Lower Risk Of Coronary Disease Research Articles

Ergothioneine is associated with reduced mortality and decreased risk of cardiovascular disease

ObjectivesWe recently identified a health conscious food pattern (HCFP) associated with reduced risk of cardiometabolic disease. However, the molecular events linking the healthy food pattern to reduced risk of cardiometabolic...

The Consumption of Alcoholic Beverages and the Prevalence of Cardiovascular Diseases in Men and Women: A Cross-Sectional Study.

Associations between alcohol consumption and the prevalence of cardiovascular diseases have been the subject of several studies for a long time; however, the presence and nature of any associations still remain unclear. The aim of the study was to analyze the associations between the consumption of alcoholic beverages and the prevalence of cardiovascular diseases in men and women. The data of 12,285 individuals aged 37–66 were used in the analysis. Multiple logistic regression models were utilized to estimate odds ratios and confidence intervals. The multivariable models included several potential confounders including age, education, marital status, body mass index (BMI), physical activity, smoking, coffee consumption, and statin use. The analyses were performed separately for men and women. In the model adjusted for confounders, the consumption from 0.1 to 10.0 g of alcohol/day was related to a lower risk of coronary disease and stroke (p < 0.05), and the consumption from 0.1 to 15.0 g/day was related to a lower risk of hypertension in women (p < 0.05). In men, in the adjusted model, there were no associations between alcohol consumption and the occurrence of hypertension or stroke. The risk of circulatory failure was significantly lower in the group in which participants drank more than 20.0 g of alcohol/day (p < 0.05) compared to nondrinkers. The risk of coronary disease was lower in drinkers at every level of alcohol consumption (p < 0.05) compared to nondrinkers. Alcohol consumption was related to a lower prevalence of cardiovascular diseases (CVD), both in men and women.

Association of Genetically Enhanced Lipoprotein Lipase–Mediated Lipolysis and Low-Density Lipoprotein Cholesterol–Lowering Alleles With Risk of Coronary Disease and Type 2 Diabetes

Pharmacological enhancers of lipoprotein lipase (LPL) are in preclinical or early clinical development for cardiovascular prevention. Studying whether these agents will reduce cardiovascular events or diabetes risk when added to existing lipid-lowering drugs would require large outcome trials. Human genetics studies can help prioritize or deprioritize these resource-demanding endeavors. To investigate the independent and combined associations of genetically determined differences in LPL-mediated lipolysis and low-density lipoprotein cholesterol (LDL-C) metabolism with risk of coronary disease and diabetes. In this genetic association study, individual-level genetic data from 392 220 participants from 2 population-based cohort studies and 1 case-cohort study conducted in Europe were included. Data were collected from January 1991 to July 2018, and data were analyzed from July 2014 to July 2018. Six conditionally independent triglyceride-lowering alleles in LPL, the p.Glu40Lys variant in ANGPTL4, rare loss-of-function variants in ANGPTL3, and LDL-C-lowering polymorphisms at 58 independent genomic regions, including HMGCR, NPC1L1, and PCSK9. Odds ratio for coronary artery disease and type 2 diabetes. Of the 392 220 participants included, 211 915 (54.0%) were female, and the mean (SD) age was 57 (8) years. Triglyceride-lowering alleles in LPL were associated with protection from coronary disease (approximately 40% lower odds per SD of genetically lower triglycerides) and type 2 diabetes (approximately 30% lower odds) in people above or below the median of the population distribution of LDL-C-lowering alleles at 58 independent genomic regions, HMGCR, NPC1L1, or PCSK9. Associations with lower risk were consistent in quintiles of the distribution of LDL-C-lowering alleles and 2 × 2 factorial genetic analyses. The 40Lys variant in ANGPTL4 was associated with protection from coronary disease and type 2 diabetes in groups with genetically higher or lower LDL-C. For a genetic difference of 0.23 SDs in LDL-C, ANGPTL3 loss-of-function variants, which also have beneficial associations with LPL lipolysis, were associated with greater protection against coronary disease than other LDL-C-lowering genetic mechanisms (ANGPTL3 loss-of-function variants: odds ratio, 0.66; 95% CI, 0.52-0.83; 58 LDL-C-lowering variants: odds ratio, 0.90; 95% CI, 0.89-0.91; P for heterogeneity = .009). Triglyceride-lowering alleles in the LPL pathway are associated with lower risk of coronary disease and type 2 diabetes independently of LDL-C-lowering genetic mechanisms. These findings provide human genetics evidence to support the development of agents that enhance LPL-mediated lipolysis for further clinical benefit in addition to LDL-C-lowering therapy.

Value of CACS Compared With ETT and Myocardial Perfusion Imaging for Predicting Long-Term Cardiac Outcome in Asymptomatic and Symptomatic Patients at Low Risk for Coronary Disease: Clinical Implications in a Multimodality Imaging World

ObjectivesThis prospective, observational study in 988 asymptomatic or symptomatic low-risk patients without prior coronary artery disease was conducted to define the relative value of coronary artery calcium score (CACS), exercise treadmill testing (ETT), and stress myocardial perfusion single-photon emission computed tomography (SPECT) variables in predicting long-term risk stratification. BackgroundCACS, ETT, and stress myocardial perfusion SPECT results predict patients' outcome. There are currently no data comparing their relative value in long-term risk stratification. MethodsPatients were stratified by Framingham risk score (FRS), with a median follow-up of 6.9 years. Cardiac events were defined as a composite of cardiac death, nonfatal myocardial infarction, and the need for coronary revascularization. Most patients (87%) were considered appropriate candidates for functional testing as defined by current appropriate use criteria. ResultsThe long-term cardiac event rate was 11.2% (1.6% per year). Multivariate risk predictors in all patients and in the appropriate use cohort were abnormal SPECT (hazard ratio [HR]: 1.83 and 1.99), ETT ischemia (HR: 1.70 and 1.76), decreasing exercise capacity (HR: 1.11 and 1.17), decreasing Duke treadmill score (HR: 1.07 for both), and CACS severity (HR: 1.29 for both), respectively. Throughout the 10-year follow-up, CACS improved risk prediction, with event rates ranging from 0.6% per year (CACS ≤10) to 3.7% per year (CACS >400) (p < 0.0001). CACS also improved risk prediction in all patients, in the appropriate use cohort and among those with low-risk ETT and SPECT results (all, p < 0.001). Area under the receiver-operating characteristic curve was increased when CACS variables (from 0.63 to 0.70; p = 0.01) but not ETT variables (from 0.63 to 0.65) were added to FRS. Moreover, net reclassification improvement was significantly increased when CACS was added to FRS + functional variables in all patients and in the appropriate use cohort (both, p < 0.0001). ConclusionsCACS significantly improved long-term risk stratification beyond FRS, ETT, and SPECT results across the spectrum of clinical risk and importantly even among those who are currently considered appropriate candidates for functional testing or have low-risk functional test results. Our findings support CACS as a first-line test over ETT or SPECT for accurately assessing long-term risk in such patients.

Statin cost effectiveness in primary prevention: A systematic review of the recent cost-effectiveness literature in the United States

BackgroundThe literature on the cost-effectiveness of statin drugs in primary prevention of coronary heart disease is complex. The objective of this study is to compare the disparate results of recent cost-effectiveness analyses of statins.FindingsWe conducted a systematic review of the literature on statin cost-effectiveness. The four studies that met inclusion criteria reported varying conclusions about the cost-effectiveness of statin treatment, without a clear consensus as to whether statins are cost-effective for primary prevention. However, after accounting for each study’s assumptions about statin costs, we found substantial agreement among the studies. Studies that assumed statins to be more expensive found them to be less cost-effective, and vice-versa. Furthermore, treatment of low-risk groups became cost-effective as statins became less expensive.ConclusionsDrug price is the primary determinant of statin cost-effectiveness within a given risk group. As more statin drugs become generic, patients at low risk for coronary disease may be treated cost-effectively. Though many factors must be weighed in any medical decision, from a cost-effectiveness perspective, statins may now be considered an appropriate therapy for many patients at low risk for heart disease.

Preoperative Visualization of an Atrial Septal Defect by 64-Slice Cardiac Computed Tomography

A 55-year-old woman with no prior cardiac history was referred for echocardiography after a precordial murmur was discovered on routine physical examination. Transthoracic and later transesophageal (Figure ​(Figure11) echocardiography revealed a secundum-type atrial septal defect (ASD) measuring 1 cm in diameter and mild mitral regurgitation with normal ejection fraction and no wall motion abnormalities. Because of her low risk for coronary disease, a cardiac computed tomography (CT) scan was done both to localize the ASD and to confirm the lack of significant coronary atherosclerosis (Figure ​(Figure22). Figure 1 Transesophageal echocardiography demonstrating a large atrial septal defect. (a) Doppler interrogation demonstrates left atrium (LA) to right atrium flow of blood (arrow). (b) The atrial septal defect measured approximately 0.9 × 1.2 cm and was ... Figure 2 Cardiac computed tomography demonstrating (a) no coronary anomalies and (b) no significant soft or calcified plaque in the coronary lumen. (c) There was confirmation of an enlarged right ventricle (RV), as seen in the axial images of the heart. (d) Navigator ... Intraoperatively, the secundum-type ASD was confirmed and repaired with no intraoperative or postoperative complications. She was discharged on hospital day 5 in good condition. We and others have previously described the utilization of 64-slice cardiac CT to effectively rule out coronary disease in low-probability patients scheduled for cardiac operations, including removal of an intracardiac tumor, closure of a ventricular septal defect, and valve repair or replacement (1–4). Additionally, CT has been described as a helpful adjunctive imaging test to evaluate the size and location of an ASD as well as in evaluating the impact of the ASD on right atrial and right ventricular chamber size (5, 6). This case is another example of the utility of 64-slice coronary CT to rule out significant coronary disease in a low-risk individual scheduled for cardiac surgery, sparing them additional preoperative invasive procedures.

Optimisation of strain rate imaging for application to stress echocardiography

We sought to improve the feasibility of strain rate imaging (SRI) during dobutamine stress echocardiography (DSE) in 56 subjects at low risk of coronary disease. The impact of several SRI changes during acquisition were studied, including: (1) changing from fundamental to harmonic imaging; (2) parallel beamforming; (3) alteration of spatial resolution and (4) narrow sector acquisition. We assessed SR signal quality, a quantitative measure of signal noise and measurements of SRI. Of 1462 segments evaluated, 6% were uninterpretable at rest and 8% at peak stress. Signal quality was optimised by increasing temporal (p = 0.01) and spatial resolution (p < 0.0001 vs. baseline imaging) at rest and peak. Increasing spatial resolution also minimised signal noise (p < 0.0001). Inter-observer variability of time to peak SR and peak SR were less with high temporal and spatial resolution. SRI quality can be improved with harmonic imaging and higher temporal resolution but optimisation of spatial resolution is critical. (E-mail: tmarwick@soms.uq.edu.au)

Effects of cholesterol-lowering with simvastatin on stroke and other major vascular events in 20 536 people with cerebrovascular disease or other high-risk conditions

Lower blood cholesterol concentrations have consistently been found to be strongly associated with lower risks of coronary disease but not with lower risks of stroke. Despite this observation, previous randomised trials had indicated that cholesterol-lowering statin therapy reduces the risk of stroke, but large-scale prospective confirmation has been needed. 3280 adults with cerebrovascular disease, and an additional 17256 with other occlusive arterial disease or diabetes, were randomly allocated 40 mg simvastatin daily or matching placebo. Subgroup analyses were prespecified of first "major vascular event" (ie, non-fatal myocardial infarction or coronary death, stroke of any type, or any revascularisation procedure) in prior disease subcategories. Subsidiary outcomes included any stroke, and stroke sub-type. Comparisons are of all simvastatin-allocated versus all placebo-allocated participants (ie, "intention-to-treat"), which yielded an average difference in LDL cholesterol of 1.0 mmol/L (39 mg/dL) during the 5-year treatment period. Overall, there was a highly significant 25% (95% CI 15-34) proportional reduction in the first event rate for stroke (444 [4.3%] simvastatin vs 585 [5.7%] placebo; p<0.0001), reflecting a definite 28% (19-37) reduction in presumed ischaemic strokes (p<0.0001) and no apparent difference in strokes attributed to haemorrhage (51 [0.5%] vs 53 [0.5%]; rate ratio 0.95 [0.65-1.40]; p=0.8). In addition, simvastatin reduced the numbers having transient cerebral ischaemic attacks alone (2.0% vs 2.4%; p=0.02) or requiring carotid endarterectomy or angioplasty (0.4% vs 0.8%; p=0.0003). The reduction in stroke was not significant during the first year, but was already significant (p=0.0004) by the end of the second year. Among patients with pre-existing cerebrovascular disease there was no apparent reduction in the stroke rate, but there was a highly significant 20% (8-29) reduction in the rate of any major vascular event (406 [24.7%] vs 488 [29.8%]; p=0.001). The proportional reductions in stroke were about one-quarter in each of the other subcategories of participant studied, including: those with coronary disease or diabetes; those aged under or over 70 years at entry; and those presenting with different levels of blood pressure or lipids (even when the pretreatment LDL cholesterol was below 3.0 mmol/L [116 mg/dL]). Much larger numbers of people in the present study suffered a stroke than in any previous cholesterol-lowering trial. The results demonstrate that statin therapy rapidly reduces the incidence not only of coronary events but also of ischaemic strokes, with no apparent effect on cerebral haemorrhage, even among individuals who do not have high cholesterol concentrations. Allocation to 40 mg simvastatin daily reduced the rate of ischaemic strokes by about one-quarter and so, after making allowance for non-compliance in the trial, actual use of this regimen would probably reduce the stroke rate by about a third. HPS also provides definitive evidence that statin therapy is beneficial for people with pre-existing cerebrovascular disease, even if they do not already have manifest coronary disease.

Dietary Supplement Use in the Context of Health Disparities: Cultural, Ethnic and Demographic Determinants of Use

Women of African American, Hispanic, Asian, Pacific Islander, Native American and Alaskan descent constitute 29% of the female population in the United States but they experience health problems disproportionately. Compared with white women as a group, they are in poorer health and use fewer health services. We know from recent studies that the daily use of multivitamins has been associated with lower risk of coronary disease, colon cancer and breast cancer, particularly for alcohol drinkers. In addition, daily multivitamin and multimineral usage by the elderly can reduce the number of days of illness due to infections by 50%. However, supplement use among women tends to be more prevalent among the middle and older age categories; white, well-educated and higher income women; and those residing in the western part of the United States. This examination of the current health disparities and usage patterns indicates that the women who could benefit most from supplements are not typical users. Qualitative data collected on iron and folic acid supplementation programs in developing countries indicate that diverse cultural practices, attitudes and beliefs among vulnerable populations may influence supplement use. However, data in the U.S literature that describe these factors by culture or ethnicity are sparse. If we are to promote dietary supplements to women who are most vulnerable, more research is warranted in the area of health beliefs, attitudes and sociodemographic determinants of supplement use by culture and or ethnicity, particularly among underprivileged groups.

A Prospective Study of Vitamin E and Coronary Heart Disease Among Men:

0016 A growing body of evidence suggests that oxidative modification of LDL-cholesterol is important in the early development of atherosclerotic lesions. Although past observational epidemiologic evidence suggests CHD benefit for long term vitamin E supplement use, two recent large secondary prevention trials have not found a lower risk of CVD among patients randomized to vitamin E. Data comparing the benefits of vitmain E between populations with and without prior CVD have not been adequately explored. We examined prospectively the association between vitamin E supplements (&gt;100 IU/day for 2 or more years) and risk of coronary heart disease among 38,884 U.S. male health professionals, 40 to 75 years of age at baseline (1986) and who were free of diagnosed CVD, diabetes, and cancer. During ten years of follow-up, we documented 1145 incident cases of fatal and non-fatal myocardial infarction (MI). After controlling for several known coronary risk factors, we observed a lower risk of coronary disease among men with use of vitamin E supplements. As compared with men who did not take vitamin E supplements, men who took at least 100 IU per day for at least two years had a multivariate relative risk of MI of 0.78 (95 percent confidence interval, 0.65 to 0.95). The benefits of vitamin E were substantially greater among populations free of CVD-related conditions. Among men without self-reported physician-diagnosed hypercholesterolmia, the RR of MI for vitamin E was 0.74 (95% CI 0.60,0.93). Men with hypercholesterolemia did not show appreciable benefit from vitamin E (RR=0.93;95% CI 0.63, 1.37). Men without hypertension had a lower risk of MI associated with vitamin E use (RR=0.74;95% CI 0.58, 0.94) than men with hypertension (RR=0.88;95% CI0.63, 1.22). Men free of either condition showed a significantly greater benefit from taking vitamin E (RR=0.71; 95% CI 0.54, 0.92) than men with either of these two conditions (RR=0.88; 0.67, 1.17). These data suggest a reduced risk of CHD for long term vitamin E supplement use among an otherwise healthy population and are consistent with the recent null findings from secondary prevention trials.

Postmenopausal hormone therapy and mortality.

Postmenopausal hormone therapy has both benefits and hazards, including decreased risks of osteoporosis and cardiovascular disease and an increased risk of breast cancer. We examined the relation between the use of postmenopausal hormones and mortality among participants in the Nurses' Health Study, who were 30 to 55 years of age at base line in 1976. Data were collected by biennial questionnaires beginning in 1976 and continuing through 1992. We documented 3637 deaths from 1976 to 1994. Each participant who died was matched with 10 controls alive at the time of her death. For each death, we defined the subject's hormone status according to the last biennial questionnaire before her death or before the diagnosis of the fatal disease; this reduced bias caused by the discontinuation of hormone use between the time of diagnosis of a potentially fatal disease and death. After adjustment for confounding variables, current hormone users had a lower risk of death (relative risk, 0.63; 95 percent confidence interval, 0.56 to 0.70) than subjects who had never taken hormones; however, the apparent benefit decreased with long-term use (relative risk, 0.80; 0.67 to 0.96, after 10 or more years) because of an increase in mortality from breast cancer among long-term hormone users. Current hormone users with coronary risk factors (69 percent of the women) had the largest reduction in mortality (relative risk, 0.51; 95 percent confidence interval, 0.45 to 0.57), with substantially less benefit for those at low risk (13 percent of the women; relative risk, 0.89; 95 percent confidence interval, 0.62 to 1.28). On average, mortality among women who use postmenopausal hormones is lower than among nonusers; however, the survival benefit diminishes with longer duration of use and is lower for women at low risk for coronary disease.

Vitamin E consumption and the risk of coronary heart disease in men.

The oxidative modification of low-density lipoproteins increases their incorporation into the arterial intima, an essential step in atherogenesis. Although dietary antioxidants, such as vitamin C, carotene, and vitamin E, have been hypothesized to prevent coronary heart disease, prospective epidemiologic data are sparse. In 1986, 39,910 U.S. male health professionals 40 to 75 years of age who were free of diagnosed coronary heart disease, diabetes, and hypercholesterolemia completed detailed dietary questionnaires that assessed their usual intake of vitamin C, carotene, and vitamin E in addition to other nutrients. During four years of follow-up, we documented 667 cases of coronary disease. After controlling for age and several coronary risk factors, we observed a lower risk of coronary disease among men with higher intakes of vitamin E (P for trend = 0.003). For men consuming more than 60 IU per day of vitamin E, the multivariate relative risk was 0.64 (95 percent confidence interval, 0.49 to 0.83) as compared with those consuming less than 7.5 IU per day. As compared with men who did not take vitamin E supplements, men who took at least 100 IU per day for at least two years had a multivariate relative risk of coronary disease of 0.63 (95 percent confidence interval, 0.47 to 0.84). Carotene intake was not associated with a lower risk of coronary disease among those who had never smoked, but it was inversely associated with the risk among current smokers (relative risk, 0.30; 95 percent confidence interval, 0.11 to 0.82) and former smokers (relative risk, 0.60; 95 percent confidence interval, 0.38 to 0.94). In contrast, a high intake of vitamin C was not associated with a lower risk of coronary disease. These data do not prove a causal relation, but they provide evidence of an association between a high intake of vitamin E and a lower risk of coronary heart disease in men. Public policy recommendations with regard to the use of vitamin E supplements should await the results of additional studies.

Prevalence and determinants of estrogen replacement therapy in elderly women

To better understand which women use estrogen replacement therapy, we examined the prevalence and determinants of estrogen replacement therapy in 9704 non black women, age ≥65 years, who participated in the multicenter prospective Study of Osteoporotic Fractures. Overall, 13.7% of women reported current use of orai estrogen; 10.9% look estrogen alone and 2.8% took estrogen opposed by progestin. Four percent currently used parenteral estrogen compounds. Current use declined sharply with age from 17% at age 65 to 4% at age ≥85. The primary determinant of estrogen replacement therapy was the type of menopause; the odds of using estrogen replacement therapy in current users compared with never users were approximately five times higher in women with a surgical menopause. Estrogen use was more common among women who had higher levels of education and were less obese. Furthermore, estrogen replacement therapy users were more likely to drink alcohol and to participate in sports and recreation. A diagnosis of osteoporosis waS the major determinant of continued estrogen use, but only 24% of women with a diagnosis of osteoporosis used estrogen replacement therapy. We conclude that only a small proportion of elderly women in the United States use estrogen replacement therapy. Selection factors for use of estrogen are evident and may introduce bias in studies of estrogen and disease. In consideration of the distribution of these selection factors, estrogen users will tend to be at lower risk of coronary disease and possibly breast cancer but at greater risk for hip fractures.

Prevalence and determinants of estrogen replacement therapy in elderly women

To better understand which women use estrogen replacement therapy, we examined the prevalence and determinants of estrogen replacement therapy in 9704 nonblack women, age greater than or equal to 65 years, who participated in the multicenter prospective Study of Osteoporotic Fractures. Overall, 13.7% of women reported current use of oral estrogen; 10.9% took estrogen alone and 2.8% took estrogen opposed by progestin. Four percent currently used parenteral estrogen compounds. Current use declined sharply with age from 17% at age 65 to 4% at age greater than or equal to 85. The primary determinant of estrogen replacement therapy was the type of menopause; the odds of using estrogen replacement therapy in current users compared with never users were approximately five times higher in women with a surgical menopause. Estrogen use was more common among women who had higher levels of education and were less obese. Furthermore, estrogen replacement therapy users were more likely to drink alcohol and to participate in sports and recreation. A diagnosis of osteoporosis was the major determinant of continued estrogen use, but only 24% of women with a diagnosis of osteoporosis used estrogen replacement therapy. We conclude that only a small proportion of elderly women in the United States use estrogen replacement therapy. Selection factors for use of estrogen are evident and may introduce bias in studies of estrogen and disease. In consideration of the distribution of these selection factors, estrogen users will tend to be at lower risk of coronary disease and possibly breast cancer but at greater risk for hip fractures.

Exercise and heart disease: Epidemiology of the “exercise hypothesis”

The “exercise hypothesis” states that exercise protects against coronary heart disease. Reviewed herein is the epidemiologic evidence for and against the “exercise hypothesis.” The weight of evidence supports the view that exercisers have a lower risk of coronary disease, but that vigorous exercise cannot always prevent progression of coronary atherosclerosis and does increase the risk of sudden death in persons with advanced coronary atherosclerosis. It is concluded that the “exercise hypothesis” is plausible, even likely, but still unproved.

A Study of the Implicit Criteria Used in Diagnosing Chest Pain

Although previous studies have reported the prevalence of coronary artery disease among patients with typical and atypical angina, criteria for the definition of these chest pain syndromes have not been well described. We studied the implicit criteria used by physicians to classify patients with chest pain. Five internists reviewed the histories of 190 subjects admitted to the hospital for elective coronary arteriography and rated each history as indicating either high or low risk of coronary disease. We applied logistic discriminant analysis to these ratings to create a decision rule for the classification of patients with anginal syndromes. The prevalence of confirmed coronary artery disease in subjects classified by the rule as at high risk was 0.83; the prevalence was 0.57 in subjects classified as at low risk. These prevalences are similar to those found for typical and atypical angina in previous large studies. We conclude that this linear model represents the physicians' decisions and provides criteria for defining anginal pain syndromes in certain settings.