Despite striking extensions of lifespan, leading causes of death in most countries now constitute chronic, degenerative diseases which outpace the capacity of health systems. Cardiovascular disease is the most common cause of death in both developed and undeveloped countries. In America, nearly half of the adult population has at least one chronic disease, and polypharmacy is commonplace. Prevalence of ideal cardiovascular health has not meaningfully improved over the past two decades. The fall in cardiovascular deaths in Western countries, half due to a fall in risk factors and half due to improved treatments, have plateaued, and this reversal is due to the dual epidemics of obesity and diabetes type 2. High burdens of cardiovascular risk factors are also evident globally. Undeveloped nations bear the burdens of both infectious diseases and high childhood death rates. Unacceptable rates of morbidity and mortality arise from insufficient resources to improve sanitation, pure water, and hygiene, ultimately linked to poverty and disparities. Simultaneously, about 80% of cardiovascular deaths now occur in low- and middle-income nations. For these reasons, risk factors for noncommunicable diseases, including poverty, health illiteracy, and lack of adherence, must be targeted with unprecedented vigor worldwide. Key messages In developed and relatively wealthy countries, chronic "degenerative" diseases have attained crisis proportions that threaten to reverse health gains made within the past decades. Although poverty, disparities, and poor sanitation still cause unnecessary death and despair in developing nations, they are now also burdened with increasing cardiovascular mortality. Poor adherence and low levels of health literacy contribute to the high background levels of cardiovascular risk.

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Coronary heart disease (CHD) is the leading cause of death in most countries, with the high prevalence currently driven by dual epidemics of obesity and diabetes. Statin drugs, the most effective, evidence-based agents to prevent and treat this disease, have a central role in management and are advised in all published guidelines. The 2013 American College of Cardiology/American Heart Association (ACC/AHA) cholesterol and assessment guidelines ('new ACC/AHA guidelines') emphasized global cardiovascular (CV) risk reduction as opposed to targeting low-density lipoprotein-cholesterol (LDL-C) levels, stressed the use of statins in two dose intensities, utilized a new risk calculator using pooled cohort equations, and lowered the risk cutoff for initiation of statin therapy. Although there were major strengths of the new ACC/AHA guidelines, substantial controversy followed their release, particulars of which are discussed in this review. They were generally regarded as improvements in an ongoing transition using evidenced-based data for maximum patient benefit. Several guidelines, other than the ACC/AHA guidelines, currently provide practitioners with choices, some depending on practice locations. Cholesterol control with statin drugs is used in all paradigms. However, some patients respond inadequately, approximately 15% are intolerant, and other factors prevent attaining cholesterol goals in as many as 40% of patients. Even after treatment, substantial residual risk for ongoing major events remains. Another readily available modality that can rival statin drugs in effectiveness is vast improvement in diet and lifestyle within the general population; however, despite great effort, existing programs to implement such changes have failed. Hence, despite unrivaled success, there is great need for additional drugs to prevent and treat CHD, whether as monotherapy or in combination with statin drugs. New American guidelines do not discuss or recommend any nonstatin drugs for CHD, and the US FDA has moved away from approving drugs based solely on changes in surrogates in the absence of clinical outcomes trials. Both have significantly altered the realities of developing pharmacotherapies and cardiology practice.

Amidst voluminous literature, inconsistencies and opposing results have confused rather than clarified cardiologists' ability to assess the potential benefits of n-3 polyunsaturated fatty acids (n-3 PUFA). In perspective, there are common themes that emerge from n-3 PUFA studies, even as imperfect as they may be. The approach taken was to identify and unite these themes into a manageable, cohesive, evidence-based, yet useful synthesis. In all reviews and meta-analyses, the selection of component studies and assumptions influences outcomes. This overarching principle must be combined with the totality of the data, particularly when evidence is incompletely understood and gaps in knowledge must be bridged. Both the older literature and the most recent rigorous meta-analyses indicate that n-3 PUFA are highly pleiotropic agents with many documented positive physiological effects. Concordance among preclinical, observational, randomized clinical trials and meta-analyses is impressive. These agents have modest, statistically significant benefits which accrue over time. Given their favorable safety profile, a risk reduction of about 10% justifies their potential use in cardiovascular disease.

Despite remarkable decreases in the mortality of coronary heart disease, there is concern that continued high levels of cardiovascular risk in the population may reverse these gains. By 2015, the prevalence of cardiovascular disease in the United States will be 37.8%. Obesity, hypertension, dyslipidemia, diabetes mellitus (DM), metabolic syndrome, and inflammation are the primary components driving cardiovascular risk. Approximately 70% of adults are overweight or obese, yet diet quality continues to deteriorate and authoritative information is insufficiently promoted. More than half of US adults have lipid abnormalities; 27% of US adults have high values of low-density lipoprotein cholesterol, 23% have low values of high-density lipoprotein cholesterol concentrations, and 30% have high triglyceride levels. Approximately 34% of adults have hypertension; 40% of these adults are unaware of the diagnosis. In patients with hypertension who are treated, 54% remain uncontrolled. The prevalence of hypertension in elderly patients has increased from 35% to 41%. In addition, 30% of adults have prehypertension. The burden of hypertension alone accounts for approximately 1000 deaths per day. Trends in the prevalence of glucose intolerance are similar. The prevalence of DM is approximately 12%, with 27% of cases remaining undiagnosed. Thirty-five percent of US adults aged > 20 years have prediabetes and 7.3% of adults are unaware of the diagnosis. If the present trends continue, 1 in 3 of US adults will have DM by 2050. Participation in exercise has been low and a "straight line" for > 2 decades. Accelerometer data indicate that individuals who attain minimal exercise goals are only a fraction of the often quoted levels of > 35%. Control of risk factors in primary prevention, although improved, remains decidedly incomplete. Lowering the burden of cardiovascular risk factors at the population level has been exceptionally difficult. For reasons outlined, the solution to this problem is multifaceted and extends well beyond the delivery of medical care into the structure of society and the environment.