James H. O’Keefe

Dietary Strategies for Improving Post-Prandial Glucose, Lipids, Inflammation, and Cardiovascular Health

The highly processed, calorie-dense, nutrient-depleted diet favored in the current American culture frequently leads to exaggerated supraphysiological post-prandial spikes in blood glucose and lipids. This state, called post-prandial dysmetabolism, induces immediate oxidant stress, which increases in direct proportion to the increases in glucose and triglycerides after a meal. The transient increase in free radicals acutely triggers atherogenic changes including inflammation, endothelial dysfunction, hypercoagulability, and sympathetic hyperactivity. Post-prandial dysmetabolism is an independent predictor of future cardiovascular events even in nondiabetic individuals. Improvements in diet exert profound and immediate favorable changes in the post-prandial dysmetabolism. Specifically, a diet high in minimally processed, high-fiber, plant-based foods such as vegetables and fruits, whole grains, legumes, and nuts will markedly blunt the post-meal increase in glucose, triglycerides, and inflammation. Additionally, lean protein, vinegar, fish oil, tea, cinnamon, calorie restriction, weight loss, exercise, and low-dose to moderate-dose alcohol each positively impact post-prandial dysmetabolism. Experimental and epidemiological studies indicate that eating patterns, such as the traditional Mediterranean or Okinawan diets, that incorporate these types of foods and beverages reduce inflammation and cardiovascular risk. This anti-inflammatory diet should be considered for the primary and secondary prevention of coronary artery disease and diabetes.

Exercise and the Cardiovascular System: Clinical Science and Cardiovascular Outcomes

Substantial evidence has established the value of high levels of physical activity, exercise training (ET), and overall cardiorespiratory fitness in the prevention and treatment of cardiovascular diseases. This article reviews some basics of exercise physiology and the acute and chronic responses of ET, as well as the effect of physical activity and cardiorespiratory fitness on cardiovascular diseases. This review also surveys data from epidemiological and ET studies in the primary and secondary prevention of cardiovascular diseases, particularly coronary heart disease and heart failure. These data strongly support the routine prescription of ET to all patients and referrals for patients with cardiovascular diseases, especially coronary heart disease and heart failure, to specific cardiac rehabilitation and ET programs.

Dose of Jogging and Long-Term Mortality : The Copenhagen City Heart Study

BACKGROUND People who are physically active have at least a 30% lower risk of death during follow-up compared with those who are inactive. However, the ideal dose of exercise for improving longevity is uncertain. OBJECTIVES The aim of this study was to investigate the association between jogging and long-term, all-cause mortality by focusing specifically on the effects of pace, quantity, and frequency of jogging. METHODS As part of the Copenhagen City Heart Study, 1,098 healthy joggers and 3,950 healthy nonjoggers have been prospectively followed up since 2001. Cox proportional hazards regression analysis was performed with age as the underlying time scale and delayed entry. RESULTS Compared with sedentary nonjoggers, 1 to 2.4 h of jogging per week was associated with the lowest mortality (multivariable hazard ratio [HR]: 0.29; 95% confidence interval [CI]: 0.11 to 0.80). The optimal frequency of jogging was 2 to 3 times per week (HR: 0.32; 95% CI: 0.15 to 0.69) or ≤1 time per week (HR: 0.29; 95% CI: 0.12 to 0.72). The optimal pace was slow (HR: 0.51; 95% CI: 0.24 to 1.10) or average (HR: 0.38; 95% CI: 0.22 to 0.66). The joggers were divided into light, moderate, and strenuous joggers. The lowest HR for mortality was found in light joggers (HR: 0.22; 95% CI: 0.10 to 0.47), followed by moderate joggers (HR: 0.66; 95% CI: 0.32 to 1.38) and strenuous joggers (HR: 1.97; 95% CI: 0.48 to 8.14). CONCLUSIONS The findings suggest a U-shaped association between all-cause mortality and dose of jogging as calibrated by pace, quantity, and frequency of jogging. Light and moderate joggers have lower mortality than sedentary nonjoggers, whereas strenuous joggers have a mortality rate not statistically different from that of the sedentary group.

Long-term outcome after primary angioplasty: report from the Primary Angioplasty in Myocardial Infarction (PAMI-I) trial

OBJECTIVES This study sought to compare the two-year outcome after primary percutaneous coronary angioplasty or thrombolytic therapy for acute myocardial infarction. BACKGROUND Primary angioplasty, that is, angioplasty without antecedent thrombolytic therapy, has been shown to be an effective reperfusion modality for patients suffering an acute myocardial infarction. This report reviews the two-year clinical outcome of patients randomized in the Primary Angioplasty in Myocardial Infarction trial. METHODS At 12 clinical centers, 395 patients who presented within 12 h of the onset of myocardial infarction were randomized to undergo primary angioplasty (195 patients) or to receive tissue-type plasminogen activator (t-PA) (200 patients) followed by conservative care. Patients were followed by physician visits, phone call, letter and review of hospital records for any hospital admission at one month, six months, one year and two years. RESULTS At two years, patients undergoing primary angioplasty had less recurrent ischemia (36.4% vs. 48% for t-PA, p = 0.026), lower reintervention rates (27.2% vs. 46.5% for t-PA, p < 0.0001) and reduced hospital readmission rates (58.5% vs. 69.0% for t-PA, p = 0.035). The combined end point of death or reinfarction was 14.9% for angioplasty versus 23% for t-PA, p = 0.034. Multivariate analysis found angioplasty to be independently predictive of a reduction in death, reinfarction or target vessel revascularization (p = 0.0001). CONCLUSIONS The initial benefit of primary angioplasty performed by experienced operators is maintained over a two-year follow-up period with improved infarct-free survival and reduced rate of reintervention.

Estrogen Replacement Therapy After Coronary Angioplasty in Women

OBJECTIVES The purpose of this study was to assess the effects of estrogen replacement therapy on long-term outcome, including restenosis, myocardial infarction, stroke and death after a first percutaneous transluminal coronary angioplasty (PTCA) procedure, in postmenopausal women. BACKGROUND Observational and epidemiologic studies, basic laboratory research and clinical trials consistently suggest that estrogen replacement therapy is associated with beneficial cardiovascular effects in women. These cardioprotective actions may be particularly relevant to women with coronary artery disease, such as those who have undergone PTCA. METHODS This was a retrospective study that included 337 women who underwent elective PTCA between 1982 and 1994. The treatment group consisted of 137 consecutive women receiving long-term estrogen therapy at the time of elective PTCA and during follow-up. The control group comprised 200 women who were computer-matched with the estrogen group. The mean follow-up period was 65 +/- 35 months. RESULTS Actuarial survival was superior in the estrogen group; the 7-year survival rate was 93% for the estrogen group versus 75% for the control group (p = 0.001). The cardiovascular event rate (death, nonfatal myocardial infarction or nonfatal stroke) was significantly lower in the estrogen group at 7 years (12% vs. 35% in the control group, p = 0.001). The need for subsequent revascularization during follow-up was similar in the two groups. Multivariable analysis identified diabetes, estrogen therapy (adjusted risk ratio 0.38, 95% confidence interval 0.19 to 0.79) and left ventricular ejection fraction < 40% as independent correlates of cardiovascular death or myocardial infarction during follow-up. CONCLUSIONS Estrogen replacement therapy was associated with an improved long-term outcome after PTCA in postmenopausal women.

Alcohol and Cardiovascular Health: The Dose Makes the Poison…or the Remedy

Habitual light to moderate alcohol intake (up to 1 drink per day for women and 1 or 2 drinks per day for men) is associated with decreased risks for total mortality, coronary artery disease, diabetes mellitus, congestive heart failure, and stroke. However, higher levels of alcohol consumption are associated with increased cardiovascular risk. Indeed, behind only smoking and obesity, excessive alcohol consumption is the third leading cause of premature death in the United States. Heavy alcohol use (1) is one of the most common causes of reversible hypertension, (2) accounts for about one-third of all cases of nonischemic dilated cardiomyopathy, (3) is a frequent cause of atrial fibrillation, and (4) markedly increases risks of stroke-both ischemic and hemorrhagic. The risk-to-benefit ratio of drinking appears higher in younger individuals, who also have higher rates of excessive or binge drinking and more frequently have adverse consequences of acute intoxication (for example, accidents, violence, and social strife). In fact, among males aged 15 to 59 years, alcohol abuse is the leading risk factor for premature death. Of the various drinking patterns, daily low- to moderate-dose alcohol intake, ideally red wine before or during the evening meal, is associated with the strongest reduction in adverse cardiovascular outcomes. Health care professionals should not recommend alcohol to nondrinkers because of the paucity of randomized outcome data and the potential for problem drinking even among individuals at apparently low risk. The findings in this review were based on a literature search of PubMed for the 15-year period 1997 through 2012 using the search terms alcohol, ethanol, cardiovascular disease, coronary artery disease, heart failure, hypertension, stroke, and mortality. Studies were considered if they were deemed to be of high quality, objective, and methodologically sound.

Should an angiotensin-converting enzyme inhibitor be standard therapy for patients with atherosclerotic disease?

Angiotensin-converting enzyme (ACE) inhibitors appear to possess unique cardioprotective benefits, even when used in patients without high blood pressure or left ventricular dysfunction (the traditional indications for ACE inhibitor therapy). The ACE inhibitors improve endothelial function and regress both left ventricular hypertrophy and arterial mass better than other antihypertensive agents that lower blood pressure equally as well. These agents promote collateral vessel development and improve prognosis in patients who have had a coronary revascularization procedure (i.e., percutaneous transluminal coronary angioplasty and coronary artery bypass graft surgery). Insulin resistance, present not only in type 2 diabetes but also commonly in patients with hypertension or coronary artery disease, or both, sensitizes the vasculature to the trophic effects of angiotensin II and aldosterone. This may partly explain the improvement in prognosis noted when patients who have atherosclerosis or diabetes are treated with an ACE inhibitor. Therapy with ACE inhibitors has also been shown, in two large, randomized trials, to reduce the incidence of new-onset type 2 diabetes through largely unknown mechanisms. The ACE inhibitors are safe, well tolerated and affordable medications. The data suggest that most people with atherosclerosis should be considered candidates for ACE inhibitor therapy, unless they are intolerant to the medication, or have systolic blood pressures consistently <100 mm Hg. Patients who show evidence of insulin resistance (with or without overt type 2 diabetes) should also be considered as candidates for prophylactic ACE inhibitor therapy. Although angiotensin receptor blockers should not be considered equivalent to ACE inhibitors for this indication, they may be a reasonable alternative for patients intolerant of ACE inhibitors.

Coronary calcium screening in asymptomatic patients as a guide to risk factor modification and stress myocardial perfusion imaging

Background. Previous studies have demonstrated a correlation between the extent of coronary artery calcification (CAC) and atherosclerotic plaque. As a result, CAC screening could be useful in predicting cardiovascular risk in individuals in whom atherosclerosis is developing. One possible method of detecting and quantifying CAC is by x-ray computed tomography, which potentially allows one to stratify patients into groups requiring risk factor modification or follow-up testing such as myocardial perfusion single photon emission computed tomography (SPECT).Methods and Results. This study was designed to evaluate the clinical utility of multidetector computed tomography (MDCT) in a cardiology practice setting. A retrospective analysis was performed on data from 794 asymptomatic patients who underwent CAC screening over an 8-month period. On the basis of the CAC score and physician consultation, 102 patients underwent subsequent myocardial perfusion SPECT imaging. A substudy was also conducted in 306 patients to measure the interscan variability of MDCT across different CAC score ranges. CAC was detected in 422 of 794 patients. Of these, the CAC was moderate (Agatston score = 101–400) in 14% and severe (>400) in 9%. Patients with 3 or more cardiac risk factors were most likely to exhibit moderate to severe CAC. In myocardial perfusion SPECT testing, no patient with an Agatston score lower than 100 had an abnormal study. In contrast, 41% of patients with severe CAC had an abnormal SPECT study. In the reproducibility substudy the minimal CAC group had the largest variability (86.0%) whereas the severe CAC group had the lowest variability (9.5%).Conclusion. CAC screening with MDCT is justified for asymptomatic patients with 3 or more cardiac risk factors. However, risk factor assessment is poor at predicting which individuals will have CAC if fewer risk factors are present. In terms of the interscan variability, MDCT is capable of following changes in CAC for patients with Agatston scores greater than 100. Finally, this study demonstrated that an Agatston score of 400 is a logical threshold to initiate follow-up myocardial perfusion SPECT testing. (J Nucl Cardiol 2003;10:590-8.)

Usefulness of Technetium-99m Sestamibi Infarct Size in Predicting Posthospital Mortality Following Acute Myocardial Infarction

In this multicenter study, 249 patients who underwent tomographic technetium-99m sestamibi infarct size measurement at hospital discharge were followed up for a median duration of 7 months. Infarct size was significantly associated with mortality (chi-square = 5.8, p = 0.02) and could stratify patients into lower and higher risk subsets: 1-year mortality 2% for infarct size < 14% versus 8% for infarct size > or = 14% of the left ventricle.

C-Reactive Protein and Cardiovascular Diseases—Is it Ready for Primetime?

C-reactive protein (CRP) is a marker of systemic inflammation, and it has been implicated in the pathogenesis of many chronic diseases, including cardiovascular (CV) diseases. With highly sensitive CRP assays, serum CRP can add considerably to standard coronary heart disease risk factors and in the prediction of subsequent major CV risk. We review evidence supporting the assessment of highly sensitive CRP both in patients with established CV diseases and in those without known disease as well as evidence supporting CRP as a target of therapy. We also review various pharmacologic (especially intensive statin therapy) and nonpharmacologic therapies to reduce levels of CRP.