World No Tobacco Day

World No Tobacco Day is observed around the world every year on May 31. The member states of the World Health Organization created World No Tobacco Day in 1987. It draws global attention to the tobacco epidemic and to the preventable death and disease it causes. It aims to reduce the 3.5 million yearly deaths from tobacco related health problems.

History

• In 1987, the World Health Assembly passed Resolution WHA40.38, calling for April 7, 1988 to be "a world no-smoking day."
• In 1988, Resolution WHA42.10 was passed, calling for the celebration of World No Tobacco Day, every year on 31 May.

The health effects of tobacco smoking refer to direct tobacco smoking as well as the inhalation of environmental or secondhand tobacco smoke. The WHO in the 2002 World Health Report estimates that in developed countries, 26% of male deaths and 9% of female deaths can be attributed to smoking. Similarly, the United States'

Centers for Disease Control and Prevention describes tobacco use as "the single most important preventable risk to human health in developed countries and an important cause of premature death worldwide".

Primary risks

The main health risks in tobacco pertain to diseases of the cardiovascular system, in particular smoking being a major risk factor for amyocardial infarction (heart attack), diseases of the respiratory tract such as Chronic Obstructive Pulmonary Disease (COPD) and emphysema, and cancer, particularly lung cancer and cancers of the larynx and mouth. Prior to World War I, lung cancer was considered to be a rare disease, which most physicians would never see during their career. With the postwar rise in popularity of cigarette smoking came a virtual epidemic of lung cancer.

Incidence of impotence is approximately 85 percent higher in male smokers compared to non-smokers, and it is a key cause of erectile dysfunction (ED). Smoking causes impotence because it promotes arterial narrowing. Tobacco related illnesses kill 440,000 USA citizens per year, about 1,205 per day, making it the leading cause of preventable death in the U.S. A person's increased risk of contracting disease is directly proportional to the length of time that a person continues to smoke as well as the amount smoked. However, if someone stops smoking, then these chances gradually decrease as the damage to their body is repaired.

Diseases linked to smoking tobacco cigarettes include:

• Most forms of cancer, particularly lung cancer, cancer of the kidney, cancer of the larynx and head and neck, bladder, esophagus, pancreas, and stomach. There is some evidence suggesting an increased risk of myeloid leukemia, squamous cell sinonasal cancer, liver cancer, cervical cancer, colorectal cancer after an extended latency, childhood cancers and cancers of the gall bladder, adrenal gland and small intestine.
• Cardiovascular diseases
• Stroke
• Respiratory ailments such as the common cold and bronchitis
• Peripheral vascular diseases
• Birth defect of pregnant smokers' offspring
• Buerger's disease (thromboangiitis obliterans)
• Impotence
• Chronic obstructive pulmonary disease, emphysema and chronic bronchitis in particular
• More likely to develop cataracts that may cause blindness
• Reduced memory and cognitive abilities in adolescent smokers (Biol Psychiatry. 2005 Jan 1;57(1):56-66)

Ambulatory Arterial Stiffness Index

Ambulatory Arterial Stiffness Index Is Not a Specific Marker of Reduced Arterial Compliance

Giuseppe Schillaci; Gianfranco Parati; Matteo Pirro; Giacomo Pucci; Massimo R. Mannarino; Laura Sperandini; Elmo Mannarino
From the Unit of Internal Medicine (G.S., M.P., G.Pucci, M.R.M., L.S., E.M.), Angiology and Arteriosclerosis, University of Perugia, Perugia, Italy; the Department of Clinical Medicine and Prevention (G.Parati), University of Milano-Bicocca, Milan, Italy; and the Department of Cardiology (G.Parati), San Luca Hospital, IRCCS, Istituto Auxologico Italiano, Milan, Italy

Ambulatory arterial stiffness index (AASI), a measure based on the relative behavior of 24-hour systolic and diastolic blood pressure (BP), has been suggested as a marker of arterial stiffness and a predictor of cardiovascular mortality.

However, a narrow range of diastolic BP values over the 24 hours tends to flatten the regression slope and to artificially increase AASI. We explored the possible influence of different ranges of 24-hour diastolic BP fluctuations, such as those related to nocturnal BP fall, on AASI, and on its relationship with target organ damage. In 515 untreated hypertensive patients, AASI was directly related to age (r=0.30) and 24-hour systolic BP (r=0.20), whereas it was inversely related with nocturnal systolic and diastolic BP reduction (r=–0.28 and –0.46, respectively; all P<0.001). r="0.17;" r="0.28;">

Our conclusions are as follows: (1) AASI is strongly dependent on the degree of nocturnal BP fall in hypertensive patients; (2) there is no significant relation between AASI and left ventricular mass after proper adjustment for confounders; and (3) the relation between AASI and a widely accepted measure of aortic stiffness, such as pulse wave velocity, is weak and importantly affected by other factors.

Key Words: ambulatory blood pressure monitoring • arteries • blood pressure • arterial stiffness • left ventricular hypertrophy

Hypertension. 2007;49:986.

© 2007 American Heart Association, Inc.

Hypertension - Smoking: Impact and Cessation

Impact of Smoking and Smoking Cessation on Arterial Stiffness and Aortic Wave Reflection in Hypertension

Noor A. Jatoi; Paula Jerrard-Dunne; John Feely; Azra Mahmud
From the Department of Pharmacology and Therapeutics, Trinity College Dublin, Trinity Centre, St James’s Hospital, Dublin, Ireland.

Cigarette smoking is an important modifiable cardiovascular risk factor and pathophysiological mechanisms may include a stiff vascular tree. Although smokers have stiffer arteries, whether smoking cessation is associated with reduced arterial stiffness is not known.
We compared never-treated patients with essential hypertension (n=554) aged 18 to 80 years (56% females) classified as current smokers (n=150), ex-smokers (n=136), and nonsmokers (n=268). Ex-smokers were categorized into <1>1 and <10>10 years of smoking cessation.
Measurements included aortic stiffness, assessed as pulse wave velocity (Complior), wave reflection (augmentation index [AIx]), and transit time (TR) (Sphygmocor).
Current and ex-smokers had significantly higher pulse wave velocity and AIx compared with nonsmokers (pulse wave velocity for current smokers: 10.7±0.2; ex-smokers: 10.6±0.2; nonsmokers: 9.9±0.1 m/s; P<0.001; AIx for current smokers: 31±1; ex-smokers: 30±1; nonsmokers: 27±0.8%; P<0.05), whereas TR was lower in current and ex-smokers compared with nonsmokers (TR for current smokers: 131±1.0; ex-smokers: 135±1; nonsmokers: 137±0.8 m/s; P<0.0001).
There was a significant linear relationship between smoking status and pulse wave velocity (P<0.001), AIx (P<0.001), and TR (P<0.001), even after adjusting for age, sex, mean arterial pressure, heart rate, and body mass index.
In ex-smokers, duration of smoking cessation had a significant linear relationship with improvement in pulse wave velocity (P<0.001), AIx (P<0.001), and TR (P<0.001), with arterial stiffness parameters returning to nonsignificant levels after a decade of smoking cessation.

Key Words: smoking • arterial stiffness • pulse wave velocity • augmentation index • hypertension • smoking cessation

Hypertension. 2007;49:981.
© 2007 American Heart Association, Inc
http://hyper.ahajournals.org/cgi/content/abstract/49/5/981

Hypertension: Gene Pathways to New Therapies

Molecular Genetics of Experimental Hypertension and the Metabolic Syndrome
From Gene Pathways to New Therapies

Michal Pravenec; Theodore W. Kurtz
From the Institute of Physiology and Center for Applied Genomics (M.P.), Czech Academy of Sciences, Prague, Czech Republic; and the Department of Laboratory Medicine (T.W.K.), University of California San Francisco

Genetic studies of human and experimental hypertension provide a means to identify key pathways that predispose individuals to increased blood pressure and associated risk factors for cardiovascular and metabolic diseases.

The pathways so identified can then serve as targets for therapeutic intervention. This article discusses genetic studies in animal models of hypertension in which specific genes have been identified that regulate blood pressure and biochemical features of the metabolic syndrome.

Consistent with studies in humans with monogenic disorders of blood pressure regulation, studies in rat models have demonstrated that naturally occurring genetic variation in pathways regulating sodium chloride transport can contribute to inherited variation in blood pressure.

Such studies have also indicated that naturally occurring variation in genes, such as Cd36, that regulate fatty acid metabolism and ectopic accumulation of fat and fat metabolites can influence both biochemical and hemodynamic features of the metabolic syndrome and mediate the antidiabetic effects of drugs that activate the peroxisome proliferator-activated receptor . Angiotensin II receptor blockers with the ability to selectively modulate activity of peroxisome proliferator-activated receptor and expression of genes in these fat metabolism pathways may represent useful prototypes for a new class of transcription modulating drugs aimed at treating patients with hypertension and the metabolic syndrome.

Key Words: genetics • rats • inbred SHR • metabolic syndrome X • hypertension • angiotensin II type 1 receptor blockers • peroxisome proliferator-activated receptors

Hypertension. 2007;49:941.

© 2007 American Heart Association, Inc

Fontan Conversion - Effective Alternative

Fontan Conversion Still An Effective Alternative

Fontan conversion accompanied by arrhythmia surgery and pacemaker implantation remains a safe and effective alternative to cardiac transplantation for patients with failing Fontan circulation, Dr. Constantine Mavroudis reported at the annual meeting of the Society of Thoracic Surgeons.
During the past several years patients with failing Fontans have been presenting at an older age, with more complex lesions and more-difficult-to-manage atrial arrhythmias as the increasing popularity of transcatheter ablation procedures has delayed surgical referral.
Yet results remain excellent due to evolution in surgical techniques and advances in pacemaker therapy, said Dr. Mavroudis, the Willis J. Potts Professor of Surgery at Northwestern University and surgeon-in-chief at Children's Memorial Hospital, Chicago.
His retrospective study examined 111 consecutive patients who underwent atriopulmonary to total cavopulmonary artery extracardiac Fontan conversion at the hospital since late 1994.
The patients' mean age was 23 years, with a mean 14-year interval between Fontan and Fontan conversion. Fourteen patients had undergone prior Fontan revisions.
Dr. Mavroudis divided the experience into three periods based upon changes in arrhythmia surgery techniques.
The first epoch consisted of simple isthmus cryoablation, a strategy abandoned after nine patients.
The next 51 had right atrial maze procedures for right atrial reentry tachycardia.
The most recent 51 patients—those treated since 2003—have routinely received the more elaborate biatrial Cox maze-III procedure, which incorporates cryoablation of the left atrium. This change occurred in response to a shift in the predominant presenting arrhythmia from right atrial reentry tachycardia to more challenging cases of atrial fibrillation.
The classic Cox maze-III was supplemented with one additional cryoablation lesion running between the bases of the right and left atrial appendages and across the dome of the atria to reduce the incidence of postoperative atrial tachycardia.
There were one early and six late deaths among the 111 patients. Six patients required cardiac transplantation, with two of the six late deaths in the series coming 4 and 24 days post transplantation. The other four donor heart recipients are alive 5–7 years later.
With follow-up extending to 12 years, 88% of patients have experienced an improvement in New York Heart Association functional class. The arrhythmia recurrence rate was 13.5% overall, declining to just 8% in the most recent group comprised of 51 Cox maze-III-treated patients.
Postoperative arrhythmia recurrence in patients with preoperative refractory atrial fibrillation took the form of atrial tachycardia, Dr. Mavroudis continued, which is far more easily treated.
In a multivariate analysis, the strongest risk factor for death or transplantation was protein-losing enteropathy, present preoperatively in three patients and associated with an 87-fold increased risk.
A right or ambiguous ventricle and preoperative moderate to severe atrioventricular valve dysfunction also predicted poor outcome.
Discussant Dr. Joseph A. Dearani praised Dr. Mavroudis for heading what the congenital heart disease surgery community recognizes to be the world's premier Fontan conversion program.
“The most important contribution from their experience is the thorough understanding of the different atrial arrhythmias that occur in the failing Fontan circulation and their methods of ablation, which have evolved over time,” observed Dr. Dearani, a cardiothoracic surgeon at the Mayo Clinic, Rochester, Minn.
“The importance of the need to address both atria at the time of operation cannot be overemphasized,” he added.
Noting that the late deaths and cardiac transplantations in the Chicago series all occurred relatively early—within a year after Fontan conversion—Dr. Dearani asked whether it might make more sense to consider protein-losing enteropathy, significant atrioventricular valve regurgitation, and severe ventricular dysfunction to be contraindications to Fontan conversion and instead send affected patients directly to heart transplantation.
Dr. Mavroudis, however, answered that he would not yet include atrioventricular valve regurgitation as a contraindication. This is because his recent experience using Alfieri valvuloplasty has, so far, been very encouraging.
At 12 years follow-up, 88% of patients saw an improvement in New York Heart Association functional class. DR. MAVROUDIS

Cardiology News, Volume 5, Issue 4, Page 28 (April 2007)

Metabolic Syndrome and CAD in Women

Link Between Metabolic Syndrome, Coronary Artery Disease in Women Is Weak

Despite having a higher incidence of metabolic syndrome, women had less obstructive coronary artery disease in a study of 468 patients who presented for elective cardiac catheterization.

Nondiabetic women were significantly more likely to have metabolic syndrome than were their nondiabetic male counterparts (52% vs. 28%), although nondiabetic men had a significantly greater percentage of coronary artery disease (CAD) (42% vs. 18%). Dr. Andrew Weissman and colleagues from Lenox Hill Hospital in New York City reported their findings in a poster at the Southern regional meeting of the American Federation for Medical Research.

The results call into question whether lower cutoffs should be used to identify metabolic syndrome in women or whether the presence of metabolic syndrome itself is truly a risk factor for coronary artery disease, Dr. Weissman said in an interview.

“The goal of identifying metabolic syndrome is to try to pick out those people with a higher risk for coronary artery disease and it doesn't seem to be doing that in nondiabetic females according to the results of our study,” he said.

The study included 277 men (mean age 60 years) and 191 women (mean age 63 years) with no known history of coronary artery disease. Metabolic syndrome was evaluated using the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) criteria.

The NCEP criteria recommend that metabolic syndrome be identified if three or more of the following risk factors are present: waist circumference of 102 cm or greater in men and 88 cm or greater in women; elevated triglyceride level of 150 mg/dL or greater; reduced HDL cholesterol level of less than 40 mg/dL in men and less than 50 mg/dL in women; elevated blood pressure of 135/85 mm Hg or greater; and an elevated fasting glucose of 110 mg/dL or greater.

Diabetes mellitus was present in 79 men (28.5%) and 49 women (25.6%). The difference between gender groups was not statistically significant, the investigators reported.
Metabolic syndrome was present in 233 of 468 patients and was found in a significantly higher percentage of women (62%) than men (41%).

Coronary artery disease, defined as the presence of 70% or greater stenosis in one of the three major coronary vessels or 50% stenosis in the left main coronary artery, was present in 48 (25%) women, compared with 132 (48%) men.

There was no significant difference between patients with and without metabolic syndrome with regard to mean Framingham risk score or for age, tobacco use, or family history of coronary artery disease, said Dr. Weissman, a third-year cardiology fellow at Lenox Hill Hospital.

However, both men and women with diabetes were significantly more likely to have CAD than were their nondiabetic counterparts.

There was no significant difference in percentage of coronary artery disease between men and women with diabetes (62% vs. 45%). There was a trend toward women with diabetes being more likely to have metabolic syndrome than were men with diabetes (90% vs. 75%), but it was not statistically significant, the authors wrote.

Although diabetes is considered a coronary risk equivalent, the independent significance of metabolic syndrome in practice remains controversial.

“The clinical implication is that our study results do not support the use of metabolic syndrome as a useful risk stratifier for coronary artery disease,” Dr. Weissman said.

Cardiology News, Volume 5, Issue 4, Page 20 (April 2007)

Prevent stent thrombosis

Intravascular Ultrasound Use in Stent Placement May Prevent Thrombosis

The use of intravascular ultrasound to guide the placement of drug-eluting stents may help to prevent stent thrombosis, according to findings from a review of a large database of lesions.

Lack of intravascular ultrasound (IVUS) guidance was the only significant independent predictor of stent thrombosis in a series of 5,066 native and coronary bypass graft lesions treated with the Cypher sirolimus-eluting stent or the Taxus paclitaxel-eluting stent since April 2003, Dr. Probal Roy reported during a poster session at a symposium jointly sponsored by the Washington Hospital Center and the Cardiovascular Research Institute.

The Cypher stent was approved by the Food and Drug Administration in that month, and the Taxus stent was approved in March 2004.

A total of 62 of these stented lesions presented with stent thrombosis within 1 year of their initial implantation, according to Dr. Roy of the division of cardiology at the Washington Hospital Center.
Lesions for which IVUS was used to guide drug-eluting stent placement were 58% less likely to develop stent thrombosis than were those for which IVUS was not used, according to a multivariate logistic regression analysis.

The investigators defined stent thrombosis as any partial or complete stent occlusion with or without the presence of thrombosis on angiography or autopsy.

“The use of IVUS to ensure excellent stent expansion and apposition should be considered during [drug-eluting stent] implantation in an attempt to prevent stent thrombosis,” the investigators suggested.

Cardiology News, Volume 5, Issue 4, Page 12 (April 2007)

Coronary Artery Disease: Diabetes and Depression

Diabetes Plus Depression May Raise Mortality in Coronary Artery Disease Patients

Having both type 2 diabetes and depression puts patients with coronary artery disease at greater risk of death over a 4.5-year period than does either condition alone.

The more severe the depressive symptoms were in those patients with both coronary artery disease and diabetes, the greater their risk of death in the follow-up period.

The finding suggests that physicians should screen for and treat depression in their patients with diabetes and heart disease, said Anastasia Georgiades, Ph.D., at the American Psychosomatic Society meeting in Budapest, Hungary.

Having high scores on the Beck Depression Inventory increased the risk of dying during the follow-up period by 20%–30%, compared with those patients who had similar depression scores but without type 2 diabetes, according to the investigators.

Researchers from Duke University, Durham, N.C., compared 325 patients with type 2 diabetes and 582 patients without the disease during hospitalization for a coronary angiography.
Their depression symptoms were rated using the Beck Depression Inventory (BDI). Approximately 25% scored at least 10 on the BDI, indicating depression, Lana Watkins, Ph.D., an investigator in the study, noted in an interview.

During the study's follow-up period of 4.5 years (median, 3 years), there were 135 deaths among the study participants. Among the depressed group of patients, 19% died, compared with 12% of those participants who did not have depression, Dr. Watkins said.

The researchers found statistically significant associations between depressive symptoms and increased mortality and, separately, diabetes and increased mortality.
The highest mortality was among patients with both diabetes and elevated BDI scores.
The researchers did not publicize hazard ratios, however, because they said those statistics would overestimate the risk and could also create anxiety among patients.

“There is some sort of synergistic effect between type 2 diabetes and depression that we don't fully understand,” Dr. Georgiades said in a statement. “In our analysis, we controlled for factors that could influence mortality, such as heart disease severity and age. For whatever reasons, these patients were still at higher risk of dying, and future research will aim to investigate the mechanisms for this association.”

“Patients with type 2 diabetes typically have an extensive self-care regimen involving special diet, medications, exercise, and numerous appointments with their doctor,” Dr. Georgiades said in the statement.
“It may be that such patients who are depressed might not be as motivated to carry out all these activities, thereby putting them at higher risk,” she added.

“Regular exercise has been shown to improve depression, too, so that might be an option,” Dr. Watkins noted in an interview. “This could potentially improve depression and diabetes, and might be a good first choice for diabetics who would prefer not having to take additional medications.”

Cardiology News, Volume 5, Issue 4, Page 20 (April 2007)

Acute coronary syndrome and new-onset diabetes

Novel Drug Prevented New-Onset Diabetes, Cut Major Events

Succinobucol, a novel antioxidant with anti-inflammatory properties, achieved a 64% reduction in new-onset diabetes in patients with a recent acute coronary syndrome in the phase III Aggressive Reduction of Inflammation Stops Events (ARISE) trial.
Use of the investigational agent also was linked to significant reductions in cardiovascular death, MI, and stroke, compared with optimal current therapy in the 6,144-patient double-blind randomized trial, Dr. Jean-Claude Tardif reported at the annual meeting of the American College of Cardiology.
But these were prespecified secondary outcome measures. Succinobucol failed to achieve a significant impact on the primary end point, a composite of “hard” atherosclerotic outcomes and the “soft” end points of coronary revascularization and hospitalization for unstable angina, said Dr. Tardif, professor of medicine at the University of Montreal and director of research at the Montreal Heart Institute.
That failure was severely punished by a single-day 60% nosedive in the stock price of AtheroGenics Inc., the trial sponsor, as some observers dismissed ARISE as a negative study. That's not how the ARISE investigators see it, though.
“I'm pretty bullish,” added Dr. Marc A. Pfeffer, ARISE coprincipal investigator. “We're all looking for the next step [in cardiovascular risk reduction], and I think this is as promising as anything I've seen in terms of developments.
“We didn't hit our primary end point, but we're the ones who established that primary. We made it more inclusive. We wish we hadn't, we wish we'd made it the firmer one, but there it is. The firm end points are there, and the diabetes effect was pretty profound. If we can come back here with another study aiming specifically at those end points and we can show positive results, then that would be the highest compliment for a clinical trial—it would change the practice of medicine. That's our aim,” said Dr. Pfeffer, professor of medicine at Harvard Medical School, Boston.
The 6,144 ARISE participants were randomized to 300 mg/day of succinobucol or placebo for an average of 2 years starting shortly after hospitalization for an acute MI or unstable angina. All were deemed at high risk for further atherosclerotic events. Rates of utilization of secondary preventive therapies were extremely high: 90% of patients were on a statin at baseline, 80% on a β-blocker, 92% on aspirin, and 74% on an ACE inhibitor or angiotensin receptor blocker.
A total of 37% of subjects had diabetes at baseline, with a mean HbA1c of 7.2%. Among the other nearly 4,000 participants, the incidence of new-onset diabetes was 4.2% with placebo and 1.6% with succinobucol, a 64% relative risk reduction. Consistent with this benefit, succinobucol resulted in a mean 0.5% lower HbA1c than placebo did at 12 months in patients with diabetes at entry, and an improvement in fasting blood glucose as well.
The combined “hard” secondary atherosclerotic end point of cardiovascular death, cardiac arrest, MI, or stroke occurred in 8.2% of the placebo group and 6.7% with succinobucol, for a significant 19% relative risk reduction.
The chief side effect of succinobucol was diarrhea, reported by 23% of patients, although only one in seven of those affected discontinued the study. The incidence of liver function abnormalities was similar to that with placebo.
Discussant Dr. Robert A. Harrington, director of cardiovascular clinical trials at the Duke Clinical Research Institute, Durham, N.C., said ARISE sends mixed signals, including unwelcome trends toward increased heart failure hospitalizations, lower HDL, and increased LDL.
Succinobucol, a potent lipophilic antioxidant, is the monosuccinic acid ester of probucol. The drug's appeal, Dr. Pfeffer said, lies in the fact that it operates by mechanisms beyond modification of the conventional risk factors such as blood pressure and lipids.
Officials at AtheroGenics indicated they plan to back a large confirmatory trial.
Dr. Tardif and Dr. Pfeffer disclosed that their financial relationship with AtheroGenics is limited to research grants.

Cardiology News, Volume 5, Issue 4, Page 5 (April 2007)

Decompensated Heart Failure: Novel Drug

Novel Drug Eases Symptoms of Heart Failure

The investigational agent tolvaptan relieves core symptoms of acute decompensated heart failure (HF) without inducing adverse effects, but has no impact on all-cause mortality, according to researchers in the EVEREST clinical trials.

The oral vasopressin antagonist also had no effect on the combined end point of cardiovascular mortality or subsequent hospitalization for worsening heart failure, study investigators reported at the annual meeting of the American College of Cardiology.

One day into therapy, after one dose, significantly more patients reported improvement in dyspnea scores after taking tolvaptan, compared with placebo. Changes in body weight due to improvements in fluid overload were also significant at day 1 and day 7 of therapy, and were sustained during a median 9.9 months of follow-up, study investigator Dr. Marvin A. Konstam reported at the meeting.

“I, as a clinician, can say I have something new to offer patients,” said Dr. Konstam, chief of cardiology and professor of medicine at Tufts-New England Medical Center, Boston, in a press conference.
However, Dr. Konstam acknowledged he was “disappointed” that the agent failed to reduce mortality or heart failure-related morbidity either during hospitalization or at 1-year follow-up.

In an editorial accompanying simultaneous publication of trial data, Dr. Clyde W. Yancy of Baylor Heart and Vascular Institute, Dallas, applauded the “noteworthy findings” on symptomatic improvement, but said the lack of impact on global clinical status, subsequent hospitalizations, or mortality must temper enthusiasm for the EVEREST findings.

“To the extent that it helps patients do better, that's a good thing,” said Dr. Yancy at the ACC press conference. He called the lack of safety signals in the follow-up study “comforting.”
But neither physician suggested that the trial points to an improvement in the progression of heart disease in a patient group Dr. Konstam termed “daunting.”
He specifically said it should not be used indiscriminately or indefinitely in patients with worsening heart failure, although he said he might reinstate it if a patient's fluid overload worsened upon discontinuation of short-term use of the drug.

The Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial comprised two identical short-term trials (required to meet regulatory requirements for two independent confirmatory studies) and one long-term safety trial. All were conducted at 359 sites in North America, South America, and Europe between 2003 and 2006, and all were funded by Otsuka Inc., the drug's manufacturer.
In the two short-term trials, the clinical effects of tolvaptan were compared with those of placebo when added to optimal medical therapy during hospitalization for acute decompensated heart failure (HF) with impaired left ventricular ejection fraction (LVEF). In trial A, 1,018 subjects were randomly assigned to receive tolvaptan and 1,030 to receive placebo, while in trial B the numbers were 1,054 and 1,031, respectively, wrote Dr. Mihai Gheorghiade of Northwestern University, Chicago, and associates (JAMA 2007;297:1332–43).

In both short-term trials, patients in the active drug group showed decreases in body weight as early as the first day of treatment, which persisted as long as the drug was administered (7 days or until hospital discharge, whichever came first). Dyspnea and rales, fatigue, jugular venous distension, and pedal edema all improved in a similar fashion.
Tolvaptan improved or normalized serum sodium concentrations in hyponatremic patients. It also allowed all patients to reduce their use of furosemide.

“These positive effects were achieved without adversely affecting heart rate, blood pressure, or serum electrolytes,” and there was no adverse effect on liver or renal function, the investigators wrote.
The long-term trial was primarily designed to assess the drug's safety in the same patients from hospital discharge through 1-year of follow-up. Unlike other agents previously used to treat the disorder, “Long-term tolvaptan treatment had no effect, either favorable or unfavorable, on all-cause mortality or the combined end point of cardiovascular mortality or subsequent hospitalization for worsening HF,” wrote Dr. Konstam, the lead investigator in this trial, and his associates.

“Overall, the benefits on short-term symptoms, together with the demonstrable short-term and long-term safety profile, support the usefulness of tolvaptan treatment for patients manifesting volume overload during hospitalization for HF,” they wrote (JAMA 2007;297:1319–31).
Tolvaptan's safety record stands in contrast to nesiritide, which has been associated with increased mortality and renal dysfunction two meta-analyses.

In his editorial comment, Dr. Yancy noted that in the short-term trials, improvements in dyspnea and edema with tolvaptan were “modest” relative to placebo and were mainly driven by decreases in body weight. There were no differences in global clinical status, nor in rates of recurrent HF hospitalization or mortality. And rates of adverse events—especially thirst and dry mouth—were “high” in all three EVEREST trials, he said.
Moreover, the trial results apply only to patients with profiles like those of the study subjects, and cannot be extrapolated to other groups such as heart failure patients with preserved left ventricular ejection fraction and nonhospitalized heart failure patients.

Cardiology News, Volume 5, Issue 4, Page 1,7 (April 2007)

Novel Antiangina Drug

Novel Antiangina Drug Studied in Diabetes

The novel selective serotonin 2A receptor antagonist sarpogrelate produces numerous physiologic benefits in type 2 diabetic patients with stable angina, Dr. Hideki Watanabe said at the annual scientific sessions of the American Heart Association.
The investigational agent has shown promise as an antianginal drug in preliminary clinical studies. But this was not the focus of Dr. Watanabe's 30-patient, 12-month randomized trial, designed instead to examine the mechanisms involved in sarpogrelate's antianginal effects.
In the study, sarpogrelate at 300 mg/day significantly improved vascular endothelial function, aortic stiffness, and exercise tolerance. Moreover, it also reduced insulin resistance, systemic inflammation, and markers of oxidative stress. All these benefits were maintained through the full 12 months of the study, said Dr. Watanabe of the Kunu Medical Association Hospital, Joso, Japan.
Levels of high-sensitivity C-reactive protein in the sarpogrelate group fell from 1.02 mg/dL at baseline to 0.51 mg/dL at 6 months and 0.30 mg/dL at 12 months while remaining unchanged in controls. Insulin resistance as estimated by homeostasis model assessment fell from 5.7 at baseline to 3.2 at 1 year, with no significant change in controls. Exercise tolerance as reflected in time to a 0.10-mV ST-segment depression on a Bruce treadmill protocol rose from 345 seconds at baseline to 490 seconds in the sarpogrelate group and 360 seconds in controls.
Most participants in the study, sponsored by Mitsubishi Pharma, were on a calcium channel blocker, a β-blocker, and nitroglycerin for angina control, Dr. Watanabe said.

Cardiology News, Volume 5, Issue 3, Page 36 (March 2007)

Hypertension: first step in preventing

Weight Loss in Prehypertension Cuts Risks, Helps Avoid Medication

Prehypertensive patients who participate in a structured weight-management program can significantly cut their risk factors and may avoid the need for drug therapy, according to a study presented at the annual meeting of NAASO, the Obesity Society.

A group of 351 patients who enrolled in various weight-loss programs had a mean baseline bloody pressure (BP) of 127/83 mm Hg. Over an average follow-up period of just under 3 years, these readings fell to a mean of 119/74 mm Hg, reported Linda Grant of Health Management Resources (HMR), Boston.

Mean weight at baseline was 231 pounds (104,78 kg). During the follow-up period, this fell to 194 pounds (88,00 kg), representing an average of 16% of initial body weight lost.

None of the patients was taking antihypertensive medications at baseline, and about 94 remained medication free throughout the study.

Patients in this cohort also had significant decreases in all other measured risk factors. Total cholesterol levels fell by an average of 14%, triglycerides decreased by 30%, and fasting blood glucose was lowered by 5%, Ms. Grant wrote in a poster session. “Lifestyle changes, including weight management, should be the first step in preventing or delaying the progression of prehypertension to hypertension and in reducing other comorbid risk factors,” she wrote.

The weight-management options offered by HMR include medically supervised low- and very-low-calorie diets, moderately restricted diets, and telephone-based programs. All of the options focus on lifestyle changes such as increased physical activity to an expenditure of 2,000 kcal/week or more, the use of meal replacements, and increased fruit and vegetable intake to 35 servings/week or more.

In another study undertaken by HMR, Steve May, Ph.D., reported that program participants who lost 20% or more of their body weight had greater decreases in risk factors than did those who lost smaller amounts of weight.

Among 2,564 patients who had participated in the HMR weight-management programs at 65 clinics natiowide, those who lost the most weight—and kept it off for an average time of 123 weeks—also showed significant decreases in all other measured risk factors.

Moreover, a significant percentage of patients were able to eliminate medications for cholesterol, BP, and diabetes, Dr. May wrote.

Cardiology News, Volume 5, Issue 3, Page27 (March 2007)
http://www.ecardiologynews.com/article/PIIS1544880007701185/fulltext

Sleep Apnea and Hypertension

Sleep Apnea and HT Tied in Kidney Disease

Hypertension is associated with a significantly increased prevalence of sleep apnea among patients with chronic kidney disease, Dr. Stephen F. Derose reported at a meeting of the American Heart Association Council for High Blood Pressure Research.

The clinical implication of this finding is that comorbid hypertension in patients with chronic kidney disease (CKD) of any stage—including stage 1, marked by a normal glomerular filtration rate (GFR) plus proteinuria—might reasonably lower the threshold for screening for sleep apnea, added Dr. Derose of Kaiser Permanente Medical Center, Los Angeles.

There has been speculation that exposure to repeated hypoxic episodes as a result of comorbid sleep apnea accelerates damage to the kidney and increases mortality risk in CKD patients.
But since it would be a daunting task to screen everyone with CKD for sleep apnea, Dr. Derose and his colleagues set about to learn whether the presence of hypertension might be a useful factor in deciding which patients with CKD should be aggressively screened for the disorder.

In this large, cross-sectional observational study, he reported on nearly 721,000 adult Southern California enrollees in the Kaiser Permanente health plan with at least two GFR measurements during 2000–2004. Nearly 396,000 had a GFR greater than 90 mL/min per 1.73 m2 and no proteinuria. The prevalence of diagnosed hypertension in this group was 28%, while 2.1% had received the diagnosis of sleep apnea. Of those with sleep apnea, 51% also had hypertension.

Patients with stage 1 CKD presented a very different picture. The prevalence of hypertension in this group of just under 5,000 patients was 74%. The prevalence of sleep apnea was 5.3%. And 87% of those with sleep apnea were hypertensive.

In patients with stage 2–4 CKD, the prevalence of comorbid hypertension rose from 55% with stage 2 disease to 94% in stage 4. The prevalence of apnea remained steady at about 3.3%. In patients with sleep apnea, the prevalence of hypertension rose from 66% in stage 2 CKD to 86% in stage 3 and 100% in stage 4.

Exposure to repeated hypoxic episodes as a result of comorbid sleep apnea may accelerate damage to the kidney. DR. DEROSE

Cardiology News, Volume 5, Issue 3, Page 27 (March 2007)

Pediatric Hypertension: Sleep-Disordered Breathing

Pediatric Hypertension Is Linked To Sleep-Disordered Breathing

SAN ANTONIO — Hypertension in children and adolescents may constitute a novel risk factor for sleep-disordered breathing, Dr. Alisa A. Acosta said at a meeting of the American Heart Association Council for High Blood Pressure Research.

“At this point, there is no indication to refer patients with only hypertension for a sleep study. However, our study does reinforce recommendations from the National Heart, Lung, and Blood Institute's working group for blood pressure in children and adolescents to screen for sleep-disordered breathing risk factors in pediatric patients with systemic hypertension, especially if they're obese.” according to Dr. Acosta of the University of Texas, Houston.

At the university's pediatric hypertension clinic, physicians have begun routinely screening hypertensive patients for sleep-disordered breathing (SDB) risk factors and symptoms. If positive for even one, the patient is referred for a sleep study, as were 26 of the last 350 (7%) screened patients.

Of those 26 patients (mean age 12.6 years), 20 actually underwent overnight polysomnography, of whom 12 (60%) proved to have some form of SDB. Eight patients had obstructive sleep apnea, defined as more than one obstructive apnea episode per hour. Three patients had obstructive hypoventilation, diagnosed by a maximum PCO2 greater than 53 torr during sleep and/or greater than 50 torr during more than 10% of sleep.

One patient had hypopnea, marked by a greater than 50% reduction in airflow with a 4% decrease in oxygen saturation and/or a 25% drop in heart rate.

In contrast to the observed 60% prevalence of SDB in this study, the prevalence in the general pediatric population has been estimated at 2%–3%.

Cardiology News, Volume 5, Issue 3, Page 27 (March 2007)
http://www.ecardiologynews.com/article/PIIS1544880007701197/fulltext

Women's Lifetime Risk

Heart Guidelines Stress Women's Lifetime Risk

Elizabeth Mechcatie (Senior Writer)

The American Heart Association's new evidence-based guidelines for preventing cardiovascular disease (CVD) in women emphasize a woman's lifetime risk and provide new recommendations on aspirin, folic acid, antioxidants, and hormone therapy.

The updated guidelines are the most current clinical recommendations for preventing CVD in women ages 20 and older, addressing the primary and secondary prevention of chronic atherosclerotic vascular diseases. The recommendations are based on “a systematic search of the highest quality science, interpreted by experts in the fields of cardiology, epidemiology, family medicine, gynecology, internal medicine, neurology, nursing, public health, statistics, and surgery,” according to the authors, an expert panel. The guidelines will be published in the March 20 issue of Circulation.

The guidelines place a greater emphasis on a woman's lifetime risk of CVD, rather than on the short-term risk, as in the previous guidelines, issued in 2004. The panel acknowledges that nearly all women are at risk for CVD, “which underscores the importance of a heart-healthy lifestyle.” Instead of classifying a woman as being at high, intermediate, lower, or optimal risk, the 2007 guidelines recommend classifying a woman as high risk, at risk, or optimal risk.

Part of the rationale for emphasizing lifetime risk rather than short-term risk is evidence that physicians do not make strong lifestyle recommendations for women considered low risk, said Dr. Lori Mosca, the chair of the panel that wrote the new guidelines. “Helping women understand that even though their short-term risk may not be impressive, that because heart disease and stroke are such common conditions, many risk factors can be prevented by doctors [if they stress] a more aggressive lifestyle [intervention] early on,” she said in an interview, noting that 30% of women have CVD and almost one in three women die of it.

For example, as women age, they tend to gain weight with every decade, increasing their risk for hypertension, abnormal cholesterol level, and diabetes. “If we can communicate effectively with our patients that healthy lifestyles early on will prevent the development of risk factors requiring treatment … this may be very motivational for patients,” said Dr. Mosca, director of preventive cardiology at New York-Presbyterian Hospital.

She urged physicians to link positive behaviors with outcomes that are meaningful to the patient. “What doctors can do is help women understand that their behaviors now will make a difference even in their midlife, in terms of preventing risk factors, and later in life, preventing heart disease and stroke.”

Other important differences from 2004 are the revisions regarding menopausal therapy, aspirin therapy, and folic acid, because more definitive data on these therapies have been published since that time. The guidelines state that hormone therapy and selective estrogen receptor modulation should not be used for primary or secondary prevention of CVD in women and that antioxidant supplements, such as vitamins E and C, and β-carotene, should also not be used. Folic acid, with or without B6 and B12 supplementation, should also not be used to prevent CVD.

More definitive clinical trial data are now available regarding the use of aspirin in women to prevent stroke, and the new guidelines say that “aspirin therapy should be considered for all women for stroke prevention, depending on the balance of risks and benefits.” This area is potentially a confusing one for physicians, Dr. Mosca said. The strengths of these recommendations are classified based on the levels of evidence available.

For high-risk women, aspirin therapy, at 75–325 mg/day, is recommended, unless contraindicated, in which case clopidogrel should be substituted. The recommendation for aspirin for high-risk women—such as women with diabetes or heart disease—is class I, where the intervention is considered useful and effective and should be done unless there is a reason not to, Dr. Mosca said. For other at-risk or healthy women aged 65 and older, aspirin, at 81 or 100 mg every other day, should be considered if their BPis controlled “and benefit for ischemic stroke and MI prevention is likely to outweigh” the risk of GI bleeding and hemorrhagic stroke. This regimen should also be considered in women under age 65 when the benefit for preventing ischemic stroke is likely to outweigh the risks of treatment.

For women over 65, this is a class IIa, level B recommendation, where the intervention may prevent heart disease and may prevent stroke, but the benefits should outweigh the risks, she said.

For women under 65 the evidence is very weak for stroke prevention. “It doesn't mean you can't do it … but for the majority of women under 65, the benefits of aspirin are not likely to outweigh the risks.” Dr. Mosca said in the interview. Routine use of aspirin in healthy women under age 65 should also not be used to prevent MI, with evidence that is class III (the intervention is not useful or effective and may be harmful).

An algorithm that health care providers can use to evaluate a woman's CVD risk and to prioritize preventive interventions is provided in the guidelines, as well as a list of the evidence-based clinical recommendations for preventing CVD in women, with lifestyle interventions, major risk factor interventions, and preventive drug interventions. Each recommendation comes with the strength of the recommendation and the evidence used to support the recommendation. A table listing interventions that, based on current evidence, are not useful or effective and may be harmful for preventing CVD or MI in women is also incorporated, and includes menopausal therapy.

The statement refers to a previous AHA study, which found that 36% of women did not perceive themselves to be at risk for CVD and 25% said their health care provider “did not say heart health was important.” And one in five “said their health care providers did not clearly explain how they could change their risk status.”

Other recommendations include advising women who need to lose weight or sustain weight loss to engage in moderate-intensity physical activity for 60–90 minutes on most but preferably all days of the week.

More research on the added benefits, risks, and costs of new CVD risk factors, such as high sensitivity C-reactive protein, and new screening techniques, such as coronary calcium scoring, is needed before they can be incorporated into these guidelines, according to the panel.

Members of the panel represented organizations and cosponsors, which included the AHA, the American College of Cardiology Foundation, and the National Heart, Lung, and Blood Institute.

Cardiology News, Volume 5, Issue 3, Page 1,5 (March 2007)http://www.ecardiologynews.com/article/PIIS1544880007700866/fulltext