Treatment Of Traditional Risk Factors Research Articles

Haptoglobin genotype is a risk factor for coronary artery disease in prediabetes: A case-control study

ObjectiveCoronary artery disease (CAD) prediction remains inconsistent with many unappreciated risk factors. Haptoglobin genotype determines the haptoglobin protein's effectiveness to bind free hemoglobin and prevent oxidative stress, a contributor to atherosclerosis. The haptoglobin 2-2 genotype increases the prevalence of cardiovascular disease (CVD) approximately five times compared to the 1-1 genotype in individuals with diabetes. The risk is unknown in prediabetes. The purpose of this study was to determine an association between haptoglobin genotype and CAD in prediabetes. MethodsThe researchers used case-control convenience sampling from two cardiovascular disease prevention clinics in Memphis, TN, and Spokane, WA, from January 1, 2016 to March 31, 2020. Participants were ages 35–70, had prediabetes, and free of chronic inflammatory or infectious diseases. Cases had a history of subclinical or clinical CAD, while controls did not have a history of CAD. Differences between cases and controls and among haptoglobin genotypes were analyzed using t-tests and ANOVA for continuous variables and chi-square or Fisher's exact tests for categorical variables. Associations among Hp genotypes and CAD were estimated using logistic regression. ResultsThe sample (N = 178; 72 cases and 106 controls) was 96 % white and 64 % male. Cases had lower total cholesterol (p = 0.0001) and high-sensitivity C-reactive protein (p = 0.021). Except for CAD, haptoglobin genotype was independent of any demographic or clinical variable. Haptoglobin 2-2 genotype had 4.0 times higher odds of CAD than haptoglobin 1-1 (p = 0.01). ConclusionHaptoglobin 2-2 genotype had approximately four times higher odds of having CAD compared to the haptoglobin 1-1 genotype. Cases had more desirable clinical profiles, likely attributable to more aggressive treatment of traditional risk factors than controls. Haptoglobin genotype is a potentially important CAD risk factor in prediabetes (88 million Americans). Further studies are needed for interventions to reduce the oxidative stress associated with the Hp 2-2 genotype and glycosylated hemoglobin and for CAD reduction.

Cerebrovascular Disease, Cardiovascular Disease, and Chronic Kidney Disease: Interplays and Influences.

We reviewed reasons for the high cardiovascular risk (CVD) of patients with chronic kidney disease (CKD), and explored alternatives to treatment of traditional risk factors to reduce CVD in CKD. Besides traditional risk factors, patients with CKD are exposed to uremic toxins of two kinds: systemically derived toxins include asymmetric dimethylarginine (ADMA), total homocysteine (tHcy), thiocyanate, tumor necrosis factor alpha, and interleukin 6. Gut-derived uremic toxins (GDUT), products of the intestinal microbiome, include hippuric acid, indoxyl sulfate, p-cresyl sulfate, p-cresyl glucuronide, phenylacetylglutamine, and trimethylamine N-oxide (TMAO). Cyanocobalamin is toxic in patients with CKD. Approaches to reducing plasma levels of these uremic toxins would include diet to reduce GDUT, kidney transplantation, more intensive dialysis, and vitamin therapy to lower tHcy with methylcobalamin rather than cyanocobalamin. The high CVD risk in CKD requires consideration of therapies beyond treatment of traditional risk factors.

Etiology of Persistent Microalbuminuria in Nigeria (P_MICRO study): protocol and study design

BackgroundMicroalbuminuria is an independent risk factor for cardiovascular and kidney disease and a predictor of end organ damage, both in the general population and in persons with HIV (PWH). Microalbuminuria is also an important risk factor for mortality in PWH treated with antiretroviral therapy (ART). In the ongoing Renal Risk Reduction (R3) study in Nigeria, we identified a high prevalence of microalbuminuria confirmed by two measurements 4–8 weeks apart in ART-experienced, virologically suppressed PWH. Although Stage 1 or 2 hypertension and exposure to potentially nephrotoxic antiretroviral medications were common in R3 participants, other traditional risk factors for albuminuria and kidney disease, including diabetes, APOL1 high-risk genotype, and smoking were rare. Co-infection with endemic pathogens may also be significant contributors to albuminuria, but co-infections were not evaluated in the R3 study population.MethodsIn Aim 1, we will cross-sectionally compare the prevalence of albuminuria and established kidney disease risk factors in a cohort of PWH to age- and sex-matched HIV-negative adults presenting for routine care at the Aminu Kano Teaching Hospital in Kano, Nigeria. We will leverage stored specimens from 2500 R3 participants and enroll an additional 500 PLWH recently initiated on ART (≤ 24 months) and 750 age- and sex-matched HIV-negative adults to determine the contribution of HIV, hypertension, and other comorbid medical conditions to prevalent albuminuria. In Aim 2, we will follow a cohort of 1000 HIV-positive, ART-treated and 500 HIV-negative normoalbuminuric adults for 30 months to evaluate the incidence and predictors of albuminuria.DiscussionThe findings from this study will support the development of interventions to prevent or address microalbuminuria in PWH to reduce kidney and cardiovascular morbidity and mortality. Such interventions might include more intensive monitoring and treatment of traditional risk factors, the provision of renin-angiotensin aldosterone system or sodium-glucose cotransporter-2 inhibitors, consideration of changes in ART regimen, and screening and treatment for relevant co-infections.

Recommendations from the EGAPP Working Group: Genomic profiling to assess cardiovascular risk to improve cardiovascular health

Summary of RecommendationsThe Evaluation of Genomic Applications in Practice and Prevention Working Group (EWG) found insufficient evidence to recommend testing for the 9p21 genetic variant or 57 other variants in 28 genes (listed in Table 1) to assess risk for cardiovascular disease (CVD) in the general population, specifically heart disease and stroke. The EWG found that the magnitude of net health benefit from use of any of these tests alone or in combination is negligible. The EWG discourages clinical use unless further evidence supports improved clinical outcomes. Based on the available evidence, the overall certainty of net health benefit is deemed “Low.” RationaleIt has been suggested that an improvement in CVD risk classification (adjusting intermediate risk of CVD into high- or low-risk categories) might lead to management changes (e.g., earlier initiation or higher rates of medical interventions, or targeted recommendations for behavioral change) that improve CVD outcomes. In the absence of direct evidence to support this possibility, this review sought indirect evidence aimed at documenting the extent to which genomic profiling alters CVD risk estimation, alone and in combination with traditional risk factors, and the extent to which risk reclassification improves health outcomes. Analytic validityAssay-related evidence on available genomic profiling tests was deemed inadequate. However, based on existing technologies that have been or may be used and on data from two of the companies performing such testing, the analytic sensitivity and specificity of tests for individual gene variants might be at least satisfactory. Clinical validityTwenty-nine gene candidates were evaluated, with 58 different gene variant/disease associations. Evidence on clinical validity was rated inadequate for 34 of these associations (59%) and adequate for 23 (40%). Inadequate grades were based on limited evidence, poor replication, existence of possible biases, or combinations of these factors. For heart disease (25 combined associations) and stroke (13 combined associations), profiling provided areas under the receiver operator characteristics curve of 66% and 57%, respectively. Only the association of 9p21 variants with heart disease had convincing evidence of a per-allele odds ratio of between 1.2 and 1.3; this was the highest effect size for any variant/disease combination with at least adequate evidence. Although the 9p21 association seems to be independent of traditional risk factors, there is adequate evidence that the improvement in risk prediction is, at best, small. Clinical utilityClinical utility was not formally evaluated in any of the studies reported to date, including for 9p21. As a result, no evidence was available on the balance of benefits and harms. Also, there was no direct evidence available to assess the health benefits and harms of adding these markers to traditional risk factors (e.g., Framingham Risk Score). However, the estimated additional benefit from adding genomic markers to traditional risk factors was found to be negligible. Contextual IssuesPrevention of CVD is a public health priority. Improvements in outcomes associated with genomic profiling could have important impacts. Traditional risk factors such as those used in the Framingham Risk Scores have an advantage in clinical screening and risk assessment strategies because they measure the actual targets for therapy (e.g., lipid levels and blood pressure). To add value, genomic testing should lead to better outcomes than those achievable by assessment and treatment of traditional risk factors alone. Some issues important for clinical utility remain unknown, such as the biological mechanism underlying the most convincing marker's (9p21) association with CVD; the level of risk that changes intervention; whether long-term disease outcomes will improve; how individuals ordering direct to consumer tests will understand/respond to test results and interact with the health care system; and whether direct to consumer testing will motivate behavior change or amplify potential harms.

Inflammatory bowel disease and cardiovascular diseases: a concise review.

Cardiovascular diseases (CVDs) remain the leading cause of morbidity and mortality despite aggressive treatment of traditional risk factors. Chronic inflammation plays an important role in the initiation and progression of CVDs. Inflammatory bowel disease (IBD) is a systemic state of inflammation exhibiting increased levels of pro-inflammatory cytokines including tumour necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6. Importantly, IBD is associated with increased risk for CVDs especially in women and young adults, including coronary artery disease, stroke, thromboembolic diseases, and arrhythmias. Potential mechanisms underlying the increased risk for CVDs in IBD patients include increased levels of inflammatory cytokines and oxidative stress, altered platelet function, hypercoagulability, decreased numbers of circulating endothelial progenitor cells, endothelial dysfunction, and possible interruption of gut microbiota. Although IBD does not appear to exacerbate the traditional risk factors for CVDs, including hypertension, hyperlipidaemia, diabetes mellitus, and obesity, aggressive risk stratifications are important for primary and secondary prevention of CVDs for IBD patients. Compared to 5-aminosalicylates and corticosteroids, anti-TNF-α therapy in IBD patients was consistently associated with decreasing cardiovascular events. In the absence of contraindications, low-dose aspirin and statins appear to be beneficial for IBD patients. Low-molecular-weight heparin is also recommended for patients who are hospitalized with acute IBD flares without major bleeding risk. A multidisciplinary team approach should be considered for the management of IBD patients.

Metabolic Activation of Flavin Monooxygenase-mediated Trimethylamine-N-Oxide Formation in Experimental Kidney Disease

Cardiovascular disease (CVD) remains the leading cause of death in chronic kidney disease (CKD) patients despite treatment of traditional risk factors, suggesting that non-traditional CVD risk factors are involved. Trimethylamine-N-oxide (TMAO) correlates with atherosclerosis burden in CKD patients and may be a non-traditional CVD risk factor. Serum TMAO concentrations are significantly increased in CKD patients, which may be due in part to increased hepatic flavin monooxygenase (FMO)-mediated TMAO formation. The objective of this work was to elucidate the mechanism of increased FMO activity in CKD. In this study, FMO enzyme activity experiments were conducted in vitro with liver microsomes isolated from experimental CKD and control rats. Trimethylamine was used as a probe substrate to assess FMO activity. The FMO activator octylamine and human uremic serum were evaluated. FMO gene and protein expression were also determined. FMO-mediated TMAO formation was increased in CKD versus control. Although gene and protein expression of FMO were not changed, metabolic activation elicited by octylamine and human uremic serum increased FMO-mediated TMAO formation. The findings suggest that metabolic activation of FMO-mediated TMAO formation is a novel mechanism that contributes to increased TMAO formation in CKD and represents a therapeutic target to reduce TMAO exposure and CVD.

Biobanking for discovery of novel cardiovascular biomarkers using imaging-quantified disease burden: protocol for the longitudinal, prospective, BioHEART-CT cohort study

IntroductionCoronary artery disease (CAD) persists as a major cause of morbidity and mortality worldwide despite intensive identification and treatment of traditional risk factors. Data emerging over the past decade show...

Early Detection System of Vascular Disease and Its Application Prospect.

Markers of imaging, structure, and function reflecting vascular damage, integrating a long time accumulation effect of traditional and unrecognized cardiovascular risk factors, can be regarded as surrogate endpoints of target organ damage before the occurrence of clinical events. Prevention of cardiovascular disease requires risk stratification and treatment of traditional risk factors, such as smoking, hypertension, hyperlipidemia, and diabetes. However, traditional risk stratification is not sufficient to provide accurate assessment of future cardiovascular events. Therefore, vascular injury related parameters obtained by ultrasound or other noninvasive devices, as a surrogate parameter of subclinical cardiovascular disease, can improve cardiovascular risk assessment and optimize the preventive treatment strategy. Thus, we will summarize the research progress and clinical application of early assessment technology of vascular diseases in the present review.

Abstract T P392: Optimal Combination Secondary Prevention Drug Treatment and Stroke Outcomes

Background: Over the last decade there has been a documented decline in the stroke incidence and mortality in several developed nations around the world, which is thought to be due mainly to better treatment of traditional risk factors for stroke. It has been suggested that optimal combination(s) of individually proven secondary prevention drug classes, could reduce recurrent vascular events. However, the effect of combining antihypertensive agents (AH), lipid modifiers (LM), and antithrombotic agents (AT) on outcomes after stroke has not previously been studied. Methods: We analyzed the database of a multicenter trial involving 3680 recent ischemic stroke patients aged ≥35 years and followed for 2 years. Patients were categorized by appropriateness level 0 to III depending on the number of the drugs prescribed divided by the number of the drugs potentially indicated for each patient (0=none of the indicated medications prescribed and III=all indicated medications prescribed). Independent associations of medication appropriateness level with recurrent stroke (primary outcome), stroke/coronary heart disease (CHD)/vascular death (secondary outcome), and all-cause death (tertiary outcome) were assessed. Results: The unadjusted rate of stroke declined with increasing medication appropriateness level (15.9% for level 0; 10.3% for level I; 8.6% for level II; and 7.3% for level III). Compared to level 0: the adjusted hazard ratio (AHR) of stroke for level I was (0.51, 95% CI, 0.21–1.25), level II 0.50 (0.23–1.09), and level III 0.39 (0.18–0.84); of stroke/CHD/vascular death for level I 0.60 (0.32-1.14), level II 0.45 (0.25–0.80), and level III 0.39 (0.22–0.69); of all-cause death for level I 0.89 (0.30-2.64), level II 0.71 (0.26-1.93), and level III 0.35 (0.13–0.96). Interpretation: Optimal combination prescription of secondary prevention medication was associated with an independent lower risk of stroke, stroke/CHD/vascular death, and all-cause death in recent stroke patients over a 2 year follow-up period. While future studies are certainly warranted to confirm/disconfirm our findings, clinicians may want to ensure that for eligible recent stroke patients, all appropriate secondary prevention drug classes are prescribed and maintained.

Abstract P335: The Number of Coronary Arteries with Calcified Plaque is Increased in Type 1 Diabetes

Adults with type 1 diabetes (T1D) have a higher risk for cardiovascular disease than non-diabetic (non-DM) adults. Coronary artery calcification (CAC) is a marker for subclinical atherosclerosis and the Agatston CAC score is the standard used today. The aim of our study was to look at the number of coronary arteries with calcified plaques to determine if more diffuse disease is present in adults with T1D for a given level of CAC. In addition, we examined risk factors associated with the number of coronary arteries with CAC, as this could be a novel way to risk-stratify individuals. This study consisted of 1169 participants (T1D n=535 and non-DM n =634) with a mean ± SD age of 39±9 years. CAC was measured by electron beam CT (EBCT) using two scans performed five minutes apart and the maximum number of coronary arteries with CAC was used in the analysis. CAC lesions were determined in the left main, left anterior descending, circumflex, and right coronary arteries, with a maximum number of arteries with CAC ranging from zero to four. Chi square analysis was used to compare the number of coronary arteries with CAC by diabetes group. Subjects were then divided into categories based on their CAC score (>0-10, 10-100, >100-300, >300) and poisson regression was used in multivariable analysis to examine associated risk factors. Adults with T1D had a significantly higher number of coronary arteries with CAC lesions than the non-DM adults (p > 0.0001). Among subjects with CAC>300 (n=58), adults with T1D had more coronary arteries with CAC than the controls (p = 0.03), but there were no differences in number of arteries with CAC among the other Agatston score categories. In multivariable analysis, HDL and LDL cholesterol, BMI, and hypertension were all independently associated with the number of coronary arteries with CAC lesions when adjusting for age, diabetes and CAC score (p<0.0001). There were no significant associations of number of arteries with CAC with smoking status or hemoglobin A1c. People with T1D were still significantly more likely to have more coronary arteries with CAC lesions than non-DM individuals after adjusting for the above factors. In conclusion, T1D patients have more diffuse subclinical atherosclerosis, as indicated by a greater number of coronary arteries with CAC compared with non-DM adults. The number of coronary arteries with calcified plaque was independently associated with traditional CVD risk factors, even when accounting for CAC score. These findings are important because traditionally just the Agatston CAC score is used to determine CVD risk, but the number of coronary arteries affected could indicate how diffuse the subclinical artherosclerosis is prompt for aggressive treatment of traditional risk factors.

Venous and Arterial Thrombosis Associated with HIV Infection

The advent of highly active antiretroviral therapy (HAART) and the appropriate use of prophylactic strategies to prevent opportunistic infections have drastically decreased human immunodeficiency virus (HIV) infection-related mortality. However, there is growing evidence that metabolic abnormalities associated with HIV infection and with its treatment may lead to an increased risk of cardiovascular (CV) events. Several studies showed an increased risk of symptomatic and subclinical CV events in these patients. On the other hand, the association with venous thromboembolic events is less compelling. This increased risk is possibly explained by the coexistence in this population of different risk factors determined by the HIV infection per se, by the higher prevalence of traditional CV risk factors such as obesity, smoking, hypertension, hyperlipidemia, and glucose intolerance, as compared with the general population, and by the effects of HAART. Thus, systematic identification and aggressive treatment of traditional risk factors seem to be necessary to prevent the development of cardiovascular disease in this population.

Screening asymptomatic patients with diabetes for unknown coronary artery disease: does it reduce risk? An open-label randomized trial comparing a strategy based on exercise testing aimed at revascularization with management based on pharmacological/behavioural treatment of traditional risk factors. DADDY-D Trial (Does coronary Atherosclerosis Deserve to be Diagnosed and treated early in Diabetics?).

BackgroundCoronary artery disease is the leading cause of morbidity and mortality in patients with type 2 diabetes. Screening for asymptomatic coronary artery disease with treatment by means of revascularization seems to be an appealing option for prevention. The utility of such a strategy has never been challenged in a randomized trial.Methods/DesignIn the present study a cohort of diabetic patients without any symptoms and without known coronary artery disease will be screened at two diabetes outpatients services. Those with intermediate or high risk (equal or greater than 10% according to the Italian risk chart) will be asked to participate and enrolled. They will be seen and followed in order to provide the best adherence to medical therapy. Half of the patients will be randomized to undergo an exercise tolerance testing while the other group will continue to be regularly seen at diabetes outpatients services. Best medical/behavioral therapy will be offered to both groups. Those patients with a positive exercise tolerance testing will be studied by coronary angiography and treated according to the severity of coronary lesions by percutaneous stenting or surgery.The objective of the study is to evaluate the efficacy of the screening strategy aimed at revascularization. A cost-effectiveness analysis will be performed at the end of the follow up.DiscussionThe study will provide useful information about prevention and treatment of diabetic patients at high risk of coronary events. It will be made clearer if detection of silent coronary artery disease has to be recommended and followed by treatment. Given the simplicity of the study protocol, it will be easily transferable to the real world.Trial registration(ClinicalTrials.gov): NCT00547872

The Emergent Cardiovascular Risk Factors and Organ Damage in Arterial Hypertension

Correction of cardiovascular risk factors is a mainstay of the treatment of hypertensive patients that have developed or might develop target organ damage. In addition to traditional risk factors, such as smoking, diabetes, obesity, and dyslipidemia, clinical research has identified additional conditions that put patients at a greater risk of developing cardiovascular disease and that might achieve particular relevance in the hypertensive state. Over the last decades, effective intervention in the treatment of traditional risk factors has reduced remarkably cardiovascular morbidity and mortality, but the incidence of coronary artery disease, stroke, and renal failure remains unacceptably high. Emerging cardiovascular risk factors are likely to contribute substantially to this picture and it could be anticipated that their contribution will become increasingly evident in the future. Physicians involved in the field of hypertension and dealing with problems concerning cardiovascular prevention should be aware of these new risk factors, give them an appropriate consideration, and correct them whenever possible. This review will consider the literature supporting the role of lipoprotein(a), homocysteine, and fibrinogen as contributors to cardiovascular risk in the general population and, more specifically, to the development and progression of target organ damage in hypertensive patients. The impact of early impairment of renal function on these factors will be analyzed in relation to the progression of renal disease as found in patients with hypertensive nephrosclerosis.

Prevalence and treatment of cardiovascular disease and traditional risk factors in Australian adults with renal insufficiency

To evaluate the prevalence and treatment of cardiovascular disease and traditional cardiovascular disease risk factors in Australian adults with renal insufficiency. The Australian Diabetes, Obesity and Lifestyle Study was a cross-sectional survey of Australian adults undertaken in 1999-2000. Participants were categorized based on the Cockcroft-Gault estimated glomerular filtration rate in terms of normal renal function (<60 mL/min per 1.73 m(2)) and renal insufficiency (<60 mL/min per 1.73 m(2)). Outcome measures were the prevalence of cardiovascular disease, estimated risk of cardiovascular disease (20% over 10 years) and traditional cardiovascular risk factors, and frequency of pharmacological treatment of traditional cardiovascular risk factors. Among adults with renal insufficiency, cardiovascular disease was present in 29.4 (95% CI: 25.1-33.6) per 100, with an additional 47.9 (95% CI: 44.9-50.9) per 100 having an estimated risk of cardiovascular disease (20% over 10 years). At least one cardiovascular risk factor was present in 90.1%. Hypertension and type 2 diabetes mellitus were three times more frequent, while hyperlipidaemia was nearly twice as frequent in those participants with renal insufficiency. Of those with renal insufficiency, 58.2% with hypertension were treated, with only 14.5% of this group being treated to current recommended target levels of blood pressure, while only 32.5% with hyperlipidaemia were treated, with 7.4% of this group being treated to target lipid levels. The present study demonstrates significant scope to reduce the high burden of cardiovascular risk factors in Australian adults with renal insufficiency in the general community, through treatment of traditional risk factors for cardiovascular disease.

Hemodialysis-associated hypertension: pathophysiology and therapy.

The majority of end-stage renal disease (ESRD) patients are hypertensive. Hypertension in the hemodialysis patient population is multifactorial. Further, hypertension is associated with an increased risk for left ventricular hypertrophy, coronary artery disease, congestive heart failure, cerebrovascular complications, and mortality. Antihypertensive medications alone do not adequately control blood pressure (BP) in hemodialysis patients. There are, however, several therapeutic options available to normalize BP in these patients, often without the need for additional drug therapy (eg, long, slow hemodialysis; short, daily hemodialysis; nocturnal hemodialysis; or, most effectively, dietary salt and fluid restriction in combination with reduction of dialysate sodium concentration). Optimal BP in dialysis patients is not different from recommendations for the general population, even though definite evidence is not yet available. Predialysis systolic and diastolic BPs are of particular importance. Left ventricular mass correlates with predialysis systolic BP. Survival is better in hemodialysis patients with a mean arterial pressure below 99 mm Hg as compared with those with higher BP. Low predialysis systolic BP (<110 mm Hg) and low predialysis diastolic BP (<70 mm Hg) are associated with increased mortality, primarily because of severe congestive heart failure or coronary artery disease. Patients that experience repeated intradialytic hypotensive episodes should also be viewed with caution, and predialytic BP values should be reevaluated. A possible treatment option for these patients may be slow, long hemodialysis; short, daily hemodialysis; or nocturnal hemodialysis. Among the antihypertensive agents currently available, angiotensin-converting enzyme (ACE) inhibitors appear to have the greatest ability to reduce left ventricular mass. Pressure load can be satisfactorily determined by using the average value of predialysis BP measurements over 1 month. In selected hemodialysis patients, interdialytic ambulatory blood pressure monitoring (ABPM) may help to determine if the patient is in fact hypertensive. In addition, ABPM provides important information about the change in BP between day and night. Regular home BP monitoring, yearly echocardiography, and treatment of traditional risk factors for cardiovascular disease are recommended.

Psychosocial Stress and Cardiovascular Disease: Pathophysiological Links

The remarkable decline in cardiovascular disease (CVD) experienced in developed countries over the last 40 years appears to have abated. Currently, many CVD patients continue to show cardiac events despite optimal treatment of traditional risk factors. This evidence suggests that additional interventions, particularly those aimed at nontraditional factors, might be useful for continuing the decline. Psychosocial stress is a newly recognized (nontraditional) risk factor that appears to contribute to all recognized mechanisms underlying cardiac events, specifically, (a) clustering of traditional cardiovascular risk factors, (b) endothelial dysfunction, (c) myocardial ischemia, (d) plaque rupture, (e) thrombosis, and (f) malignant arrhythmias. A better understanding of the behavioral and physiologic associations between psychosocial stress and CVD will assist researchers in identifying effective approaches for reducing or reversing the damaging effects of stress and may lead to further reductions of CVD morbidity and mortality.