CARDIOVASCULAR NEWS
The FRISC II substudy randomized 2457 patients with unstable coronary artery disease to an early invasive strategy with coronary angiography/revascularization within 7 days or to a non-invasive strategy with coronary procedures only when symptoms or severe ischemia recurred.
In the invasive group, 45% of the patients with ST depression had three-vessel disease or left main stenosis compared with 22% if no ST-segment depression was present, P=0.004. With early invasive strategy, mortality was reduced from 5.8 to 3.3%, P=0.050.
In patients without ST-segment depression, the corresponding rates of death/myocardial infarction were 10.4 and 8.9, and for mortality 2.0% and 1.2% (non-significant).
In unstable coronary artery disease, ST-segment depression is associated with a 100% increase in the occurrence of three-vessel/left main disease and to an increased risk of subsequent cardiac events.
In these patients an early invasive strategy substantially decreases death/myocardial infarction.
(European Heart Journal. 2002;23:41-49)
Ranolazine is a partial inhibitor of fatty acid oxidation (pFOX inhibitor).
Combination Assessment of Ranolazine In Stable Angina (CARISA) randomized 823 pts with chronic angina on background antianginal therapy of calcium blocker or beta blocker to a 3-arm parallel double-blind study of placebo, ranolazine 750, or 1000 mg bid. At 12 wks, ranolazine significantly increased exercise time (P<0.02), time to angina (P<0.004), and time to ST depression (P<0.005). Angina frequency was significantly reduced by 0.8 and 1.1 episodes/wk at 750 mg (P=0.004) and 1000 mg (P<0.0001), respectively. Minor side effects (dizziness, nausea, constipation or asthenia) were observed in <8% of pts.
Ranolazine is a new potentially effective antianginal drug for chronic angina patients who remain symptomatic on background therapy.
(Circulation. 2001;104:1B)
The Heart Protection Study assessed the effects of cholesterol-lowering therapy and of antioxidant vitamin supplementation in various patient categories for which there had been uncertainty about the value of such treatment.
Patients aged 40–80 with a history of occlusive vascular disease or diabetes were eligible provided their own doctors did not consider statin therapy clearly indicated.
Between July 1994 and May 1997, 20,536 patients were recruited in 69 UK hospitals.
There were 5082 women and 15,454 men, with 4893 aged 65–69 and 5804 aged 70–80.
Total cholesterol was <5.0 mmol/l (194 mg/dl) in 4072, and LDL cholesterol was <3.0
mmol/l (116 mg/dl) in 6793.
Participants were randomly allocated simvastatin 40 mg daily or matching placebo for 51/2 years.
Using a factorial design, half of each treatment group was also randomly allocated antioxidant vitamins (600 mg E, 250 mg C, 20 mg beta-carotene daily) and half allocated placebo.
Simvastatin 40 mg daily produced reductions in “major vascular events” of at least one-third in a very wide range of high-risk patients for whom there had previously been uncertainty about using cholesterol-lowering therapy (including women, people aged over 70, those with LDL below 3.0
mmol/l, and those with diabetes or noncoronary occlusive disease without pre-existing
CHD).
The vitamins did not produce any beneficial or adverse effects on vascular or non-vascular morbidity or mortality in this population.
(Circulation. 2001;104:1B)
A retrospective study of patients enrolled in the MOCHA trial (Multicenter Oral Carvedilol Heart Failure Assessment) showed that aspirin (ASA) blunted the improvement in left ventricular ejection fraction (LVEF) over time in patients with heart failure and systolic dysfunction treated with carvedilol.
Aspirin did not significantly affect the heart rate or systolic blood pressure response in either the placebo or carvedilol groups.
The effect of ASA became more significant on multivariate analysis.
The change in LVEF was also influenced by carvedilol dose, etiology of heart failure, baseline heart rate, EF and coumadin use.
The detrimental effect of ASA on the improvement in LVEF was dose-related and was present in both placebo and carvedilol groups, although the effect was statistically significant only in the much larger carvedilol group.
The specific mechanism(s) underlying this interaction are unknown and further studies are needed to provide additional understanding of the molecular basis of factors influencing reverse remodeling in patients with heart failure.
(J Am Coll Cardiol. 2001;38 (7):1950-1956)
The effect of adding the angiotensin-receptor blocker valsartan to standard therapy in heart failure
was evaluated in a randomized study of 5010 patients with heart failure.
Valsartan significantly reduces the combined end point of mortality and morbidity and improves clinical signs and symptoms in patients with heart failure, when added to prescribed therapy.
However, a post hoc analysis showed an adverse effect on mortality and morbidity in the subgroup receiving Valsartan an ACE inhibitor and a beta-blocker, thus raising concern about the potential safety of this specific combination.
(N Engl J Med. 2001;345:1667-1675).
Previous studies have shown an association between homocysteine levels and restenosis following coronary angioplasty.
Researchers now show that reducing homocysteine levels with folate treatment decreases the rate of restenosis and the need for future revascularization.
It is cheap, safe, and should be used.
(N Engl. J. Med. 345(22):1593-1600).
In a randomized, open-label trial (HERO-2), 17,000 patients with an acute heart attack received streptokinase and either unfractionated heparin or the thrombin-specific anticoagulant bivalirudin.
The latter group had a 30% lower rate of reinfarction within the first four days, but 30-day mortality was the same.
(Lancet 358(9296):1855-1863)
Among 309 patients having coronary bypass graft surgery, the 20% who were depressed had a cardiac event over the next year at over twice the rate of those who were not depressed.
The mood disorder’s independent effect on cardiovascular health has also been seen in the general population, in patients having coronary
angiography, and in those who have had a heart attack.
(Lancet 2001; 358: 1766-71)
In a population-based survey of 15,000 middle-aged and elderly Britons, researchers found that LDL and total cholesterol levels fell as eating frequency rose.
People who ate more than six times a day had lipid levels that were an average 10 mg/dl lower than those of people who ate only once or twice a day.
(Br. Med. J. 323(7324):1286).
Among several thousand middle-aged subjects in the Framingham Heart Study, over a third of those with high normal blood pressure became hypertensive within the next four years.
The risk was greatest for people who put on any weight; a 5% gain raised the odds for progressing to hypertension by 25%.
(Lancet 358(9294):1682-1686).
Leptin plays a role in fat metabolism and correlates with insulin resistance and other markers of the metabolic syndrome, independent of total adiposity.
In a large prospective study of 1160 men followed up for a period of 5 years, researchers found that plasma leptin levels were significantly higher among those who experienced a coronary event as compared to those with lower levels (5.87±2.04 ng/mL versus 5.04±2.09 ng/mL, P<0.001).
Leptin correlated with C-reactive protein and, even with this variable added to the model, leptin retained significance as a predictor of coronary events (RR, 1.18; 95% CI, 1.00 to 1.39; P=0.05) at the expense of C-reactive protein.
The study shows for the first time that leptin is a novel, independent risk factor for coronary heart disease.
(Circulation. 2001;104:3052).
The association of mitral annular calcification, aortic valve sclerosis, and aortic root calcification was evaluated in patients who underwent evaluation of chest pain with myocardial perfusion single photon emission computed tomography
(SPECT) and a two-dimensional transthoracic echocardiogram for other indications.
Compared with no or one calcium deposit and no or one coronary risk factor other than diabetes, multiple (˛2) calcium (or sclerosis) deposits with diabetes or multiple (˛2) coronary risk factors were significantly associated with abnormal SPECT in women age 55 years old and in men age 55 years old.
Multivariate analyses identified multiple calcium deposits as a significant predictor for an abnormal SPECT in women (p < 0.001), younger subjects age 55 years (p < 0.05) and the total group of subjects (p < 0.01).
When coronary risk factors are also taken into consideration, the presence of multiple calcium deposits in the mitral annulus, aortic valve or aortic root appears to be a marker of CAD in men 55 years old and women.
(J Am Coll Cardiol. 2001;38:1988-1993).
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