James H. O'Keefe

Vitamin D Deficiency : An Important, Common, and Easily Treatable Cardiovascular Risk Factor?

Vitamin D deficiency is a highly prevalent condition, present in approximately 30% to 50% of the general population. A growing body of data suggests that low 25-hydroxyvitamin D levels may adversely affect cardiovascular health. Vitamin D deficiency activates the renin-angiotensin-aldosterone system and can predispose to hypertension and left ventricular hypertrophy. Additionally, vitamin D deficiency causes an increase in parathyroid hormone, which increases insulin resistance and is associated with diabetes, hypertension, inflammation, and increased cardiovascular risk. Epidemiologic studies have associated low 25-hydroxyvitamin D levels with coronary risk factors and adverse cardiovascular outcomes. Vitamin D supplementation is simple, safe, and inexpensive. Large randomized controlled trials are needed to firmly establish the relevance of vitamin D status to cardiovascular health. In the meanwhile, monitoring serum 25-hydroxyvitamin D levels and correction of vitamin D deficiency is indicated for optimization of musculoskeletal and general health.

State-of-the-Art PaperVitamin D Deficiency: An Important, Common, and Easily Treatable Cardiovascular Risk Factor?

Vitamin D deficiency is a highly prevalent condition, present in approximately 30% to 50% of the general population. A growing body of data suggests that low 25-hydroxyvitamin D levels may adversely affect cardiovascular health. Vitamin D deficiency activates the renin-angiotensin-aldosterone system and can predispose to hypertension and left ventricular hypertrophy. Additionally, vitamin D deficiency causes an increase in parathyroid hormone, which increases insulin resistance and is associated with diabetes, hypertension, inflammation, and increased cardiovascular risk. Epidemiologic studies have associated low 25-hydroxyvitamin D levels with coronary risk factors and adverse cardiovascular outcomes. Vitamin D supplementation is simple, safe, and inexpensive. Large randomized controlled trials are needed to firmly establish the relevance of vitamin D status to cardiovascular health. In the meanwhile, monitoring serum 25-hydroxyvitamin D levels and correction of vitamin D deficiency is indicated for optimization of musculoskeletal and general health.

Autonomic Tone as a Cardiovascular Risk Factor: The Dangers of Chronic Fight or Flight

Chronic imbalance of the autonomic nervous system is a prevalent and potent risk factor for adverse cardiovascular events, including mortality. Although not widely recognized by clinicians, this risk factor is easily assessed by measures such as resting and peak exercise heart rate, heart rate recovery after exercise, and heart rate variability. Any factor that leads to inappropriate activation of the sympathetic nervous system can be expected to have an adverse effect on these measures and thus on patient outcomes, while any factor that augments vagal tone tends to improve outcomes. Insulin resistance, sympathomimetic medications, and negative psychosocial factors all have the potential to affect autonomic function adversely and thus cardiovascular prognosis. Congestive heart failure and hypertension also provide important lessons about the adverse effects of sympathetic predominance, as well as illustrate the benefits of beta-blockers and angiotensin-converting enzyme inhibitors, 2 classes of drugs that reduce adrenergic tone. Other interventions, such as exercise, improve cardiovascular outcomes partially by increasing vagal activity and attenuating sympathetic hyperactivity.

Predictors of in-hospital and 6-month outcome after acute myocardial infarction in the reperfusion era: The primary angioplasty in myocardial infarction (PAMI) trial

OBJECTIVES This study examined the predictors of in-hospital and 6-month outcome after different reperfusion strategies in acute myocardial infarction. BACKGROUND Thrombolytic therapy and primary angioplasty are both widely applied as reperfusion modalities in patients with myocardial infarction. Although it is accepted that restoration of early patency of the infarct-related artery can reduce mortality and salvage myocardium, the optimal reperfusion strategy remains controversial, and the predictors of outcome in the reperfusion era have been incompletely characterized. METHODS At 12 centers, 395 patients presenting within 12 h of onset of acute transmural myocardial infarction were prospectively randomized to receive tissue-type plasminogen activator (t-PA) or undergo primary angioplasty without antecedent thrombolysis. Sixteen clinical variables were examined with univariate and multiple logistic regression analysis to identify the predictors of clinical outcome. RESULTS By univariate analysis, in-hospital mortality was increased in the elderly, women, patients with diabetes and in patients treated with t-PA as opposed to angioplasty. Only advanced age and treatment by t-PA versus angioplasty independently correlated with increased in-hospital mortality (6.5% vs. 2.6%, respectively, p = 0.039 by multiple logistic regression analysis). Similarly, the only variables independently related to in-hospital death or nonfatal reinfarction were advanced age and treatment by t-PA versus angioplasty (12.0% vs. 5.1%, p = 0.02). The reduction in in-hospital death or reinfarction with angioplasty versus t-PA was particularly marked in patients > or = 65 years of age (8.6% vs. 20.0%, p = 0.048). Furthermore, primary management with angioplasty versus t-PA was the most powerful multivariate correlate of freedom from recurrent ischemic events (10.3% vs. 28.0%, p = 0.0001). The independent beneficial effect of angioplasty on freedom from death or reinfarction was maintained at 6-month follow-up (8.2% vs. 17.0%, p = 0.02). CONCLUSIONS In the reperfusion era, the two most powerful determinants of freedom from death, reinfarction and recurrent ischemia after myocardial infarction are young age and treatment by primary angioplasty.

Cardiovascular disease resulting from a diet and lifestyle at odds with our Paleolithic genome: how to become a 21st-century hunter-gatherer.

Our genetic make-up, shaped through millions of years of evolution, determines our nutritional and activity needs. Although the human genome has remained primarily unchanged since the agricultural revolution 10,000 years ago, our diet and lifestyle have become progressively more divergent from those of our ancient ancestors. Accumulating evidence suggests that this mismatch between our modern diet and lifestyle and our Paleolithic genome is playing a substantial role in the ongoing epidemics of obesity, hypertension, diabetes, and atherosclerotic cardiovascular disease. Until 500 generations ago, all humans consumed only wild and unprocessed food foraged and hunted from their environment. These circumstances provided a diet high in lean protein, polyunsaturated fats (especially omega-3 [omega-3] fatty acids), monounsaturated fats, fiber, vitamins, minerals, antioxidants, and other beneficial phytochemicals. Historical and anthropological studies show hunter-gatherers generally to be healthy, fit, and largely free of the degenerative cardiovascular diseases common in modern societies. This review outlines the essence of our hunter-gatherer genetic legacy and suggests practical steps to re-align our modern milieu with our ancient genome in an effort to improve cardiovascular health.

Potential adverse cardiovascular effects from excessive endurance exercise.

A routine of regular exercise is highly effective for prevention and treatment of many common chronic diseases and improves cardiovascular (CV) health and longevity. However, long-term excessive endurance exercise may induce pathologic structural remodeling of the heart and large arteries. Emerging data suggest that chronic training for and competing in extreme endurance events such as marathons, ultramarathons, ironman distance triathlons, and very long distance bicycle races, can cause transient acute volume overload of the atria and right ventricle, with transient reductions in right ventricular ejection fraction and elevations of cardiac biomarkers, all of which return to normal within 1 week. Over months to years of repetitive injury, this process, in some individuals, may lead to patchy myocardial fibrosis, particularly in the atria, interventricular septum, and right ventricle, creating a substrate for atrial and ventricular arrhythmias. Additionally, long-term excessive sustained exercise may be associated with coronary artery calcification, diastolic dysfunction, and large-artery wall stiffening. However, this concept is still hypothetical and there is some inconsistency in the reported findings. Furthermore, lifelong vigorous exercisers generally have low mortality rates and excellent functional capacity. Notwithstanding, the hypothesis that long-term excessive endurance exercise may induce adverse CV remodeling warrants further investigation to identify at-risk individuals and formulate physical fitness regimens for conferring optimal CV health and longevity.

Omega-3 Fatty Acids for Cardioprotection

The most compelling evidence for the cardiovascular benefit provided by omega-3 fatty acids comes from 3 large controlled trials of 32,000 participants randomized to receive omega-3 fatty acid supplements containing docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) or to act as controls. These trials showed reductions in cardiovascular events of 19% to 45%. These findings suggest that intake of omega-3 fatty acids, whether from dietary sources or fish oil supplements, should be increased, especially in those with or at risk for coronary artery disease. Patients should consume both DHA and EPA. The target DHA and EPA consumption levels are about 1 g/d for those with known coronary artery disease and at least 500 mg/d for those without disease. Patients with hypertriglyceridemia benefit from treatment with 3 to 4 g/d of DHA and EPA, a dosage that lowers triglyceride levels by 20% to 50%. Although 2 meals of oily fish per week can provide 400 to 500 mg/d of DHA and EPA, secondary prevention patients and those with hypertriglyceridemia must use fish oil supplements if they are to reach 1 g/d and 3 to 4 g/d of DHA and EPA, respectively. Combination therapy with omega-3 fatty acids and a statin is a safe and effective way to improve lipid levels and cardiovascular prognosis beyond the benefits provided by statin therapy alone. Blood DHA and EPA levels could one day be used to identify patients with deficient levels and to individualize therapeutic recommendations.

Effects of Habitual Coffee Consumption on Cardiometabolic Disease, Cardiovascular Health, and All-Cause Mortality

Coffee, after water, is the most widely consumed beverage in the United States, and is the principal source of caffeine intake among adults. The biological effects of coffee may be substantial and are not limited to the actions of caffeine. Coffee is a complex beverage containing hundreds of biologically active compounds, and the health effects of chronic coffee intake are wide ranging. From a cardiovascular (CV) standpoint, coffee consumption may reduce the risk of type 2 diabetes mellitus and hypertension, as well as other conditions associated with CV risk such as obesity and depression; but it may adversely affect lipid profiles depending on how the beverage is prepared. Regardless, a growing body of data suggests that habitual coffee consumption is neutral to beneficial regarding the risks of a variety of adverse CV outcomes including coronary heart disease, congestive heart failure, arrhythmias, and stroke. Moreover, large epidemiological studies suggest that regular coffee drinkers have reduced risks of mortality, both CV and all-cause. The potential benefits also include protection against neurodegenerative diseases, improved asthma control, and lower risk of select gastrointestinal diseases. A daily intake of ∼2 to 3 cups of coffee appears to be safe and is associated with neutral to beneficial effects for most of the studied health outcomes. However, most of the data on coffees health effects are based on observational data, with very few randomized, controlled studies, and association does not prove causation. Additionally, the possible advantages of regular coffee consumption have to be weighed against potential risks (which are mostly related to its high caffeine content) including anxiety, insomnia, tremulousness, and palpitations, as well as bone loss and possibly increased risk of fractures.

Meta-analysis of effect of dipeptidyl peptidase-4 inhibitors on cardiovascular risk in type 2 diabetes mellitus

Patients with type 2 diabetes mellitus (DM) have a very high risk for major adverse cardiovascular (CV) events. Previous studies have shown that traditional oral diabetic medications, despite lowering blood glucose levels, generally do not improve CV outcomes. The safety of some oral hypoglycemic medications has been questioned. We aimed to evaluate the CV safety of dipeptidyl peptidase-4 (DPP4) inhibitors, a novel class of oral diabetic medications, by performing a meta-analysis of DPP4 inhibitors for type 2 DM. A search of electronic databases of published and unpublished literature (until September 30, 2011) was performed to identify randomized controlled trials of ≥24 weeks that compared DPP4 inhibitors to other oral diabetic medications. A meta-analysis was performed using fixed and random effects to determine risk ratio (RR) for adverse CV events with DPP4 inhibitor monotherapy compared to other oral diabetic medications or to placebo. Eighteen randomized met our inclusion criteria, comprising 4,998 patients who were randomized to DPP4 inhibitors and 3,546 to a comparator, with a median duration of therapy of 46.4 weeks. In pooled analysis, the RR of any adverse CV event with a DPP4 inhibitor was 0.48 (0.31 to 0.75, p = 0.001), and the RR for nonfatal myocardial infarction or acute coronary syndrome was 0.40 (0.18 to 0.88, p = 0.02). In conclusion, this meta-analysis provides evidence that DPP4 inhibitors are safe from a CV standpoint and may possibly decrease risk of adverse CV events.

Omega-3 fatty acids: cardiovascular benefits, sources and sustainability

The evidence for the cardioprotective nature of omega-3 fatty acids is abundant, and currently available data indicate that patients with known coronary heart disease should consume at least 1 g daily of long-chain omega-3 fatty acids from either oily fish or fish-oil supplements, and that individuals without disease should consume at least 250–500 mg daily. However, this area of research poses two questions. Firstly, which is the best source of omega-3 fatty acids—fish or fish-oil supplements? Secondly, are recommendations for omega-3 supplementation warranted in view of the rapid depletion of world fish stocks? The argument that eating fish is better than taking fish-oil supplements stems from the fact that several important nutrients, such as vitamin D, selenium, and antioxidants, are missing from the supplements. However, three major prevention trials have clearly indicated that omega-3 fatty acid capsules confer cardiovascular benefits and, therefore, that both are cardioprotective. Sustainable sources of omega-3 fatty acids will need to be identified if long-term cardiovascular risk reduction is to be achieved at the population level.