Heart Rate as a Risk Factor for Cardiovascular Disease

Almost all the epidemiological studies that aimed to answer the question of the relationship between heart rate and all-cause or cardiovascular morbidity and mortality reported that a high heart rate was associated with a higher risk of all-cause mortality and cardiovascular events. This relationship has been found to be generally stronger in men than among women. The increase in the cardiovascular risk, associated with the acceleration of heart rate, was comparable to the increase in risk observed with high blood pressure. It has been shown that an increase in heart rate by 10 beats per minute was associated with an increase in the risk of cardiac death by at least 20%, and this increase in the risk is similar to the one observed with an increase in systolic blood pressure by 10 mm Hg. It has also been shown that heart rate recorded in elderly men has a strong predictive value in survival to a very old age. Taken together, these results indicate that the risk associated with accelerated heart rate is not only statistical significant but also clinically relevant and that it should be taken into account in the evaluation of the patients. Although the association between elevated heart rate and cardiovascular morbidity and mortality has been demonstrated in a large number of epidemiological studies, tachycardia has remained a neglected cardiovascular risk factor until very recently. For the first time, the recent guidelines of the European Society of Cardiology and the European Society of Hypertension indicate than an accelerated heart rate is considered as an independent risk factor and potentially as a target for pharmacologic therapies, especially in high-risk patients.     

Cholesterol in the prediction of atherosclerotic disease. New perspectives based on the Framingham study.

Prospective data at Framingham and elsewhere have shown conclusively that risk of coronary heart disease in persons younger than age 50 is strikingly related to the serum total cholesterol level. Within so-called normal limits risk has been found to mount over a five-fold range. The impact has been found to be augmented by other risk factors. The contribution of the serum total cholesterol to risk has also been found to be determined by its partition in the various lipoprotein fractions. A relatively large amount of cholesterol in the low-density lipoprotein fraction is atherogenic, whereas that in the high-density fraction appears protective. The independent contribution of very-low density lipoprotein and its triglyceride or cholesterol content has, on the other hand, not been established. The previous position that virtually all of the lipid information pertaining to coronary heart disease resided in the serum total cholesterol must be accordingly modified.     

Risk Factor Variability and Cardiovascular Outcome: JACC Review Topic of the Week

Until recently, intraindividual visit-to-visit variability of cardiovascular risk factors has been dismissed as random fluctuation. This simplistic concept was challenged by demonstrating that visit-to-visit blood pressure variability, independent of average blood pressure, was a powerful risk factor for stroke. Subsequently, variability of other cardiovascular risk factors such as cholesterol, glycemia, and body weight was documented to increase risk independent of their absolute values. Variability of these risk factors has been demonstrated to be a powerful predictor for all-cause and cardiovascular mortality, stroke, coronary artery disease, heart failure, end-stage renal disease, and dementia. With the notable exception of heart rate, cardiovascular risk factors must now be defined by 2 components: the magnitude and duration of sustained risk factor elevation and, equally important, the variability of the same risk factor over time.     

Gambling With Cardiovascular Disease Risk Models: How to Choose and How to Use

Cardiovascular risk assessment has been shown to improve physicians’ and patients’ understanding of an individual’s future risk of cardiovascular disease (CVD). It has also been shown to improve the management of cardiovascular risk factors including hypertension and dyslipidemia. Given the challenges of engaging patients to adhere to healthy lifestyle habits or take medications for hypertension and dyslipidemia, the primary role of CVD risk assessment should be to open a discussion about the patient’s risk for CVD and associated conditions like adult-onset diabetes. Calculating a patient’s long-term risk and estimating the benefits of lifestyle changes or risk factor management may then be used to support long-term patient adherence. However, risk assessment is only a first step and must be followed by evidence-based health-promotion strategies and risk factor medications that have been proven to work.     

Coronary heart disease risk factors in the elderly

Hypertension, dyslipidemia, impaired glucose tolerance, and obesity remain the major modifiable risk factors for most of the coronary disease afflicting the elderly. The relative risk associated with these established risk factors diminishes with advancing age, but this is offset by a greater absolute and attributable risk. Diabetes is increasing alarmingly in prevalence and operates more powerfully in women, eliminating their coronary disease resistance (relative to men). Interest in this entity now focuses on the insulin resistance syndrome promoted by abdominal obesity that has become so common in the elderly. The isolated systolic hypertension and large pulse pressure that predominate in the elderly is now recognized as a coronary disease hazard. Dyslipidemia, characterized by a high total to high-density lipoprotein cholesterol ratio, is the most predictive lipid profile for coronary disease in the elderly. High triglycerides, accompanied by low high-density lipoprotein cholesterol usually signifies insulin resistance and more atherogenic, small, dense low-density lipoprotein. Left ventricular hypertrophy is an ominous harbinger of coronary disease. Fibrinogen and the leukocyte count are correlated coronary disease risk factors that may indicate unstable lesions. Novel risk factors, such as hemostatic factors, homocysteine, lipoprotein(a), C-reactive protein, and hyperinsulinemia, are worthy of attention, but the efficacy of correcting them in the elderly has not yet been demonstrated. Nor has the efficacy of hormone replacement therapy in women. All the coronary risk factors tend to cluster, and the hazard posed by each is greatly influenced by the burden of coexisting risk factors. High-risk elderly candidates for coronary disease can be efficiently targeted for treatment by global risk assessment, using only the major established risk factors. The distinction between primary and secondary prevention in the elderly is less clear than in the middle-aged because they often have advanced presymptomatic vascular pathology that imposes a coronary event rate comparable to that of the middle-aged who have already sustained a clinical event. Declines in coronary mortality rates in the United States have included the elderly, justifying optimism about the efficacy of preventive measures. Most of the elderly have sufficient remaining life expectancy to warrant vigorous preventive management. Trials of risk factor modification in the elderly indicate that decades of exposure to modifiable risk factors can be countered by measures implemented late in life.     

The role of ambulatory monitoring in assessing cardiac risk in peripheral vascular surgery.

Patients undergoing vascular surgery have a uniformly higher risk for postoperative cardiac events, and this risk has traditionally been difficult to quantify. Research has focused on the addition of noninvasive testing to the preoperative assessment of patients at moderate risk by clinical criteria. Current data suggest that preoperative ambulatory monitoring successfully identifies risk for cardiac events in patients undergoing vascular surgery and represents a practical alternative, particularly when patients cannot exercise. Postoperative monitoring appears to be particularly useful in heralding cardiac events in high-risk patients with enough lead time to make prophylactic and preemptive intervention feasible.     

Importance of blood glucose management in the multifactorial approach of absolute cardiovascular risk in type 2 diabetes: the lessons from the Steno 2 Study

The problem of blood glucose as a cardiovascular risk factor has long been debated. Indeed, increasing arguments confirm the importance of blood glucose on cardiovascular risk, as shown by the results from epidemiological studies and therapeutic investigations. However, the literature has demonstrated the importance of postprandial blood glucose, or post-load-glucose, on cardiovascular risk. One could think that blood glucose, in particular postprandial blood glucose, is an independent, although not major, cardiovascular risk factor compared to other classical risk factors such as hypercholesterolemia, high blood pressure, and smoking, but it potentiates the risk when it coexists with these classical risk factors. This explains the increased prevalence of cardiovascular morbi-mortality in diabetic patients, in particular type 2 diabetes. Multifactorial treatment can reduce the cardiovascular risk by 55%, as the Steno 2 study demonstrated.     

Importance of left ventricular mass as a predictor of cardiovascular morbidity in hypertension

Arterial hypertension is a powerful risk factor for cardiovascular disease, but the ability to use blood pressure measurements to predict complications in individual patients or small groups is limited. One possible approach to identifying hypertensive patients at high risk is based on the observation that the presence of electrocardiographic left ventricular hypertrophy (ECG-LVH) identifies individuals at severalfold higher risk than other individuals with similar blood pressure but no ECG-LVH. The suggestion that the increased risk associated with ECG-LVH is related to increased left ventricular (LV) mass has been supported by autopsy studies in which heart weight was found to be increased in patients dying of cardiovascular diseases. Unfortunately, the usefulness of LVH to predict prognosis in hypertension has been limited practically by the fact that ECG-LVH is present in only 3% to 8% of average hypertensive patients, and by the possibility that certain electrocardiographic patterns, particularly involving repolarization, might reflect undiagnosed coronary artery disease rather than myocardial hypertrophy. The development over the past dozen years of anatomically validated echocardiographic methods of measuring LV muscle mass has provided a probe that is more sensitive than electrocardiography for detection of hypertensive LVH. This method has now been utilized in studies which suggest that LV mass may be more important than blood pressure as a predictor and possible determinant of cardiovascular morbid events. It is the purpose of this review to evaluate critically these findings and other clinical and experimental evidence related to the prognostic significance and possible mechanisms of risk associated with increased LV mass.     

Insights into disparities observed with COVID-19

The onset of human disease by infection with SARS-CoV-2 causing COVID-19 has revealed risk factors for disease severity. There are four identified factors that put one at high risk for infection and/or mortality creating a disparity: age, co-morbidities, race/ethnicity and gender. Data indicate that the older a person is, and/or the presence of obesity and diabetes, cardiovascular disease and chronic kidney disease place one at higher risk for COVID-19. In the United States, specific race/ethnicities, particularly African Americans and Native Americans, are strong COVID-19 risk components. Male gender has also emerged as a severity risk factor. For age and racial/ethnicities, the accumulation of health co-morbidities is common precipitating mechanisms. In particular, underlying socio-economic structures in the United States likely drive development of co-morbidities, putting affected populations at higher risk for severe COVID-19. Sudden cardiac death triggered by a common sodium channel variant in African Americans with COVID-19 has not been evaluated as a cause for racial disparity. There is no evidence that racial/ethnic differences for COVID-19 are caused by ABO blood groups, use of angiotensin-converting enzyme (ACE) inhibitors or from amino acid substitutions in the SARS-CoV-2 spike protein. There is growing evidence that androgen-enabled expression of ACE2 receptors and the serine protease TMPRSS2, two permissive elements engaging the SARS-CoV-2 spike protein for infection, may contribute to severe COVID-19 in men. Overall, COVID-19 has generated disparities for who is infected and the severity of that infection. Understanding the mechanisms for the disparity will help nullify the differences in risk for COVID-19.     

Genotyping in Prothrombotic States: Implications for the Clinician

Thrombophilia has been subject to extensive genetic research. This review focuses on the genetic variants that have confirmed associations with venous thrombosis (VT). For incident VT, the early discovery of variants with large-magnitude associations, such as mutations in antithrombin, protein C, and protein S genes, has been followed by genetic variants that are associated with more moderate risk, such as the factor V Leiden, and prothrombin G20210A. More recently, large candidate-gene and genome-wide association studies have discovered multiple genetic variants with generally weak association with VT. For recurrent VT, the evidence for genetic risk factors remains very limited. Although thrombophilia testing is broadly available to clinicians, the impact on the clinical management of patients remains modest and depends on the strength of the association with VT. More promising for clinical practice may be global assessments of risk that combine risk information from multiple genetic variants, or with those from acquired risk factors. These models have yet to be defined and tested in large and diverse populations to demonstrate that this new genetic risk information has clinical applicability and improves health outcomes.     

The Framingham Risk Score: an appraisal of its benefits and limitations

The concepts of risk assessment and reduction are the cornerstones of preventive cardiology practice. The Framingham Heart Study is a landmark achievement that has provided valuable insights into coronary heart disease risk prediction. Through this cohort study, risk calculators have been generated to predict the risk of cardiac disease in asymptomatic patients. These risk predictors are practical, clinically relevant, and modestly accurate. Their accuracy is somewhat limited in applicability among certain specific populations, however, and some well-known risk factors are not incorporated. These are recognized limitations of the Framingham Risk Score, but it is important to keep in mind that the Framingham Heart Study is an ongoing project and that there are new risk prediction models forthcoming to incorporate additional risk factors. The emergence of subclinical atherosclerosis testing offers promise to refine the assessment of global risk, specifically identifying subjects assessed as intermediate risk by the standard Framingham Risk Score.     

New clinical markers predictive of cardiovascular disease: the role of inflammatory mediators

Identification of persons at risk for developing cardiovascular disease has focused attention on blood pressure, smoking, and serum cholesterol levels. Modification of these factors has resulted in reduction of overall morbidity and mortality within the population. While significant, these risk factors do not predict all cardiovascular events, because the causes of cardiovascular disease are multifactorial and the risk associated with any given factor is compounded by the presence of other risk factors. Additional risk factors that may also identify risk for cardiovascular disease may include inflammatory mediators such as C-reactive protein, interleukin 6, cell adhesion molecules, and fibrinogen. Although additional studies are needed to establish the clinical utility of these markers, they may improve the identification and assessment of patients at risk for future cardiovascular events.     

Estimating the year of eradication of tuberculosis in Japan]

The time of eradication of tuberculosis has been discussed for several countries, and based on those results, a new strategic plan and goals have been elaborated. Considering such developments, and in order to make a new tuberculosis control strategy, it is important to determine the point at which eradication of tuberculosis would be achieved in Japan. Styblo proposed the two conventional definitions of eradication of tuberculosis, namely that the incidence of smear-positive tuberculosis has fallen below 1 per million population or that the prevalence of tuberculosis infection in the general population has fallen below 1% and continues to decrease. The bacteriological results of new cases have been reported since 1975 in Japan. However, those results are still of doubtful validity and reliability. Therefore, the author estimated the year of eradication of tuberculosis, according to the criterion that tuberculosis is eradicated when the proportion of the population infected with tubercle bacilli is less than 1%. If the risk of infection is changing at a regular rate, it is possible to estimate the risk of infection at any time in the past and in the future. Once the risk of infection is determined, it is also possible to calculate the age-specific prevalence of infection and the proportion of the population infected with tubercle bacilli at various times in the past and in the future. In Japan, the risk of infection before World War II was assumed to be around 4% and not to vary with calendar year. And based on the data from the prevalence surveys in Okinawa in 1968 and 1973, the risk of infection was estimated 0.3% in 1968 and has declined on average, by 10 to 11% annually. At that time, Okinawa was the only area free from BCG vaccination in Japan. The incidence rate in Japan also has declined, on average, by 10% annually. However, since late 1970s, the annual speed of decline of the incidence rate has been slowed down. Therefore, I assumed that the recent trend of the infection risk is the same as the trend of the recent incidence rate among the 0-29 year age-group. The size of the effect of age on the risk of infection has been discussed. The author also considered age-effects in the model. The weight applied to the risk of infection by age was determined by examining the age-specific positive rate in the 1930s before the era when BCG vaccination was widely used.(ABSTRACT TRUNCATED AT 400 WORDS)     

Secondary prophylaxis of venous thromboembolism

Making decisions about any modality of secondary prophylaxis in patients with venous thromobembolism (VTE) has to balance the risk of bleeding induced by anticoagulants against the benefit of reducing the risk of recurrent disease. It has to be kept in mind that the magnitude of risk is not only defined by the number of events per time period but also by the impact of the event on the fate of the patient. With standard intensity Vitamin K antagonists, the risk of bleeding is more closely related to comorbidities than to other factors, e.g. age. The risk of VTE recurrence differs largely between patient groups. The criterion of presence, or absence of a permanent or transient clinical trigger factor for the actual VTE episode has a greater impact than an abnormal result in thrombophilia testing. The standard period ofsecondary prophylaxis for proximal deep vein thrombosis and for pulmonary embolism is three to six months. The concept of prolonging this period for several months according to the risk of recurrence is seriously challanged by the observation that the prolongation period seems to delay recurrencies rather than truly avoiding them. For this reason, patients who clearly are threatened by recurrent episodes should receive indefinitive secondary prophylaxis. This is the case for cancer patients, patients with the antiphospholipid syndrome, and those who belong to families with severe and symptomatic protein C, protein S, or antithrombin deficiencies. Patients with recurrent VTE, with idiopathic VTE, or with combined thrombophilic conditions may only benefit from indefinitive secondary prophylaxis if the bleeding risk of the anticoagulant regimen under consideration is very low.     

Contrast echocardiography in acute myocardial ischemia. II. The effect of site of injection of contrast agent on the estimation of area at risk for necrosis after coronary occlusion

Myocardial contrast echocardiography has been shown to accurately assess the area at risk for necrosis after acute coronary occlusion in the experimental model. The area at risk as determined by this method, however, has been defined in different ways depending on the model used. Some investigators have injected the contrast agent proximal to the site of coronary occlusion (left main coronary artery or aorta) and defined the area at risk as the segment of myocardium not showing a contrast effect (negative risk area). Others have injected the contrast agent directly into the occluded vessel and have defined the area at risk as that showing contrast enhancement (positive risk area). To evaluate whether the areas at risk determined by these two techniques are identical, six open chest dogs were studied using both methods. The area at risk was slightly but significantly larger when the contrast agent was injected into the occluded vessel than when it was injected proximally into the left main coronary artery (4.98 +/- 1.69 versus 3.97 +/- 1.27 cm2, p less than 0.01). It is concluded that the site of injection of the contrast agent significantly influences the determination of area at risk. Therefore, data obtained by the two techniques should not be used interchangeably, and in a given study the area at risk should be measured consistently using one technique.     

Atherosclerosis and inflammation

The pathophysiology of coronary atherosclerosis is complex and multifactorial. The probability of the development of symptomatic coronary heart disease may be predicted by standard risk factor stratification involving hypertension, dyslipidemia, age, positive family history, and diabetes. However, risk factor stratification has been demonstrated to have significant limitations in the individual patient, which has generated a search for more specific and sensitive markers. Evidence is increasing that atherosclerosis is a disease characterized by inflammation, beginning with the earliest identifiable lesion (fatty streak) to the advanced vulnerable plaque. Clinical markers of inflammation, including C-reactive protein, modified low-density lipoprotein, homocysteine, tumor necrosis factor, and thermogenicity, have been identified as emerging risk factors that may add prognostic information in patient management. This review centers on inflammation as a potential pathogenetic factor in atherosclerosis and the role that clinical markers may play in the identification of patients at risk.     

Labeling of participants in high blood pressure screening programs. Implications for blood cholesterol screenings

Screening programs have expanded to identify the many persons who are unaware of their high blood cholesterol level and thus are at an increased risk for coronary heart disease. These programs bring both potential benefits and potential risks to the participant. One potential risk is that of iatrogenic effects of learning one's risk status, often referred to as the "labeling phenomenon." Research that has addressed the labeling phenomenon in blood pressure screening programs has important implications for blood cholesterol screenings. Detrimental effects on screening participants are possible, but they can be attenuated by careful attention to characteristics of the debriefing and counseling that should be included in screening protocols.     

Gender differences in financial risk aversion and career choices are affected by testosterone

Women are generally more risk averse than men. We investigated whether between- and within-gender variation in financial risk aversion was accounted for by variation in salivary concentrations of testosterone and in markers of prenatal testosterone exposure in a sample of >500 MBA students. Higher levels of circulating testosterone were associated with lower risk aversion among women, but not among men. At comparably low concentrations of salivary testosterone, however, the gender difference in risk aversion disappeared, suggesting that testosterone has nonlinear effects on risk aversion regardless of gender. A similar relationship between risk aversion and testosterone was also found using markers of prenatal testosterone exposure. Finally, both testosterone levels and risk aversion predicted career choices after graduation: Individuals high in testosterone and low in risk aversion were more likely to choose risky careers in finance. These results suggest that testosterone has both organizational and activational effects on risk-sensitive financial decisions and long-term career choices.