucose control in patients with poorly controlled advanced type 2 diabetes, according to the Veterans Affairs Diabetes Trial (VADT), a randomized, prospective, open-label trial of military veterans reported in the January 8, 2009, issue of the New England Journal of Medicine.

Studies to date have had mixed results in determining whether glucose control independently reduces cardiovascular complications. The present study, together with results of ACCORD (Action to Control Cardiovascular Risk in Diabetes) and ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation), failed to show a decrease in cardiovascular events with intensive glucose control, and in all 3 trials, the rates of hypoglycemia and weight gain were higher in the intensive-therapy group. Intensive glucose control had no benefit over 5 to 6 years of followup. For the time being, appropriate management of patients with poorly controlled type 2 diabetes should focus on hypertension, dyslipidemia, and other cardiovascular risk factors to prevent cardiovascular morbidity and mortality, wrote lead author William Duckworth, MD, Phoenix Veterans Affairs Health Care Center, Phoenix, AZ, and colleagues.

VADT included 1791 military veterans with a mean age of 60.4 years. Mean time since diagnosis of diabetes was 11.5 years. Mean body mass index was 31.3, and mean glycated hemoglobin was 9.4%. At baseline, hypertension was present in 72% of patients and 40% already had a cardiovascular event. Microvascular complications had been previously reported in 62%, and 52% were receiving insulin. Patients were randomized to intensive glucose control or standard glucose control, with the goal of an absolute reduction of 1.5% in the glycated hemoglobin level in the intensive-therapy group compared with the standard-therapy group. Other modifiable risk factors were treated identically in both groups.

At a median follow-up of 5.6 years, median glycated hemoglobin levels were 8.4% for those treated with standard therapy and 6.9% in the intensive-therapy group, meeting the predetermined goal for this measure. The primary end point was time from randomization to the first occurrence of a major cardiovascular event (composite of myocardial infarction, stroke, death from cardiovascular causes, congestive heart failure, surgery for vascular disease, inoperable coronary disease, and amputation for ischemic gangrene). No significant difference was seen between the 2 groups for the primary outcome, which occurred in 264 patients in the standard-therapy group and 235 in the intensive-therapy group. Looking at individual components of the primary outcome and the rate of death from any cause, no significant difference was seen between the 2 groups. Also, no significant difference was seen for microvascular complications. The rate of adverse events, mainly hypoglycemia, was actually higher in the intensive-therapy group: 17.6% for standard therapy and 24.1% for intensive therapy.

Study limitations included a population restricted to veterans, making it difficult to extrapolate the findings to women. The study protocol did not include newer agents that are now being used to treat type 2 diabetes, and it is possible that these agents would have different effects. Additionally, it is possible that with longer follow-up, a delayed benefit of intensive control may emerge. “Intensive glycemic control earlier in the disease course may produce benefit, especially if severe hypoglycemia is avoided,” wrote the authors.


Duckworth W, Abraira C, Moritz T, et al; VADT Investigators. Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med. 2009;360(2):129-139.

Which patients should be the highest priority for intensive preventive management in primary care?

Patients with prior cardiovascular disease (CVD) had a 20% higher absolute risk of having another CVD event at 5 years compared with those who had no prior CVD, based on a large study of primary care patients conducted by A.J. Kerr, MD, University of Auckland, New Zealand, and colleagues, and published in Heart. Based on this finding, the authors indicate that patients with prior CVD “should be the highest priority for preventive management in primary care.” The authors state that dichotomizing primary and secondary prevention separates patients with and without prior CVD, and that these patients would be better served by conceptualizing CVD as a spectrum of disease with a unified approach.

CVD risk assessments were generated between 2002 and 2007 using a Web-based Framingham risk prediction algorithm (ie, PREDICT-CVD) in routine primary care. Individualized risk profiles were then linked to national hospitalization and death records. Observed and predicted risk, according to the Framingham algorithm, were compared in patients with and without prior CVD.

Of 35,760 patients between 30 and 74 years of age, 3728 (10.4%) had prior CVD. As would be expected, these patients were older, slightly more likely to be men, and more likely to smoke and to have diabetes. Of these patients, 71.8% had a history of ischemic heart disease, 24.2% had ischemic strokes, and 13.7% reported peripheral vascular disease.

Follow-up was a mean of 2.05 years per person (range, 0.04-4.97 years). Forty-two percent of the 1216 first CVD events occurred in patients with prior CVD, and 58% occurred in those with no prior CVD. More than half of the first events in each group were related to ischemic heart disease. The mean 5-year CVD risk was 28.6% in those with prior CVD compared with 5.2% in those without prior CVD. When stratified according to Framingham CVD risk equation, the 5-year risk among those with prior CVD ranged from about 20% in the lowest risk group to about 50% in the highest risk group.

In those without prior CVD, the predicted Framingham 5-year CVD risk correlated well with the observed risk extrapolated to 5 years. In the highest risk Framingham group (>20% 5-year risk), the observed risk was 25.3%.

“Given that patients at highest absolute risk stand to gain the most from CVD risk management, these findings provide strong support for aggressive management of patients with prior CVD as a high priority in primary care,” the authors note.


Kerr AJ, Broad J, Wells S, Riddell T, Jackson R. Should the first priority in cardiovascular risk management be those with prior cardiovascular disease? Heart. 2009;95(2):125-129.

Sodium to potassium excretion ratio may identify those at increased risk for subsequent CVD

A higher sodium to potassium excretion ratio was associated with increased risk for cardiovascular disease (CVD) and was a more accurate predictor of subsequent CVD events than either sodium or potassium excretion rate alone. This finding emerged in 10- and 15-year follow-up data from the TOHP (Trials of Hypertension Prevention) trials reported in Archives of Internal Medicine.

“We found that the sodium to potassium excretion ratio was the strongest of the 3 measures in predicting CVD and that the effect of urinary or sodium excretion was enhanced when the other was included in the model, supporting the notion that the joint activities of these 2 electrolytes may have an important biologic role [in CVD],” wrote Nancy R. Cook, ScD, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, and colleagues.

Evidence suggests that efforts at sodium reduction or potassium substitution may reduce risk of CVD. Several studies suggest that a high sodium to potassium excretion ratio is associated with increased blood pressure and subsequent CVD. Studies to date have used imperfect measures of these electrolytes. The present study sought to determine the relationship of sodium and potassium urinary excretion rates and the sodium to potassium ratio with risk of subsequent CVD.

Two TOHP trials (TOHP I and TOHP II) of nonpharmacologic interventions aimed at reducing blood pressure were conducted in individuals with prehypertension (high-normal blood pressure). Both studies collected 24-hour urinary excretions from adult participants who were between the ages of 30 and 54 years at study initiation. The relationship of a mean of 3 to 7 urinary excretions of sodium and potassium over 24 hours and their ratio with subsequent CVD events was assessed only in individuals not assigned to an active sodium reduction intervention. CVD events included stroke, myocardial infraction, coronary revascularization, or CVD mortality.

Follow-up information was obtained on 2275 participants with 193 events. A positive relationship was found between urinary sodium excretion and CVD, and a suggested inverse relationship was found for urinary potassium excretion and CVD, but neither measure was statistically significant when considered separately.

“Both measures strengthened when modeled jointly, with opposite but similar effects on risk. However, the sodium to potassium excretion ratio displayed the strongest and statistically significant association, with a 24% increase in risk per unit of the ratio that was similar for coronary heart disease and stroke and was consistent across subgroups,” the authors wrote.

The data support reduced CVD risk among subjects with lower sodium intake, higher potassium intake, or both, which is in line with 2005 US dietary guidelines.

The study was funded by the National Heart, Lung, and Blood Institute, National Institutes of Health. The authors had no financial disclosures to report.


Cook NR, Obarzanek E, Cutler JA, et al. Joint effects of sodium and potassium intake on subsequent cardiovascular disease: the trials of hypertension prevention follow-up study. Arch Intern Med. 2009;169(1):32-40.

Cardiocerebral resuscitation improves survival in cardiac arrest

Cardiocerebral resuscitation (CCR) is a relatively new approach for resuscitation of patients with cardiac arrest. This approach was developed by the University of Arizona Sarver Heart Center Resuscitation Group. CCR advocates continuous chest compressions without mouth-to-mouth ventilations for witnessed cardiac arrest. It is hoped that eliminating the need for mouth-to-mouth resuscitation will encourage more bystanders who witness cardiac arrest to engage in resuscitation efforts, thereby saving more lives. A recent paper in the Journal of the American College of Cardiology reviewed the state of the art regarding CCR.

CCR has been gaining favor since its introduction in November 2003 in Tucson, AZ. By 2007, CCR was widely used throughout the state. The 2005 American Heart Association (AHA) guidelines incorporated some of the changes made with CCR, and a 2008 AHA science advisory statement supported chest compressions only for bystander response to adult cardiac arrest, wrote Gordon A. Ewy, MD, and Karl B. Kern, MD, of the University of Arizona College of Medicine in Tucson.

CCR has 3 components: (1) continuous chest compressions for bystander resuscitation; (2) a new emergency medical services algorithm; and (3) aggressive postresuscitation care. For advanced cardiac life support, either prompt or delayed defibrillation should be used based on the 3-phase time-sensitive model of ventricular fibrillation developed by Weisfeldt and Becker. Endotracheal intubation is delayed, excessive ventilations are avoided, and early administration of epinephrine is advocated.

CCR has dramatically improved survival by 250% to 300% in patients with witnessed arrest and a shockable rhythm—the subset of patients most likely to survive. More aggressive postresuscitation care, including hypothermia, emergent cardiac catheterization, and percutaneous coronary intervention, is required to save even more victims of cardiac arrest, the authors noted.

CCR is not recommended for individuals with respiratory arrest; these individuals should receive currently recommended CPR.


Ewy GA, Kern KB. Recent advances in cardiopulmonary resuscitation: cardiocerebral resuscitation. J Am Coll Cardiol. 2009;53(2):149-157.

Prehospital electrocardiograms may reduce mortality in patients with STEMI

The use of prehospital electrocardiograms (ECGs) during emergency medical services (EMS) transport to the hospital was associated with increased use of reperfusion therapy, faster reperfusion times, and a suggested trend toward lower mortality in patients with acute ST-segment elevation myocardial infarction (STEMI). Despite these previously reported benefits of prehospital ECGs, only slightly more than one quarter of patients received one in 2007, according to a study of STEMI patients based on a large national database registry.

“These data provide contemporary evidence supporting a more widespread use of prehospital ECGs as a key triage tool for patients with ischemic symptoms and suspected STEMI who are first evaluated by EMS,” wrote Deborah B. Diercks, MD, University of California Davis Medical Center, and colleagues, in an article in the January 2009 issue of the Journal of the American College of Cardiology.

Hospitals in the United States fall short of meeting recommended benchmarks for the timing of reperfusion therapy for patients with STEMI. Prehospital ECGs have been endorsed by the American Heart Association as a means of shortening reperfusion time, either door-to-needle (DTN) time for reperfusion therapy or door-to-balloon (DTB) time for percutaneous coronary intervention (PCI).

The present study evaluated patients with STEMI from the NCDR (National Cardiovascular Data Registry) ACTION (Acute Coronary Treatment and Intervention Outcomes Network) registry who were transported by EMS in 2007. Of 12,097 patients with STEMI, 7098 (58.7%) were transported by EMS. These patients tended to be older, female, have a history of myocardial infarction or congestive heart failure (CHF), CHF signs on presentation, and shorter times from symptom onset to hospital presentation compared with patients who transported themselves to ACTION-participating hospitals.

Of those transported by EMS, 1941 (27.4%) were given a prehospital ECG. These patients tended to be men and were less likely to have diabetes and left bundle branch block or signs of CHF on presentation compared with patients with an in-hospital ECG.

Patients with a prehospital ECG were more likely to undergo primary PCI and less likely to receive no reperfusion therapy compared with those who had an in-hospital ECG. Those with a prehospital ECG were also more likely to receive recommended antithrombolytic therapy within the first 24 hours. Both DTN and DTB times were shorter in patients who received a prehospital ECG, with decreases of 24.9% and 19.3%, respectively, when compared with those who had an in-hospital ECG. A trend toward reduced risk of adjusted in-hospital mortality, CHF, and shock was seen among those who had a prehospital ECG. No difference in adjusted risk of mortality was seen with prehospital ECG use among those who received any reperfusion therapy.

The authors cited several limitations of the study, including lack of some clinical measurements for patients who received a prehospital ECG; no data on how the prehospital ECGs were interpreted and how the results were transmitted to the ACTION-participating hospital prior to the patient’s arrival; what the impact was of the prehospital ECG on activating the catheter lab; and whether patients were diverted from a community hospital to an ACTION-participating hospital based on prehospital ECG results. Additionally, no central core lab interpreted the ECG findings and no information was collected regarding the accuracy of the EMS providers’ interpretation of the prehospital ECGs.


Diercks DB, Kontos M, Chen AY, et al. Utilization and impact of pre-hospital electrocardiograms for patients with acute ST-segment elevation myocardial infarction. J Am Coll Cardiol. 2009;53(2):161-166.

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