Cardiovascular causes

Reduction in risk of Ml, stroke, and death from cardiovascular causes - In patients 55 years of age or older at high risk of developing a major cardiovascular event because of a history of coronary artery disease, stroke, peripheral vascular disease, or diabetes that is accompanied by at least 1 other cardiovascular risk factor (eg, hypertension, elevated total cholesterol levels, low FIDL levels, cigarette smoking, documented microalbuminuria). 

Reduction in risk of Ml, stroke, and death from cardiovascular causes -... 

Death from cancer causes/death from cardiovascular causes/death from respiratory causes/death from other causes/survival... 

A = death from cancer causes B = death from cardiovascular causes C = death from other causes D = survival... 

Nissen SE et al Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med 2007 356 2457. [PMID 17517853]... 

The CHARISMA trial (51) enrolled 15,603 patients with either cardiovascular disease or multiple risk factors followed for a median of 28 months. Overall, the dual antiplatelet regimen (aspirin + clopidogrel) was not significantly more effective than aspirin alone in reducing the rate of death, Ml or stroke from cardiovascular causes. 

In the Heart Outcomes Prevention Evaluation 2 (HOPE-2) study, 5522 patients aged 55 or older with vascular disease or diabetes were randomized to treatment with either placebo or a combination 2, 5 mg of folic acid, 50 mg vitamin B6, and I mg vitamin B 2, for an average of five years. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, and stroke. Mean plasma homocysteine levels decreased by 2.4 jimol/L in the treatment group and increased by 0.8 jimol/L in the placebo group. The primary outcome occurred in 18.8% of patients assigned to active therapy and in 19.8% of those assigned to placebo (relative risk = 0.95 95% Cl = 0.84-1.07 P = 0.41) (68). 

EPHESUS (38) AMI within 3-14 days LVEF < 40% diabetes, signs of HF 6642 Eplerenone, 50-mg daily, vs. placebo Significant reduction of all causes of mortality absolute risk reduction 2.3% reduction of rates of deaths and of hospitalization for cardiovascular causes... 

Patients with PAD have increased mortality risk from cardiovascular causes (4,5), which is significantly increased in the subgroup of patients with high serum homocysteine concentration (33,34). Association of a low ABI and high homocysteine level could be useful for identifying patients at excess risk for cardiovascular death (34). In spite of the efficacy in lowering homocysteine level with a folic acid supplement there is no evidence that reducing homocysteine concentration is beneficial in patients with CHD and PAD (26,35),... 

In the CURE study, 12,562 patients with acute coronary syndromes without ST-segment elevation have received ASA and clopidogrel 300 mg bolus, followed by 75 mg daily, versus ASA and placebo (50). The clopidogrel group had early reduction [within 24 hours of treatment—9.3% vs. I 1.4%, RR reduction 20% (p < 0.001) in the primary endpoint death from cardiovascular cause, nonfatal Ml, or stroke], which was sustained at one year, and was observed in all patients with acute coronary syndromes regardless of their level of risk. CURE patients who underwent PCI and were randomized to clopidogrel had a 31% RR reduction in death and Ml compared with placebo-treated PCI patients (51). 

These agents are derivatives of fibric acid and both have the same mechanism of action. However, gemfibrozil [gem FYE bro zil] has largely replaced clofibrate [kloe FYE brate] clinically because of the higher incidence of mortality with the latter agent. The deaths were not associated with cardiovascular causes, but rather with malignancy or complications due to postcholecystectomy and pancreatitis. 

Effect of pravastatin therapy on deaths from all cardiovascular causes. 

Cocaine use may account for up to 25% of acute myocardial infarctions among patients aged 18-45 years. The safety of a 12-hour observation period in a chest pain unit followed by discharge in individuals with cocaine-associated chest discomfort who are at low risk of cardiovascular events has been evaluated in 302 consecutive patients aged 18 years or older (66% men, 70% black, 84% tobacco users) who developed chest pain within 1 week of cocaine use or who tested positive for cocaine (59). Cocaine use was self-reported by 247 of the 302 subjects and rest had urine positive for cocaine 203 had used crack cocaine, 51 reported snorting, and 10 had used it intravenously. Of the 247 who reported cocaine use, 237 (96%) said they had used it in the week before presentation and 169 (68%) within 24 hours before presentation. Follow-up information was obtained for 300 subjects. There were no deaths from cardiovascular causes. Four patients had a non-fatal myocardial infarction during the 30-day period all four had continued to use cocaine. Of the 42 who were directly admitted to hospital, 20 had acute coronary syndrome. The authors suggested that in... 

OPTIME-CHF (5) was a randomized, placebo-controlled study in which 951 patients (mean age 65 years 92% with baseUne NYHA class III or IV mean left ventricular ejection fraction 23%) with acute exacerbations of chronic heart failure in 78 community and tertiary care hospitals in the USA were randomly assigned to a 48-hour infusion of either milrinone (0.5 micrograms/kg/minute initially for 24 hours) or saline (6). The median number of days in hospital for cardiovascular causes within 60 days after randomization did not differ significantly between patients given milrinone (6 days) or placebo (7 days). Sustained hypotension requiring intervention (11 versus 3.2%) and new atrial dysrhythmias (4.6 versus 1.5%) were more common in the patients who received milrinone. There was no difference in hospital mortality (3.8 versus 2.3%), 60-day mortality (10 versus 8.9%), or the composite incidence of death or readmission (35 versus 35%). The authors concluded that these results do not support the routine use of intravenous milrinone as an adjunct to standard therapy in patients with an exacerbation of chronic heart failure. 

Particulate emissions are by-products of fuel combustion, industrial processes, and motor vehicles and are believed to have a significant potential for causing adverse health effects. Carbonaceous material present in atmospheric aerosols is a combination of elemental carbon and organic and inorganic compounds. Particulate matter may also consist of fly ash, minerals, or road dust and contain traces of a number of heavy metals. Population-based studies have consistently found that the association between adverse respiratory effects and particulate concentrations occurs in a number of regions throughout the United States. This association is strongest for PM]o and PM2.5 indices (particulate matter less than 10 and 2.5 pm in diameter, respectively). The observed adverse effects include increases in total mortality, mortality due to respiratory and cardiovascular causes, chronic bronchitis, and hospital visits and admissions for asthma. Elderly or unhealthy individuals and infants appear to comprise subpopulations that are most sensitive to the adverse health effects of PM. 

Among the non-ischaemic cardiovascular causes of thoracic pain that should be ruled out, some present a benign prognosis as pericarditis, while others, in turn, point to a much serious prognosis, such as an acute aortic syndrome (dissecting aneurysm or other aortic pathologies) and a pulmonary embolism. On the whole, these account for 5-10% of all cases of thoracic pain. 

Phosphodiesterase 5 (PDE5) is found in blood vessels supplying the corpora cavernosa. Sildenafil inhibits PDE 5 - T cGMP -> vasodilation - T blood flow ->T erectile response. If used concomitantly with nitrates or other potent vasodilators, the excessive fall in blood pressure may lead to death from cardiovascular causes, including myocardial infarct. 

Despite its proven benefit in the control of blood glucose, PPARy agonists have been associated with an increased incidence of myocardial infarction and death from cardiovascular causes [71]. Numerous companies are therefore working actively on specific PPARa modulators, and a number of discovery and preclinical programs have been initiated with the aim of improving potency and selectivity compared to the fibrates. PPARa-selective compounds that are currently under development are shown in Figure 13.9. With the exception of K-lll (for a recent review, see Ref. [72]), which is developed for the treatment of type 2 diabetes mellitus, the development of all known PPARa activators is focused on lipid metabolism. 

Combination therapy with niacin and a statin has also been shown to produce clinical and angiographic benefits. Brown et al. (56) evaluated the effects of simvastatin in combination with niacin on patients with documented coronary disease in the HATS trial and demonstrated a significant reduction in nonfatal MI or death from cardiovascular causes compared to placebo, albeit with a relatively small number of patients. In the treatment arm, HDL cholesterol increased by 26% over the three years of treatment and was also associated with a slight regression (0.4%) in coronary mean percent stenosis in the proximal arteries by invasive arteriography the placebo arm experienced a 3.9% increase in stenoses. 

The prognostic utility of measuring high-sensitivity C-reactive protein (hsCRP) in patients with established CAD was demonstrated by Ridker et al. (68) in a subsequent analysis of the PROVE IT-TIMI-22 trial. In this study of survivors of acute coronary syndromes, patients who achieved an LDL cholesterol level of 70 mg/dL or less had a reduced risk of nonfatal MI or death from cardiovascular causes. In addition, those patients who achieved an hsCRP level of <2 mg/L also experienced a risk reduction in the primary endpoint of the same magnitude. Interestingly, the most benefit was derived when both an LDL of <70 mg/dL and a hsCRP level of <2 mg/L was achieved, regardless of the statin given. 

The HOPE trial (83) evaluated the use of ramipril compared to placebo in 9,297 high-risk patients, approximately 80% of whom had a history of CAD, and 38% of whom had diabetes. There was a clear benefit to treatment over a mean of five years, including an absolute risk reduction of 2% in death from cardiovascular causes (6.1% versus 8.1%, RR 0.74, P <0.001) and a 2.4% absolute risk reduction in nonfatal MI (9.9% versus 12.3%, RR 0.80, P <0.001). 

In the PEACE trial (86), the use of trandolapril compared to placebo for 4.8 years in patients with stable CAD and a left ventricular EF of >40% did not show a significant benefit in the primary of death from cardiovascular causes, MI, or coronary revascularization. The investigators note that these patients were at lower risk than previous trials, with a preserved EF (mean 58 9%) and higher rates of treatment with... 

Zethelius B, Berglund L, Sundstrom J, et al. Use of multiple biomarkers to improve the prediction of death from cardiovascular causes. N Engl J Med 2008 358(20) 2107-16. 

Increased mortality from cardiovascular causes was noted in a 1975-1985 epidemiological study of 251 workers exposed to carbon disulfide compared to 124 nonexposed workers in two viscose rayon factories in Czechoslovakia (Balcarova and Halik 1991). The workers (spinners) were exposed to "high" levels of carbon disulfide with estimated concentrations ranging from less than 9.6 to 48 ppm. An increased incidence of myocardial infarction was also noted in the highly exposed group compared to controls. However, this study should be interpreted with caution since scanty data were provided regarding methods employed. 

In adults, GH deficiency is associated with a defined endocrinopathy that includes increased mortality from cardiovascular causes, probably secondary to deleterious changes in fat distribution, increases in circulating lipids, and increased inflammation decreased muscle mass and exercise capacity decreased bone density and impaired psychosocial function. In GH-deficient adults, the consensus is that the most severely affected GH-defident adults may benefit the most from GH replacement therapy. The FDA also has approved GH therapy for AIDS-associated wasting and for malabsorption associated with the short bowel syndrome. In this latter setting, GH is administered once daily for 4 weeks. 

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