1.
Prevention of Metabolic Syndrome by Telephone-Delivered Lifestyle Intervention in a Real-World Setting: Sub-Analysis of a Cluster-Randomized Trial.
Sakane, N, Kotani, K, Suganuma, A, Takahashi, K, Sato, J, Suzuki, S, Izumi, K, Kato, M, Noda, M, Nirengi, S, et al
Metabolic syndrome and related disorders. 2019;(7):355-361
Abstract
Background: Evidence of the long-term benefits of telephone-delivered lifestyle interventions is limited. This study investigated the ability of telephone-delivered lifestyle intervention to reduce the incidence of metabolic syndrome (MetS) in subjects diagnosed with impaired fasting glucose (IFG) during health checkups. Methods: Our subjects were participants in the Japan Diabetes Outcome Intervention Trial-1 (J-DOIT1), a prospective, cluster-randomized controlled trial designed to investigate whether goal-focused lifestyle coaching over the telephone can effectively reduce the incidence of type 2 diabetes development in high-risk individuals in a primary health care setting. We extracted 753 and 844 J-DOIT1 participants from the intervention and controls arms, respectively, who had IFG but did not meet the MetS criteria at baseline. The intervention arm received goal-focused lifestyle support delivered by health care providers via telephone over a 1-year period. The endpoint was the development of incident MetS, defined based on the Adult Treatment Panel III criteria modified for Japan. Results: During the median follow-up period of 4.9 years, 8.0% of the intervention arm and 12.0% of the control arm developed MetS. Overall, the hazard ratio (HR) for the development of MetS was 0.75 [95% confidence interval (CI), 0.52-1.09; P = 0.14] in the intervention arm. However, the HR in overweight or obese [body mass index (BMI) ≥23 kg/m2] individuals was significantly reduced to 0.63 (95% CI, 0.41-0.95; P = 0.029), but not in lean (BMI <23 kg/m2) individuals. Conclusion: Telephone-delivered lifestyle intervention effectively reduced the incidence of MetS in overweight and obese subjects in a real-world setting. Clinical trial registration number: UMIN000000662 (registered March 30, 2007; https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000000798).
2.
Molecular sources of residual cardiovascular risk, clinical signals, and innovative solutions: relationship with subclinical disease, undertreatment, and poor adherence: implications of new evidence upon optimizing cardiovascular patient outcomes.
Kones, R
Vascular health and risk management. 2013;:617-70
Abstract
Residual risk, the ongoing appreciable risk of major cardiovascular events (MCVE) in statin-treated patients who have achieved evidence-based lipid goals, remains a concern among cardiologists. Factors that contribute to this continuing risk are atherogenic non-low-density lipoprotein (LDL) particles and atherogenic processes unrelated to LDL cholesterol, including other risk factors, the inherent properties of statin drugs, and patient characteristics, ie, genetics and behaviors. In addition, providers, health care systems, the community, public policies, and the environment play a role. Major statin studies suggest an average 28% reduction in LDL cholesterol and a 31% reduction in relative risk, leaving a residual risk of about 69%. Incomplete reductions in risk, and failure to improve conditions that create risk, may result in ongoing progression of atherosclerosis, with new and recurring lesions in original and distant culprit sites, remodeling, arrhythmias, rehospitalizations, invasive procedures, and terminal disability. As a result, identification of additional agents to reduce residual risk, particularly administered together with statin drugs, has been an ongoing quest. The current model of atherosclerosis involves many steps during which disease may progress independently of guideline-defined elevations in LDL cholesterol. Differences in genetic responsiveness to statin therapy, differences in ability of the endothelium to regenerate and repair, and differences in susceptibility to nonlipid risk factors, such as tobacco smoking, hypertension, and molecular changes associated with obesity and diabetes, may all create residual risk. A large number of inflammatory and metabolic processes may also provide eventual therapeutic targets to lower residual risk. Classically, epidemiologic and other evidence suggested that raising high-density lipoprotein (HDL) cholesterol would be cardioprotective. When LDL cholesterol is aggressively lowered to targets, low HDL cholesterol levels are still inversely related to MCVE. The efflux capacity, or ability to relocate cholesterol out of macrophages, is believed to be a major antiatherogenic mechanism responsible for reduction in MCVE mediated in part by healthy HDL. HDL cholesterol is a complex molecule with antioxidative, anti-inflammatory, anti-thrombotic, antiplatelet, and vasodilatory properties, among which is protection of LDL from oxidation. HDL-associated paraoxonase-1 has a major effect on endothelial function. Further, HDL promotes endothelial repair and progenitor cell health, and supports production of nitric oxide. HDL from patients with cardiovascular disease, diabetes, and autoimmune disease may fail to protect or even become proinflammatory or pro-oxidant. Mendelian randomization and other clinical studies in which raising HDL cholesterol has not been beneficial suggest that high plasma levels do not necessarily reduce cardiovascular risk. These data, coupled with extensive preclinical information about the functional heterogeneity of HDL, challenge the "HDL hypothesis", ie, raising HDL cholesterol per se will reduce MCVE. After the equivocal AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides: Impact on Global Health Outcomes) study and withdrawal of two major cholesteryl ester transfer protein compounds, one for off-target adverse effects and the other for lack of efficacy, development continues for two other agents, ie, anacetrapib and evacetrapib, both of which lower LDL cholesterol substantially. The negative but controversial HPS2-THRIVE (the Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events) trial casts further doubt on the HDL cholesterol hypothesis. The growing impression that HDL functionality, rather than abundance, is clinically important is supported by experimental evidence highlighting the conditional pleiotropic actions of HDL. Non-HDL cholesterol reflects the cholesterol in all atherogenic particles containing apolipoprotein B, and has outperformed LDL cholesterol as a lipid marker of cardiovascular risk and future mortality. In addition to including a measure of residual risk, the advantages of using non-HDL cholesterol as a primary lipid target are now compelling. Reinterpretation of data from the Treating to New Targets study suggests that better control of smoking, body weight, hypertension, and diabetes will help lower residual risk. Although much improved, control of risk factors other than LDL cholesterol currently remains inadequate due to shortfalls in compliance with guidelines and poor patient adherence. More efficient and greater use of proven simple therapies, such as aspirin, beta-blockers, angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers, combined with statin therapy, may be more fruitful in improving outcomes than using other complex therapies. Comprehensive, intensive, multimechanistic, global, and national programs using primordial, primary, and secondary prevention to lower the total level of cardiovascular risk are necessary.
3.
Is prevention a fantasy, or the future of medicine? A panoramic view of recent data, status, and direction in cardiovascular prevention.
Kones, R
Therapeutic advances in cardiovascular disease. 2011;(1):61-81
Abstract
Americans are under assault by a fierce epidemic of obesity, diabetes, and cardiovascular disease, of their own doing. Lowered death rates from heart disease and reduced rates of smoking are seriously threatened by the inexorable rise in overweight and obesity. Latest data indicate that 32% of children are overweight or obese, and fewer than 17% exercise sufficiently. Over 68% of adults are overweight, 35% are obese, nearly 40% fulfill criteria for the metabolic syndrome, 8-13% have diabetes, 34% have hypertension, 36% have prehypertension, 29% have prediabetes, 15% of the population with either diabetes, hypertension, or dyslipidemia are undiagnosed, 59% engage in no vigorous activity, and fewer than 5% of the US population qualifies for the American Heart Association (AHA) definition of ideal cardiovascular health. Health, nutrition, and exercise illiteracy is prevalent, while misinformation and unrealistic expectations are the norm. Half of American adults have at least one cardiovascular risk factor. Up to 65% do not have their conventional risk biomarkers under control. Of those patients with multiple risk factors, fewer than 10% have all of them adequately controlled. Even when patients are treated according to evidence-based protocols, about 70% of cardiac events remain unaddressed. Undertreatment is also common. Poor patient adherence, probably well below 50%, adds further difficulty in reducing cardiovascular risk. Available data indicate that only a modest fraction of the total cardiovascular risk burden in the population is actually now being eliminated. A fresh view of these issues, a change in current philosophy, leading to new and different, multimechanistic methods of prevention may be needed. Adherence to published guidelines will improve substantially outcomes in both primary and secondary prevention. Primordial prevention, which does not allow risk values to appear in a population, affords more complete protection than subsequent partial reversal of elevated risk factors or biomarkers. Current evidence supports recent calls for massive educational programs supporting primordial prevention, individual responsibility and pride in achieving population-wide ideal cardiovascular health through lifestyle modification. Environmental and social changes will be necessary, along with major supportive adjustments in the food industry and the assistance of the media. Cooperation is critical to the success of such an initiative.