Impact on percutaneous coronary intervention for acute coronary syndromes during the COVID-19 outbreak in a non-overwhelmed European healthcare system: COVID-19 ACS-PCI experience in Ireland.

AIMS: To evaluate temporal trends of acute coronary syndromes (ACS) treated via percutaneous coronary intervention (PCI) throughout the COVID-19 outbreak in a European healthcare system affected but not overwhelmed by COVID-19-related pathology. METHODS AND RESULTS: We performed a retrospective multicentre analysis of the rates of PCI for the treatment of ACS within the period 2 months pre and post the first confirmed COVID-19 case in Ireland, as well as comparing PCI for ST-elevation myocardial infarction (STEMI) with the corresponding period in 2019. During the 2020 COVID-19 period (29 February-30 April 2020), there was a 24% decline in PCI for overall ACS (incidence rate ratio (IRR) 0.76; 95% CI 0.65 to 0.88; p<0.001), including a 29% reduction in PCI for non-ST-elevation ACS (IRR 0.71; 95% CI 0.57 to 0.88; p=0.002) and an 18% reduction in PCI for STEMI (IRR 0.82; 95% CI 0.67 to 1.01; p=0.061), as compared with the 2020 pre-COVID-19 period (1 January-28 February 2020). A 22% (IRR 0.78; 95% CI 0.65 to 0.93; p=0.005) reduction of PCI for STEMI was seen as compared with the 2019 reference period. CONCLUSION: This study demonstrates a significant reduction in PCI procedures for the treatment of ACS since the COVID-19 outbreak in Ireland. The reasons for this decline are still unclear but patients need to be encouraged to seek medical attention when cardiac symptoms appear, in order to avoid incremental cardiac morbidity and mortality due to a reduction in coronary revascularisation for the treatment of ACS.

MiR-93-5p is a novel predictor of coronary in-stent restenosis.

AIMS: MicroRNAs (miRNAs), small non-coding RNAs, have been implicated as regulators of multiple phases of atherothrombosis, and some reports have suggested altered levels in coronary artery in-stent restenosis (ISR). We recently demonstrated that miR-93-5 p was able to discriminate between patients with stable coronary artery disease (CAD) and those with no CAD, after adjusting for traditional risk factors (RFs). Thus, we wanted to determine if circulating miRNAs could predict coronary ISR. OBJECTIVE: To determine if circulating miRNAs have diagnostic capability for determining ISR in a cohort of matched patients with and without ISR. APPROACH AND RESULTS: To determine if miRNA plasma levels are elevated in coronary ISR, we conducted a study comprising 78 patients (39 with no ISR and 39 with ISR) and measured plasma miRNAs in each. We then determined the predictive ability of differential miRNAs, adjusting for Framingham Heart Study (FHS) RFs, and stent length and diameter, to discriminate between ISR and no ISR. After correction for multiple testing, two miRNAs-miR425-5p and miR-93-5 p-were differential between patients with ISR and patients without ISR. Only miR-93-5 p remained a strong independent predictor of ISR after correction for FHS RFs (OR 6.30, p=0.008) and FHS RFs plus stent length and diameter (OR 4.80, p=0.02) and improved discriminatory power for ISR over FHS RFs alone in receiver operator characteristic curve analysis. CONCLUSION: This novel finding that miR-93-5 p independently predicts ISR extends our recent observation that miR-93-5 p predicted CAD after adjustment for traditional CAD RFs. These data suggest further potential diagnostic utility.

Influence of race on death and ischemic complications in patients with non-ST-elevation acute coronary syndromes despite modern, protocol-guided treatment.

BACKGROUND: In the setting of acute coronary syndromes (ACS), nonwhite patients are less likely to undergo invasive cardiac procedures and may have worse clinical outcomes than white patients. Whether the disparate outcomes exist independently of potential biases in treatment patterns remains unclear. METHODS AND RESULTS: We examined the association between race and outcome in the Treat Angina with Aggrastat and Determine Cost of Therapy With an Invasive or Conservative Strategy-Thrombolysis in Myocardial Infarction 18 study (TACTICS-TIMI 18), a randomized trial of invasive versus conservative treatment strategy in patients with non-ST-elevation ACS. There were 1722 white and 461 nonwhite patients. After adjustment for differences in medical characteristics, nonwhite patients were at significantly increased risk for death, MI, or rehospitalization for ACS (hazard ratio [HR], 1.54; P=0.003). Rates of protocol-guided angiography and revascularization were similar in both groups. For non-protocol-guided care, however, we found significant disparities, with nonwhite patients less likely to be taking their cardiac medications at follow-up (odds ratio [OR], 0.59; P=0.0002), to undergo non-protocol-mandated angiography (OR, 0.40; P=0.03), to receive a stent if undergoing percutaneous coronary intervention (OR, 0.55; P=0.045), and to have less procedural success after percutaneous coronary intervention (acute gain, 1.40+/-0.83 versus 1.81+/-0.92 mm; P=0.004). Nonetheless, an invasive strategy was similarly efficacious in white (HR, 0.66; 95% CI, 0.50 to 0.88) and nonwhite (HR, 0.85; 95% CI, 0.52 to 1.39) patients (P(interaction)=0.52), especially in those with troponin elevation or ST deviation. CONCLUSIONS: After adjustment for baseline characteristics, nonwhite patients had a significantly worse prognosis than white patients, regardless of treatment approach. In the absence of protocol guidance, important disparities emerged between the care given the 2 groups. An early invasive strategy is beneficial in and should be considered for all patients, regardless of race.

miRNA-93-5p and other miRNAs as predictors of coronary artery disease and STEMI.

BACKGROUND: MicroRNAs (miRNAs), small non-coding RNAs, have been implicated as regulators of all mediators of atherosclerosis, and some reports have suggested increased levels in coronary artery disease (CAD) and acute myocardial infarction (AMI). However, the potential of miRNAs as biomarkers or predictors of disease remains to be established. METHODS: We designed a study comprising 150 patients (50 Control, 50 Stable CAD, and 50 ST Elevation Myocardial Infarction (STEMI)), and measured plasma miRNAs in each. We then determined the ability of differential miRNAs, adjusting for Framingham Heart Study (FHS) risk factors, to discriminate between CAD vs Control, and STEMI vs Control. RESULTS: Three miRNAs (miR15a-5p, miR16-5p, and miR93-5p) were significantly increased in Stable CAD vs Control groups and one (miR146a-5p) was significantly decreased in Stable CAD vs Control. One miRNA - miR499a-5p - was significantly increased in the STEMI group compared to Controls. After adjustment for FHS risk factors, miR93-5p levels remained an independent predictor of the presence of CAD (Odds Ratio [OR]=8.76, P=0.002). All 4 miRNAs improved discriminatory power for CAD over FHS alone in ROC analysis. Similarly, after adjustment for risk factors miR499-5p remained an independent predictor of STEMI (OR=3.03, P=0.001) and improved discriminatory power for STEMI in ROC analyses. CONCLUSION: We identified 4 miRNAs that were differentially expressed among stable CAD and control patients, and 1 miRNA that was elevated in STEMI patients vs controls. MiR93-5p was the strongest predictor of CAD after adjustment for traditional risk factors, suggesting potential diagnostic utility.

Low-density lipoprotein particle concentration and size as determined by nuclear magnetic resonance spectroscopy as predictors of cardiovascular disease in women.

BACKGROUND: Nuclear magnetic resonance (NMR) offers an alternative, spectroscopic means of quantifying LDL and of measuring LDL particle size. METHODS AND RESULTS: We conducted a prospective nested case-control study among healthy middle-aged women to assess LDL particle size (NMR) and concentration (NMR) as risk factors for future myocardial infarction, stroke, or death of coronary heart disease. Median baseline levels of LDL particle concentration (NMR) were higher (1597 vs 1404 nmol/L; P= 0.0001) and LDL particle size (NMR) was lower (21.5 vs 21.8 nm; P=0.046) among women who subsequently had cardiovascular events (n=130) than among those who did not (n= 130). Of these 2 factors, LDL particle concentration (NMR) was the stronger predictor (relative risk for the highest compared with the lowest quartile=4.17, 95% CI 1.96-8.87). This compared with a relative risk of 3.11 (95% CI 1.55-6.26) for the ratio of total cholesterol to HDL cholesterol and a relative risk of 5.91 (95% CI 2.65-13.15) for C-reactive protein. The areas under the receiver operating characteristic curves for LDL particle concentration (NMR), total cholesterol to HDL cholesterol ratio, and C-reactive protein were 0.64, 0.64, and 0.66, respectively. LDL particle concentration (NMR) correlated with several traditionally assessed lipid and nonlipid risk factors, and thus adjustment for these tended to attenuate the magnitude of association between LDL particle concentration (NMR) and risk. CONCLUSIONS: In this cohort, LDL particle concentration measured by NMR spectroscopy was a predictor of future cardiovascular risk. However, the magnitude of predictive value of LDL particle concentration (NMR) was not substantively different from that of the total cholesterol to HDL cholesterol ratio and was less than that of C-reactive protein.

Blood pressure, C-reactive protein, and risk of future cardiovascular events.

BACKGROUND: Accumulating data suggest a link between blood pressure and vascular inflammation. METHODS AND RESULTS: We examined the relationship between blood pressure, C-reactive protein (CRP), and incident first cardiovascular events among 15 215 women followed prospectively over a median of 8.1 years. In cross-sectional analyses at baseline, median levels of CRP for women with blood pressure <120/75, 120 to 129/75 to 84, 130 to 139/85 to 89, 140 to 159/90 to 94, and > or =160/95 mm Hg were 0.96, 1.42, 2.20, 2.82, and 3.34 mg/L, respectively (P for trend <0.0001). Increasing categories of blood pressure were significant predictors of CRP levels at baseline. In prospective analyses, both elevated CRP levels (> or =3 mg/L) and increasing categories of blood pressure were independent determinants of future cardiovascular events, and CRP had incremental prognostic value at all levels of blood pressure. The adjusted hazard ratio for women with blood pressure > or =160/95 mm Hg and CRP levels > or =3 mg/L was 8.31 (95% CI, 4.44 to 15.55, P<0.0001) compared with those with blood pressure <120/75 and CRP levels <3 mg/L. After participants had been divided into 4 groups on the basis of CRP levels (<3 or > or =3 mg/L) and blood pressure levels (<130/85 or > or =130/85), the risk factor-adjusted hazard ratios were as follows: low CRP/low blood pressure, 1.0; high CRP/low blood pressure, 1.87 (P=0.002); low CRP/high blood pressure, 2.54 (P<0.0001); and high CRP/high blood pressure, 3.27 (P<0.0001). CONCLUSIONS: CRP and blood pressure are independent determinants of cardiovascular risk, and their predictive value is additive.

C-reactive protein and other inflammatory risk markers in acute coronary syndromes.

Markers of myocyte necrosis such as cardiac troponin or creatine kinase-myocardial band are invaluable tools for risk stratification among patients presenting with acute coronary syndromes (ACS). Nonetheless, many patients without any evidence of myocyte necrosis may be at high risk for recurrent ischemic events. In consideration of the important role that inflammatory processes play in determining plaque stability, recent work has focused on whether plasma markers of inflammation may help improve risk stratification. Of these markers, C-reactive protein (CRP) has been the most widely studied, and there is now robust evidence that CRP is a strong predictor of cardiovascular risk among apparently healthy individuals, patients undergoing elective revascularization procedures, and patients presenting with ACS. Moreover, even among patients with troponin-negative ACS, elevated levels of CRP are predictive of future risk. Other, more upstream markers of the inflammatory cascade, such as interleukin (IL)-6, have also been found to be predictive of recurrent vascular instability. A recent report from the second FRagmin during InStability in Coronary artery disease trial investigators suggests that elevated levels of an inflammatory marker such as IL-6 may indicate which patients may benefit most from an early invasive strategy. Other inflammatory markers currently under investigation include lipoprotein-associated phospholipase A(2), myeloperoxidase, and pregnancy-associated plasma protein A. Of all these novel markers, CRP appears to meet most of the criteria required for potential clinical application. Furthermore, the benefits of lifestyle modification and drug therapy with aspirin or statins may be most marked among those with elevated CRP levels.

Projected life-expectancy gains with statin therapy for individuals with elevated C-reactive protein levels.

OBJECTIVES: We sought to estimate the potential gains in life expectancy achieved with statin therapy for individuals without overt hyperlipidemia but with elevated C-reactive protein (CRP) levels. BACKGROUND: Persons with low-density lipoprotein (LDL) cholesterol levels below current treatment guidelines and elevated CRP levels are at increased risk of cardiovascular disease and may benefit from statin therapy. METHODS: We constructed a decision-analytic model to estimate the gains in life expectancy with statin therapy for individuals without overt hyperlipidemia but with elevated CRP levels. The annual risks of myocardial infarction (MI) and stroke, as well as the efficacy of statin therapy, were based on evidence from randomized trials. Estimates of prognosis after MI or stroke were derived from population-based studies. RESULTS: We estimated that 58-year-old men and women with CRP levels >or=0.16 mg/dl but LDL cholesterol <149 mg/dl would gain 6.6 months and 6.4 months of life expectancy, respectively, with statin therapy. These gains were similar to those for patients with LDL cholesterol >or=149 mg/dl (6.7 months for men and 6.6 months for women). In sensitivity analyses, we identified the baseline risk of MI and the efficacy of statin therapy for preventing MI as the most important factors in determining the magnitude of benefit with statin therapy. CONCLUSIONS: Our results suggest that individuals with elevated CRP levels, many of whom do not meet current National Cholesterol Education Program guidelines for drug treatment, may receive a substantial benefit from statin therapy. This analysis supports a crucial need for direct intervention trials aimed at subjects with elevated CRP levels.

Soluble CD40 ligand levels indicate lipid accumulation in carotid atheroma: an in vivo study with high-resolution MRI.

OBJECTIVE: The CD40/CD40 ligand pathway mediates inflammatory processes important in atherogenesis and the formation of the intraplaque lipid pool. We tested the hypothesis that plasma levels of soluble CD40 ligand are elevated in patients with evidence of a lipid pool on high-resolution magnetic resonance imaging (MRI) of carotid stenoses. METHODS AND RESULTS: We recruited 49 patients with evidence of carotid atherosclerosis on ultrasonography; 3 patients could not undergo carotid MRI because of claustrophobia. The remaining 46 patients underwent high-resolution MRI of the carotid arteries. Two radiologists blinded to all other data determined the presence or absence of an intraplaque lipid pool based on the loss of signal between the 20-ms echo time (TE20) and the fat-suppressed TE55 fast spin-echo images. Plasma levels of soluble CD40 ligand were determined by ELISA. Baseline levels of soluble CD40 ligand were higher among patients with evidence of intraplaque lipid (n=14) than among those without it (n=32; median, 2.54 ng/mL; interquartile range [IQR], 1.85 to 3.52 vs median, 1.58 ng/mL; IQR, 1.21 to 2.39; P=0.02). In contrast, soluble CD40 ligand levels were not correlated with percent diameter stenosis (r=-0.19; P=0.21). The relative risk for intraplaque lipid associated with soluble CD40 ligand levels above the median was 6.0 (95% confidence interval, 1.15 to 31.23; P=0.03). The magnitude of this predictive effect did not substantially change after adjustment for traditional cardiovascular risk factors (relative risk, 5.12; 95% confidence interval, 0.78 to 33.73; P=0.09). CONCLUSIONS: Plasma levels of soluble CD40 ligand may predict patients with features of high-risk atherosclerotic lesions. These data provide novel insight into the mechanism through which elevated levels of soluble CD40 ligand may reflect cardiovascular risk in humans and illustrate the potential value of interfacing high-resolution MRI with studies of vascular inflammation.

Hemoglobin A1c level and future cardiovascular events among women.

BACKGROUND: Available data suggest that hemoglobin A(1c) (A(1c)), also known as glycosylated hemoglobin, levels may be related to cardiovascular risk in the general population without diabetes mellitus. We sought to test this hypothesis prospectively in a cohort of women without overt cardiovascular disease. METHODS: We conducted a nested case-control study of the Women's Health Study cohort. We identified 464 case patients with incident myocardial infarction, stroke, or coronary revascularization and 928 unmatched control subjects who remained free of cardiovascular events at case diagnosis. The mean follow-up was 7 years. RESULTS: Of the overall study population, 136 had a history of diabetes mellitus or an overtly elevated baseline A(1c) level (>6.4%) and were excluded from the primary analyses. Among women without diabetes mellitus or an elevated baseline A(1c) level, mean +/- SD baseline levels of A(1c) were significantly higher among future cases than controls (5.47% +/- 0.27% vs 5.37% +/- 0.22%; P<.001). The crude relative risks (RRs) of incident cardiovascular events for increasing quartiles of A(1c) were 1.00, 0.98, 1.33, and 2.25 (95% confidence interval [CI] for the highest vs the lowest quartile, 1.59-3.18). The A(1c) levels correlated with several other traditional cardiovascular risk factors, and in fully adjusted models, the predictive effect of A(1c) was attenuated and not significant (RR for the highest vs the lowest quartile, 1.00; 95% CI, 0.65-1.54). In contrast, in the population including women with diabetes mellitus at enrollment, diabetes mellitus (RR, 4.97; 95% CI, 2.81-8.77) remained a strong independent determinant of cardiovascular risk in fully adjusted analyses, while A(1c) levels did not (RR for the highest vs the lowest quartile, 1.11; 95% CI, 0.73-1.71). CONCLUSIONS: The A(1c) level is associated with future cardiovascular risk among women without diabetes mellitus, but this relationship is largely attributable to a strong correlation with other cardiovascular risk factors. In contrast, diabetes mellitus is a strong independent determinant of cardiovascular risk, even after adjustment for A(1c) levels.

Potential cost-effectiveness of C-reactive protein screening followed by targeted statin therapy for the primary prevention of cardiovascular disease among patients without overt hyperlipidemia.

BACKGROUND: Evidence suggests that statin therapy reduces the rate of cardiovascular events among patients with low lipid levels but elevated C-reactive protein levels. However, no cost-effectiveness analyses have been performed to assist in determining whether large-scale randomized trials are merited to test this hypothesis. METHODS: We used a Markov model to estimate the benefits, costs, and incremental cost-effectiveness of C-reactive protein screening followed by targeted statin therapy for elevated C-reactive protein levels, compared with dietary counseling alone, for the primary prevention of cardiovascular events among patients with low-density lipoprotein cholesterol levels <149 mg/dL. All costs were in 2000 U.S. dollars. RESULTS: The potential incremental cost-effectiveness ratio for screening followed by statin therapy compared with no screening and no statin therapy was $48,100 per quality-adjusted life-year (QALY) for 58-year-old men and $94,400 per QALY for 58-year-old women. Screening was most cost-effective for 65-year-old men ($42,600 per QALY) and least cost-effective for 35-year-old women ($207,300 per QALY). Our results were most sensitive to the baseline risk of coronary heart disease, the cost of statin therapy, and the efficacy of statin therapy for preventing myocardial infarction in patients with high C-reactive protein levels. If a 58-year-old man who smokes and is hypertensive was considered, screening for C-reactive protein followed by statin therapy would be cost saving if the cost of statin therapy was reduced to $500 per year. If the cost of statin therapy was reduced to $1 per day, the cost-effectiveness of screening would be $4900 per QALY for 58-year-old men and $19,600 per QALY for women of the same age. If the costs associated with elective revascularization (percutaneous coronary intervention or coronary artery bypass surgery) were included in the base case analyses, the incremental cost-effectiveness ratios for screening would be $40,100 per QALY for 58-year-old men and $87,300 per QALY for women. CONCLUSION: A strategy involving C-reactive protein screening to target statin therapy for the primary prevention of cardiovascular disease among middle-aged patients without overt hyperlipidemia could be relatively cost-effective and, in some cases, cost saving.

Are statins anti-inflammatory?

Large scale clinical trials demonstrate significant reductions in cardiovascular event rates with statin therapy. The observed benefit of statin therapy, however, may be larger in these trials than that expected on the basis of lipid lowering alone. Emerging evidence from both clinical trials and basic science studies suggest that statins have anti-inflammatory properties, which may additionally lead to clinical efficacy. Measurement of markers of inflammation such as high sensitivity C-reactive protein in addition to lipid parameters may help identify those patients who will benefit most from statin therapy.

Rescue percutaneous coronary intervention following coronary artery bypass graft--a descriptive analysis of the changing interface between interventional cardiologist and cardiac surgeon.

BACKGROUND: Despite decreasing rates of acute and subacute complications of percutaneous coronary intervention (PCI), these procedures are generally only performed in centers where it is possible for failed PCI to be treated by rescue coronary artery bypass graft (CABG). Case reports and case series have documented successful PCI following failed CABG. We sought to confirm this decrease in the need for rescue CABG following failed PCI and to examine trends in the utilization of rescue PCI following failed CABG. HYPOTHESIS: The interface between interventional cardiologist and cardiac surgeon is characterized by changing practice patterns and resource utilization. METHODS: We examined the medical records of all patients admitted to the Brigham and Women's Hospital over a 7-year period and identified 169 patients who required both PCI and CABG during the same hospital admission. We describe and compare three predetermined groups of patients defined by the sequence of, and indication for, the relevant myocardial revascularization procedures. RESULTS: In all, 100 patients required CABG for failed PCI, 46 patients had planned hybrid procedures involving both CABG and PCI, and 23 patients required PCI following failed CABG. There was a decrease in the need for rescue CABG following failed PCI, both in total numbers and as a percentage of total cases (2.5% in 1994 and 0.22% in 1999). There was a simultaneous increase in the utilization of rescue PCI following failed CABG (0% in 1994 and 1.6% in 2000). Hybrid procedures were identified as a source of innovative solutions to a variety of challenging clinical problems. CONCLUSIONS: Changing patterns of resource utilization should be considered when planning hospital facilities and patient triage, and these patients undergoing percutaneous or surgical revascularization may benefit from close cooperation between the cardiac surgeon and the interventional cardiologist.

C-reactive protein and the risk of developing hypertension.

CONTEXT: Although it has been hypothesized that hypertension is in part an inflammatory disorder, clinical data linking inflammation with incident hypertension are scarce. OBJECTIVE: To examine whether C-reactive protein levels, a marker of systemic inflammation, are associated with incident hypertension. DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study that began in 1992 of 20 525 female US health professionals aged 45 years or older who provided baseline blood samples with initially normal levels of blood pressure (BP) (systolic BP <140 mm Hg and diastolic BP <90 mm Hg, and no history of hypertension or antihypertensive medications) and then followed up for a median of 7.8 years for the development of incident hypertension. Plasma C-reactive protein levels were measured and baseline coronary risk factors were collected. MAIN OUTCOME MEASURE: Incident hypertension, defined as either a new physician diagnosis, the initiation of antihypertensive treatment, or self-reported systolic BP of at least 140 mm Hg or a diastolic BP of at least 90 mm Hg. RESULTS: During follow-up, 5365 women developed incident hypertension. In crude models, the relative risks (RRs) and 95% confidence intervals (CIs) of developing hypertension from the lowest (referent) to the highest levels of baseline C-reactive protein were 1.00, 1.25 (95% CI, 1.14-1.40), 1.51 (95% CI, 1.35-1.68), 1.90 (95% CI, 1.72-2.11), and 2.50 (95% CI, 2.27-2.75) (linear trend P<.001). In fully adjusted models for coronary risk factors, the RRs and 95% CIs were 1.00, 1.07 (95% CI, 0.95-1.20), 1.17 (95% CI, 1.04-1.31), 1.30 (95% CI, 1.17-1.45), and 1.52 (95% CI, 1.36-1.69) (linear trend P<.001). C-reactive protein was significantly associated with an increased risk of developing hypertension in all prespecified subgroups evaluated, including those with very low levels of baseline BP, as well as those with no traditional coronary risk factors. Similar results were found when treating C-reactive protein as a continuous variable and controlling for baseline BP. CONCLUSION: C-reactive protein levels are associated with future development of hypertension, which suggests that hypertension is in part an inflammatory disorder.

MicroRNA Expression in Coronary Artery Disease.

The pathogenesis of atherosclerosis involves the interplay of inflammation, altered cellular activity, angiogenesis, and neointima formation. The main cellular participants in atherosclerosis include vascular endothelial cells, smooth muscle cells, and monocytes. The recent discovery of small, non-coding RNAs, microRNAs (miRNAs), and their influence on these processes has provided a greater molecular insight into atherosclerosis. This in turn has led to increase focus on the potential utility of miRNA subtypes as biomarkers for coronary artery disease. Furthermore miRNAs could potentially provide therapeutic targets for the treatment of atherosclerosis and its complications. In this review, we discuss the experimental and clinical evidence for the role of miRNAs in the pathogenesis of coronary artery disease, the limitations of the data and challenges facing the field.

A global perspective on psychosocial risk factors for cardiovascular disease.

Worldwide, there is variation in the incidence CVD with the greater burden being borne by low and middle-income countries. Traditional risk factors do not fully explain the CVD risk in populations, and there is increasing awareness of the impact the social environment and psychological factors have on CVD incidence and outcomes. The measurement of psychosocial variables is uniquely complex as variables are difficult to define objectively and local understanding of psychosocial risk factors may be subject to cultural influences. Notwithstanding this, there is a growing evidence base for the independent role they play in the pathogenesis of CVD. Consistent associations have been seen for general psychological stress, work-related stress, locus of control and depression with CVD risk. Despite the strength of this association the results from behavioural and pharmacological interventions have not clearly resulted in improved outcomes.