Showing papers by "Charles H. Hennekens published in 2016"

High- or Standard-Dose Influenza Vaccine for Middle-Aged Adults with Cardiovascular Disease: What's a Doctor to Do?

Abstract: plications from influenza is especially high [7] . Numerous studies suggest that influenza increases the risk of clinical CVD events, including as a trigger for acute myocardial infarction [8] . As a result, numerous guideline committees worldwide recommend an influenza vaccine to reduce recurrent CVD events [9] . Atherosclerosis, the principal underlying cause of CVD, is a progressive and chronic process that involves inflammation [10] . Inflammatory cells are involved in promoting plaque disruption and subsequent thrombus formation, the principal proximate cause of clinical CVD events [11] . In mice, the influenza virus itself produces inflammatory and thrombotic effects within 10 days [12] . Most guidelines recommend the trivalent, inactivated, high-dose influenza vaccine for all CVD patients over 65 years of age. The current influenza vaccines produce immunity against hemagglutinin and neuraminidase proteins present in virus strains. Researchers utilize two approaches in creating a universal influenza vaccine. One method involves preventing infection by generating antibody responses to the stalk region of the hemagglutinin protein. When the antibodies are neutralized, they cannot find the receptors on the cells or fuse with the cell memIn contrast to the epidemics of influenza which occur regularly every season with relatively low mortality rates, pandemics occur irregularly with high mortality rates. In this regard, the 1918 Spanish flu pandemic may have been the most serious in recorded history, causing 50–100 million deaths. There have been about three influenza pandemics in each century for the last 300 years, the most recent being the 2009 flu pandemic [1] . In contrast, during the last 50 years, cardiovascular disease (CVD) has remained the leading cause of death among men and women in the USA, causing 1 in 3 or about 800,000 fatalities each year [2, 3] . In addition, CVD is rapidly becoming the leading cause of death worldwide. Although advancing age becomes the most powerful risk factor, about 62% of patients with CVD are under the age of 65 years. Among adults aged between 55 and 64 years, 52.0% of men and 56.5% of women have one or more clinical manifestation of CVD [4] . The annual direct and overall costs attributed to CVD are estimated at USD 273 billion and USD 444 billion, respectively [5] . With regard to influenza in the USA, at present, this disease causes about 35,000 deaths and 225,000 hospitalizations annually [6] . For patients with CVD the risk of death and serious comReceived: September 30, 2015 Accepted: October 8, 2015 Published online: December 1, 2015

Prolonged QTc Interval and Risks of Total and Cardiovascular Mortality and Sudden Death in the General Population

Abstract: Methods: We conducted a literature search from 1990 forwardtoidentifyallpublishedprospectivecohortstudiesevaluatingtheassociationbetweenprolongedQTcinterval and risks of total and cardiovascular mortality as well as sudden death. We reviewed each of the studies individually and then conducted a qualitative overview. Results:The7prospectivecohortstudiesidentifiedincluded 36031individuals.Therewere2677(8.7%)individualswith prolonged QTc interval, defined as 440 milliseconds or greater.Whereas1studyreportednoassociationbetween prolonged QTc interval and mortality (relative risk, 1.02; 95% confidence interval, 0.70-1.49), the other 6 reported inconsistentassociationsoverallaswellasacrosssubgroups defined by various characteristics including age, sex, and comorbidities. The reported associations for both cardiovascularmortalityandsuddendeathwerealsoinconsistent. In the overview, the only consistent findings were for the subgroupofpatientswithpriorcardiovasculardisease,in which relative risks ranged from 1.1 to 3.8 for total mortality,from1.2to8.0forcardiovascularmortality,andfrom 1.0 to 2.1 for sudden death. Further, in individuals without prior cardiovascular disease, associations were either absentorgreatlyattenuated;specifically,relativerisksranged from 0.9 to 1.6 for total mortality, from 1.2 to 1.7 for cardiovascularmortality,andfrom1.3to2.4forsuddendeath. Conclusions:Therewasnoconsistentevidenceforincreased risksoftotalorcardiovascularmortalityorofsuddendeath, except perhaps for patients with prior cardiovascular disease. In the general population, if QTc interval prolongation is associated with any increase in mortality, that risk is likely to be small and difficult to detect reliably. Arch Intern Med. 2004;164:943-948