Coffee Consumption and Risk of Cardiovascular Events After Acute MI

Further information: Treatment of Acute ST-Elevation Myocardial Infarction from Cardiovascular Medicine, 3rd Edn*

Using data from the Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico (GISSI)-Prevenzione trial, the authors of this study evaluated and analyzed 11,231 Italian patients from the GISSI trial (9584 males and 1647 females) who had a recent (≤ 3 months) myocardial infarction (MI), with the purpose of the study being to determine if there is an association between coffee consumption and cardiovascular disease [1].

The participants’ coffee consumption was determined through a questionnaire to learn the participants’ use of the Mediterranean Diet, such as the amount of fish, fruit, raw vegetables, olive oils and other oils, wine, and coffee consumed. Regarding coffee consumption, participants were asked if their use were as follows: never/almost never; less than two cups; 2–4 cups; or more than four cups per day. Primary outcome was combined incidence of cardiovascular death, nonfatal MI, or stroke; additional analyses included the cumulative rate of sudden death, nonfatal plus fatal stroke, and nonfatal and fatal MI as independent variables.

After multivariable adjustment for potential confounders in the time-dependent analysis, the relative risk of cardiovascular events across the categories of coffee consumption was 1.02 (95% CI 0.87–1.20) for less than two cups per day. 0.91 (95% CI 0.75–1.09) for 2–4 cups per day, and 0.88 (95% CI 0.64–1.20) for more than four cups per day compared with those who did not drink coffee (P for trend = 0.18.). Of the patients evaluated, there were 670 cardiovascular deaths, 456 nonfatal MIs, and 119 nonfatal strokes, and 70 % of the cardiovascular events occurred in patients with low coffee intake. After having assessed the dietary habits and coffee consumption at baseline, 0.5, 1.5, 2.5 and 3.5 years, no association between moderate coffee intake and cardiovascular events, stroke risk, or sudden death was observed.

[1] Silletta, SG, Marfisi RM, Levantesi G, et al. Coffee consumption and risk of cardiovascular events after acute myocardial infarction. Circulation 2007;116:2944-51

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Drug-Eluting Stents vs. CABG in Multivessel Coronary Disease

Further information: CABG and Percutaneous Coronary Revasculaization from Cardiovascular Medicine, 3rd Edn*

This study [1] is the first large-scale, multicenter comparison of two methods used to revascularization patients with multivessel coronary disease. The two primary databases used for comparison were the Cardiac Surgery Reporting System (CSRS) and the Percutaneous Coronary Intervention Reporting System (PCIRS) of the New York State Department of Health. Patients with multivessel disease who received either coronary artery bypass surgery (CABG) or drug-eluting stents (EDS) between October 1, 2003 and December 1, 2004 were evaluated for adverse outcomes through December 31, 2005.

After adjustments were made for differences in baseline risk factors, the authors of the study compared adverse outcomes which were death, myocardial infarction, or repeat visualization. A total of 7437 patients had CABG and 9963 patients had DES. Of 7437 patients who had CABG, 5202 had three-vessel disease and 2235 had two-vessel disease. Of 9963 patients who had DES, 2481 had three-vessel disease and 7482 had two-vessel disease. In patients having CABG with three-vessel disease, as compared with those who received DES, the adjusted hazard ratio(AHR) for death was 0.80 (95% confidence interval [CI], 0.65–0.97) and the adjusted survival rate (ASR) 94.0% vs. 92.7% (P=0.03); the AHR for death or MI was 0.75% (95% CI, 0.63–0.89) and the adjusted rate of survival free from MI was 92.1% vs. 89.7% (P<0.001). In patients with two-vessel disease who had CABG as compared with those having DES, the ASR was 96.0% vs. 94.6% (P=0.003); the AHR for death or MI was 0.71 (95% CI, 0.59–0.87) and the ARS free from MI was 94.5% vs. 92.5% (P<0.001).

The authors of this comparative study concluded that lower mortality rates are associated with CABG and with DES, and CABG is also associated with lower rates of MI and revascularization. However, there are important factors to be considered before a final determination is made from the results of this study. It is important to consider that this was an observational study and patients with left main disease were not included; thus, it was not possible to eliminate a bias caused by the presence of patients who would not have been eligible to be included in a randomized, controlled trial because they were too sick, had contraindications, or had unmeasured risk factors.

[1] Hannan EL, Wu C, Walford G, et al. Drug-eluting stents vs. coronary artery bypass grafting in multivessel coronary disease. N Engl J Med 2008;358:331-41

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Outcomes in Athletes with Marked ECG Repolarization Abnormalities

Further information: Hypertrophic Cardiomyopathy from Cardiovascular Medicine, 3rd Edn*

In Italy’s Institute of Sports Medicine and Science, all trained athletes selected to participate in a competition are required to undergo preparticipation screening to rule out the presence of cardiovascular disease that could indicate an increased risk to the athlete during training and competition.

From a database of 12,550 trained athletes, the authors of this study [1] sought to evaluate a small subgroup of athletes (n=81) with abnormal 12-lead ECGs suggestive of left ventricular hypertrophy, but without evidence of structural cardiac disease. These repolarized abnormalities, usually thought to result from exercise training, may show diffusely and deeply inverted T waves (≥2mm in at least three leads) that suggest underlying genetic cardiomyopathies that may not manifest themselves for many years, but have adverse outcomes. Comparisons were made with a control group of 229 athletes with normal ECGs from the same database.

Of the 81 athletes who were identified as having abnormal ECGs, 6% (n=5) did have cardiomyopathies, and one of them died at age 24 from undetected arrhythmogenic right ventricular cardiomyopathy. Of the 80 who remained, three developed clinical and phenotypic features of hypertrophic cardiomyopathy after 12±5 years (at age 27, 32, and 50 years) and included one who had an aborted cardiac arrest. After nine years of follow-up, the fifth athlete developed dilated cardiomyopathy. However, none of the 229 control athletes with normal ECGs had a cardiac event or ever had a cardiomyopathy diagnosed 9±3 years after the initial evaluation (P=0.001).

In conclusion, the data showing ECG abnormalities should be considered useful to identify athletes at risk of developing structural heart disease, and they underscore the need for greater diagnostic and clinical observation of such athletes.

[1] Pelliccia A, Di Paolo FM, Quattrini FM, et al. Outcomes in athletes with marked ECG repolarization abnormalities. N Engl J Med 2008;358:152-61.

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Pharmacogenetic Association of the NPPA T2238C Genetic Variant with Cardiovascular disease Outcomes in Patients with Hypertension

Further information: Hypertension from Cardiovascular Medicine, 3rd Edn*

Authors from the University of Texas School of Public Health, the University of Minnesota, and the University of Alabama conducted a study to examine whether patients with hypertension with minor atrial natriuretic precursor A (NPPA) genotypes (NPPA G664A and NPPA T2238C) randomized to the diuretic chlorthalidone had different outcomes for cardiovascular disease (CVD) measures than patients who were randomized to other classes of antihypertensive medication [1]. Previous research has suggested that the NAPPA gene may influence the effectiveness of some antihypertensive drugs.

Study participants were initially involved in a multi-center, randomized , double-blind 2002 landmark investigation based at The University of Texas School of Public Health establishing that relatively inexpensive diuretics were as good as three other classes of medications to treat hypertension. DNA of the participants in the 2002 Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) was captured and used in the present study. Participants were also part of the Genetics of Hypertension Associated Treatment (GenHAT) study, an ancillary study to ALLHAT. Although hypertension affects at least 65 million Americans and contributes to heart failure, stroke, and heart attack, only about two-thirds of the people receiving treatment have controlled hypertension.

By genetically analyzing 38,462 participants with blood pressure readings of 140/90 mmHg, researchers found that slight variants in the gene NPPA appeared to impact the effectiveness of medications for hypertension. Patients were randomly assigned to a diuretic (chlorthalidone; n=13,860), a calcium channel blocker (amlodipine; (n=8174), an angiotensin-converting enzyme (ACE) inhibitor (lisinopril; n=8233), or an alpha-blocker (doxazosin; n=8195). The follow-up period averaged 4.9 years. The primary outcome measure was coronary heart disease (CHD), defined as fatal CHD or nonfatal myocardial infarction (MI). Secondary outcomes were stroke, all-cause mortality, combined cardiovascular disease outcomes, and 6-month systolic and diastolic BP changes. The goal of GenHAT was to understand gene-treatment interactions on CVD outcomes and blood pressure lowering.

Depending on genotype, the event rates per 1000 person-years were 15.3–19.7 for CHD, 9.6–15.4 for stroke, and 27.4–30.7 for all-cause mortality. For the NPPA T2238C variant, lower event rates were found for the C allele carriers than for the TT homozygous individuals when comparing chlorthalidone and amlodipine (CHD: CC=0.86;TC=0.90; TT=1.09; P=0.03 [dominant model]; stroke: CC=1.18; TC=0.82; TT=1.26; P=0.01 [additive and dominant models]); all-cause mortality: CC=0.87; TC=0.98; TT=1.12; P=0.05 [dominant model]). Combined end points were similar. Consistent with these clinical findings, 6-month changes in systolic BP for those with the CC genotypes showed larger reductions with chlorthalidone (-6.5 mmHg) than with amlodipine (-3.8 mmHg), lisinopril (-2.4 mmHg), or doxazosin (-3.8 mmHg). Among those with the TT genotype, systolic BP differences between drugs were less (range, -5.4 to -7.5 mmHg; P value, <0.001–0.003 for interaction); diastolic BP showed similar results.

The authors found no pharmacogenetic associations with the NPPA G664A variant, but instead found that the NPPA T2238C variant was associated with modification of antihypertensive medication effects on CVD and BP. Minor C allele carriers experienced more favorable CVD outcomes when randomized to receive a diuretic, whereas TT allele carriers had more favorable outcomes when randomized to receive a calcium channel blocker.

[1] Lynch AI, Boerwinkle E, Davis BR, et al. Pharmacogenetic association of the NPPA T2238C genetic variant with cardiovascular disease outcomes in patients with hypertension. JAMA 2008:299:296-307

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* To view the online text from the book, please navigate to SpringerLink or use the DVD to access electronic content. SpringerLink is a subscription service. For further information, click here.

Adjustable Gastric Banding and Conventional Therapy for Type 2 Diabetes

Further information: Cardiovascular Complications of Obesity and the Metabolic Syndrome from Cardiovascular Medicine, 3rd Edn*

Researchers from Monash University and the University of Melbourne studied 60 patients with type 2 diabetes to evaluate laparoscopic adjustable gastric banding (LAGB) surgery compared to conventional approaches to weight loss and diabetes control in obese patients with recently diagnosed diabetes [1]. An unblinded, randomized, controlled trial was conducted from December 2002 through December 2006 by researchers in Australia to determine which method resulted in better glycemic control and less need for dependence on diabetes medications.

The primary outcome measures were remission of type 2 diabetes (fasting glucose level <126 mg/dl [7.0 mmol/L] and glycated hemoglobin [HbA1C] value <6.2% while taking no glycemic therapy). Secondary measures included weight, blood pressure (BP), percentage change in HbA1C levels, waist circumference, and levels of fasting lipids. Also assessed were changes in medication use, proportion of participants with metabolic syndrome, and changes in indirect measures of insulin resistance.

Of the 60 enrolled patients, 55 (92%) completed the two-year follow-up. Remission of type 2 diabetes was achieved by 22 (73%) in the surgical group and four (13%) in the conventional therapy group. Relative risk for remission in the surgical group was 5.5 (95% confidence interval [CI], 2.2–14.0). Surgical and conventional therapy groups lost a mean weight (SD) of 20.7% (8.6%) and 1.7% (5.2%) respectively at two years (P<0.001). Remission of type 2 diabetes was related to weight loss (R2=0.46, P<0.001) and lower baseline HbA1C levels (combined R2=0.52, P<0.001). No serious complications occurred in either group. The study found superior glycemic control and diabetes remissions rates with LAGE surgery.

After 2 years, the surgical group had a five times higher remission rate and four times greater reduction in HbA1C levels than the conventional therapy group. In addition, the study also showed higher rates of resolution of the metabolic syndrome. Another important finding was that the degree of weight loss, not the method, appears to be the major factor in glycemic improvement and diabetes remission, indicating that intensive weight-loss therapy may be a more effective first step in the management of diabetes than lifestyle change. Although caution is needed in interpreting the longer-term benefits of surgery and weight-loss, this study provides strong evidence for an early consideration of LAGB surgery to treat obese patients with type 2 diabetes.

[1] Dixon JB, O’Brien PE, Playfair J, et al. Adjustable Gastric Banding and Conventional Therapy for Type 2 Diabetes. JAMA 2008:299:316-23

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