Low Framingham Risk Score Research Articles

Case report: Low circulating IGF-I levels due to Acid-Labile Subunit deficiency in adulthood are not associated with early development of atherosclerosis and impaired heart function

ObjectiveDecreased insulin-like growth factor-I (IGF-I) levels in adults have been associated with an increased risk of ischemic heart disease and heart failure. It is currently unknown whether patients with low circulating IGF-I levels due to a homozygous acid-labile subunit (IGFALS) gene mutation also have increased risk of cardiovascular disease. Therefore, we evaluated atherosclerotic burden in a 27year old male patient who was diagnosed with a homozygous IGFALS mutation and consequently had extremely low circulating IGF-I levels. MethodsTen year's cardiovascular risk was calculated using the Framingham risk score. Presence of (subclinical) atherosclerosis was assessed using a 64-slice CT scan of the coronary arteries. Cardiac performance was measured by conventional echocardiographic measurements, three dimensional (3D)-echocardiography, and tissue deformation imaging. ResultsDespite his extremely low circulating IGF-I levels due to Acid-Labile Subunit (ALS) deficiency, our patient had a low Framingham risk score and no signs of coronary atherosclerosis. Adjusted for physical height, cardiac performance was not impaired compared with healthy subjects. ConclusionThe present case report does not lend support to routine cardiovascular screening in patients with extremely low circulating IGF-I levels due to a homozygous IGFALS mutation, when cardiovascular risk is low.

Carotid Ultrasound Identifies High Risk Subclinical Atherosclerosis in Adults with Low Framingham Risk Scores

Conclusion: A high percentage of young to middle-aged individuals with a Framingham Risk Score (FRS) indicating <5% risk of cardiovascular events have abnormal carotid ultrasound findings associated with an increased risk for cardiovascular events. Summary: Atherosclerosis-related clinical events are presumably preceded by a period of asymptomatic atherosclerosis. The FRS is a population-based algorithm recommended to identify at-risk individuals and determine the aggressiveness of preventive therapy (JAMA 2001;285:2486-97). However, population-based risk algorithms do not quantify atherosclerosis. They provide only a probability of cardiovascular events over a relatively short fixed period, usually <10 years. The FRS risk assessment also does not incorporate family history, premature coronary artery disease, remote smoking history, impaired fasting glucose, triglyceride levels, or waist circumference. Tests for subclinical atherosclerosis are therefore sometimes recommended to add incremental information and provide more accurate risk stratification. The authors tested the hypothesis that patients with a low (<5%) FRS 10-year risk for a first cardiovascular event and intermediate (6% to 20%) FRS 10-year risk will have increased cardiovascular risk as determined by an abnormal carotid intima-media thickness (IMT). This study included individuals aged <65 years who were not taking statins and who did not have diabetes or a history of coronary artery disease, but who did undergo a determination of carotid IMT and plaque for primary intervention. Clinical variables analyzed included lipid values, family history of coronary artery disease, FRS, and subsequent pharmacotherapy recommendations. The study comprised 441 individuals who were a mean age of 49.7 ± 7.9 years. Of these patients, 184 (42%, 95% CI, 37.3%-46.5%) had high-risk carotid IMT findings (carotid IMT ≥75th percentile adjusted for age, sex, race, or presence of plaque). In 336 individuals with the lowest FRS score of <5%, 127 (38%, 95% CI, 32.6%-43.0%) had high-risk carotid ultrasound findings. The treating physicians recommended lipid-lowering therapy for 77 individuals (61%) with a FRS ≤5% and high-risk carotid ultrasound findings. Comment: This study indicates a disconnect between the risk assessment by the FRS and carotid IMT. Studies have also found high-risk carotid ultrasound findings influence physicians to prescribe aspirin or lipid-lowering therapies (Wyman RA, et al; Am Heart J 2007;154:1072-7 and Korcarz CE, et al; J Am Soc Echocardiogr 2008;21:1156-62). However, although physicians may make treatment decisions based on a finding of increased carotid IMT, it appears that observing changes in IMT to monitor effects of drug therapy will not reduce subsequent clinical events. A practical point may be that carotid IMT can be used to identify patients at increased risk for cardiovascular events, but once treatment is initiated, subsequent studies to monitor effectiveness of treatment may not be needed.

Microvascular Function Predicts Cardiovascular Events in Primary Prevention

Background— Biomarkers of atherosclerosis may refine clinical decision making in individuals at risk of cardiovascular disease. The purpose of the study was to determine the prognostic significance of endothelial function and other vascular markers in apparently healthy men. Methods and Results— The cohort consisted of 1574 men (age, 49.4 years) free of vascular disease. Measurements included flow-mediated dilation and its microvascular stimulus, hyperemic velocity, carotid intima-media thickness, and C-reactive protein. Cox proportional hazard models evaluated the relationship between vascular markers, Framingham risk score, and time to a first composite cardiovascular end point of vascular death, revascularization, myocardial infarction, angina, and stroke. Subjects had low median Framingham risk score (7.9%). Cardiovascular events occurred in 71 subjects (111 events) over a mean follow-up of 7.2±1.7 years. Flow-mediated dilation was not associated with subsequent cardiovascular events (hazard ratio, 0.92; P =0.54). Both hyperemic velocity (hazard ratio, 0.70; 95% confidence interval, 0.54 to 0.90; P =0.006) and carotid intima-media thickness (hazard ratio, 1.45; confidence interval, 1.15 to 1.83; P =0.002) but not C-reactive protein ( P =0.35) were related to events in a multivariable analysis that included Framingham risk score (per unit SD). Furthermore, the addition of hyperemic velocity to Framingham risk score resulted in a net clinical reclassification improvement of 28.7% ( P &lt;0.001) after 5 years of follow-up in the intermediate-risk group. Overall net reclassification improvement for hyperemic velocity was 6.9% ( P =0.24). Conclusions— In men, hyperemic velocity, the stimulus for flow-mediated dilation, but not flow-mediated dilation itself was a significant risk marker for adverse cardiovascular outcomes. The prognostic value was additive to traditional risk factors and carotid intima-media thickness. Hyperemic velocity, a newly described marker of microvascular function, is a novel tool that may improve risk stratification of lower-risk healthy men.

Epicardial Fat: An Additional Measurement for Subclinical Atherosclerosis and Cardiovascular Risk Stratification?

The value of epicardial adipose tissue (EAT) thickness as determined by echocardiography in cardiovascular risk assessment is not well understood. The aim of this study was to determine the associations between EAT thickness and Framingham risk score, carotid intima media thickness, carotid artery plaque, and computed tomographic coronary calcium score in a primary prevention population. Patients presenting for cardiovascular preventive care (n = 356) who underwent echocardiography as well as carotid artery ultrasound and/or coronary calcium scoring were included. EAT thickness was weakly correlated with Framingham risk score. The prevalence of carotid plaque was significantly greater in those with EAT thickness ≥ 5.0 mm who either had low Framingham risk scores or had body mass indexes ≥ 25 kg/m(2), compared with those with EAT thickness <5.0 mm. No significant association between EAT thickness and carotid intima-media thickness or coronary calcium score existed. EAT thickness ≥ 5.0 mm may identify an individual with a higher likelihood of having detectable carotid atherosclerosis.

Prevalence of low ankle-brachial index, elevated plasma fibrinogen and CRP across Framingham risk categories: Data from the National Health and Nutrition Examination Survey (NHANES) 1999–2004

Objective60–80% of heart attacks or coronary-related deaths occur in individuals identified as non-high-risk per the conventional risk assessment algorithms. Abnormal ankle-brachial index (ABI), plasma fibrinogen and plasma C-reactive protein (CRP) have been shown to be associated with a higher risk of cardiovascular disease (CVD). However, comparable data have not been reported for prevalence of abnormal ABI, fibrinogen and CRP in non-high-risk population. MethodsWe analyzed data from the 1999–2004 National Health and Nutrition Examination Survey (NHANES), a nationally representative cross-sectional survey of the U.S. population, for 6292 men and women, aged 40 and older, without known CVD or diabetes, with available data on standard CVD risk factors, ABI, fibrinogen and CRP. The main objective was to identify proportions of individuals with abnormal ABI (ABI<0.9 in either leg), elevated fibrinogen (≥400mg/dl), and elevated CRP (>3mg/l), with otherwise low or intermediate (<20%) 10-year Framingham risk score. ResultsOverall prevalence of abnormal ABI, fibrinogen, and CRP was 3.6% (95% CI 3.2–4.1%), 27.4% (95% CI 23.9–31.0%) and 38.3% (95% CI 36.5–40.0%) respectively. Among those with ABI data, 91.4% were at <20% FRS, and of these only 2.7% (95% CI 2.3–3.1%, p<0.0001) had an abnormal ABI. Among those with fibrinogen data, 90.8% were at <20% FRS, and of these 23.6% (95% CI 20.4–26.8%, p<0.001) had elevated plasma fibrinogen. Among those with CRP data, 91.1% were at <20% FRS, and of these 34.3% (95% CI 32.7–36.0%, p=0.0012) had an elevated CRP. Overall, 45.0% (95% CI 42.2–47.8%; p<0.0001) had abnormal ABI, fibrinogen or CRP but low-intermediate risk. ConclusionAbnormal ABI, elevate fibrinogen and CRP are highly prevalent among individuals otherwise at low-intermediate risk. If any or all of them are shown to improve predictive ability of FRS for primary prevention, it would have a significant public health impact.

Common Carotid Intima-Media Thickness and Framingham Risk Score Predict Incident Carotid Atherosclerotic Plaque Formation

Cross-sectional studies describe a positive association between common carotid artery intima-media thickness (CCA-IMT) and carotid plaques (CP). However, longitudinal data on the predictive value of CCA-IMT for occurrence of CP are limited. Therefore, the role of increasing CCA-IMT in the atherosclerotic process is still discussed controversially. We investigated the predictive value of CCA-IMT and the Framingham risk score (FRS) for incident CP formation in a population-based longitudinal study of 1922 subjects aged 45 to 81 years who underwent ultrasonography of both carotid arteries and received vascular risk factor assessment at baseline and after 5 years. CP was defined as any protruding focal thickening of the intima-media complex. Incident CP formation during follow-up was defined as the appearance of at least 1 CP in a previously plaque-free arterial segment (right and left common, internal, and external carotid arteries and carotid bifurcation). Among the 636 subjects without CP at baseline, 418 (66%) had at least 1 incident CP during follow-up. In a multivariable negative binominal regression model adjusted for age, gender, and the FRS, the number of arterial segments affected by incident CP was 1.53-fold higher (CI, 1.12-2.07; P<0.01) for subjects in the highest quartile of the overall CCA-IMT distribution compared to those in the lowest quartile. Both CCA-IMT and FRS independently predict incident CP formation. The risk of CP formation may actually be underestimated in subjects with low FRS and high IMT.

Carotid Ultrasound Identifies High Risk Subclinical Atherosclerosis in Adults with Low Framingham Risk Scores

Worldwide, cardiovascular (CV) disease remains the most common cause of morbidity and mortality. Although effective in predicting CV risk in select populations, the Framingham risk score (FRS) fails to identify many young individuals who experience premature CV events. Accordingly, the aim of this study was to determine the prevalence of high-risk carotid intima-media thickness (CIMT) or plaque, a marker of atherosclerosis and predictor of CV events, in young asymptomatic individuals with low and intermediate FRS (<2% annualized event rate) using the carotid ultrasound protocol recommended by the American Society of Echocardiography and the Society of Vascular Medicine. Individuals aged < or = 65 years not taking statins and without diabetes mellitus or histories of coronary artery disease underwent CIMT and plaque examination for primary prevention. Clinical variables including lipid values, family history of premature coronary artery disease, and FRS and subsequent pharmacotherapy recommendations were retrospectively collected for statistical analysis. Of 441 subjects (mean age, 49.7 + or - 7.9 years), 184 (42%; 95% confidence interval, 37.3%-46.5%) had high-risk carotid ultrasound findings (CIMT > or = 75th percentile adjusted for age, gender, and race or presence of plaque). Of those with the lowest FRS of < or =5% (n = 336) (mean age, 48.0 + or - 7.6 years; mean FRS, 2.5 + or - 1.5%), 127 (38%; 95% confidence interval, 32.6%-43.0%) had high-risk carotid ultrasound findings. For individuals with FRS < or = 5% and high-risk carotid ultrasound findings (n = 127; mean age, 47.3 + or - 8.1 years; mean FRS, 2.5 + or - 1.5%), lipid-lowering therapy was recommended by their treating physicians in 77 (61%). Thirty-eight percent of asymptomatic young to middle-aged individuals with FRS < or = 5% have abnormal carotid ultrasound findings associated with increased risk for CV events. Pharmacologic therapy for CV prevention was recommended in the majority of these individuals. The lack of radiation exposure, relatively low cost, and ability to detect early-stage atherosclerosis suggest that carotid ultrasound for CIMT and plaque detection should continue to be explored as a primary tool for CV risk stratification in young to middle-aged adults with low FRS.

High Prevalence of Ultrasound Detected Carotid Atherosclerosis in Subjects with Low Framingham Risk Score: Potential Implications for Screening for Subclinical Atherosclerosis

The cardiovascular (CV) risk assigned by the Framingham risk score (FRS) misses many subjects destined for CV events. Coronary artery calcification (CAC) as measured by computed tomography and carotid intima-media thickness (CIMT) and plaque assessment using B-mode ultrasound can identify subclinical atherosclerosis. The comparative relation of CAC and CIMT and carotid plaque after integration into the FRS is not established. The aim of this study was to develop a CV screening approach incorporating FRS, CAC, and CIMT. The prevalence of subclinical atherosclerosis, defined as CAC score > 0, CIMT > or = 75th percentile, or plaque > or = 1.5 mm, was determined in the groups with low, intermediate, and high FRS among 136 asymptomatic subjects. The CIMT and CAC values were used to determine "vascular age" and "coronary calcium" age, respectively, with established nomograms. In the 103 low-risk (FRS < 10%) subjects, 41%, 50%, 59%, and 66% had CAC scores > 0, CIMT > or = 75th percentile, plaque > or = 1.5 mm, and CIMT > or = 75th percentile or plaque > or = 1.5 mm, respectively. In the 33 subjects with intermediate (n = 14) or high (n = 19) FRS, 70%, 81%, 87%, and 87% had CAC scores > 0, CIMT > or = 75th percentile, plaque > or = 1.5 mm, and CIMT > or = 75th percentile or plaque > or = 1.5 mm, respectively. Fifty-two percent of subjects with coronary calcium scores of zero had carotid plaque. Adjusted for FRS, body mass index was an independent predictor of abnormal CIMT in the low-FRS group, but not of abnormal CAC. Mean vascular CIMT age was significantly higher than coronary calcium age (61.6 + or - 11.4 vs 58.3 + or - 11.1 years, P = .001), and both were significantly higher than chronologic age (56.9 + or - 10.1 years) (P < .0001 and P < .04, respectively). CIMT upgraded or downgraded FRS by >5% in more cases than CAC (42% vs 17%). In asymptomatic patients without CV disease, CIMT and plaque assessment are more likely to revise FRS than CAC. Body mass index predicts increased CIMT in low-FRS subjects. These findings may have broad implications for screening in low-FRS subjects.

Coronary Heart Disease Risk Prediction in the Era of Genome-Wide Association Studies

For DNA-based tests that assess genetic predisposition to coronary heart disease (CHD) to be of clinical value, they need to provide information over and above conventional risk factors (CRFs) currently used in risk algorithms, such as the Framingham Risk Score,1 which incorporates CRFs such as age, gender, blood lipid concentrations, blood pressure, body mass index, family history, and smoking habit. To achieve this, several hurdles must be passed. The first challenge is to identify a set of common single-nucleotide polymorphisms (SNPs) at loci associated with CHD risk. Over the last 10 to 15 years, this has been done by use of a “candidate gene” approach through association studies in prospective analysis or case-control studies, ie, comparing SNP genotype or allele frequency between groups of individuals with CHD and healthy subjects. Several of the genes, chosen because of their key role in processes that predispose to atherosclerosis, have meta-analysis–confirmed effects on risk of CHD,2 the best example of which is the APOE gene, which encodes apolipoprotein E, with 3 common isoforms that are associated with strong effects on plasma lipids and more modest effects on risk of CHD.3 This “hypothesis-driven” search for useful genetic variants provides the foundation for the development of genetic CHD risk profiles, and in the last 2 years, it has been enhanced by technical advances that have allowed “hypothesis-free” genome-wide association studies (GWASs), primarily in a case-control setting. Although the list of identified CHD-risk loci and SNPs will clearly grow, we have at least the basis to start the examination of their potential clinical utility. The second set of challenges is to obtain a robust estimate of the size of the risk effects associated with these SNPs. This requires population-based prospective studies to avoid bias, because estimates in the case-control setting, although efficient for …

The USPSTF Recommendation Statement on Coronary Heart Disease Risk Assessment

Letters16 March 2010The USPSTF Recommendation Statement on Coronary Heart Disease Risk AssessmentRobert J. Glynn, PhD, ScDRobert J. Glynn, PhD, ScDFrom Brigham & Women's Hospital, Harvard Medical School, Boston, MA 02115.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-152-6-201003160-00015 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:The statement from the U.S. Preventive Services Task Force (USPSTF) (1) that “persons with low (<10%) Framingham risk scores do not benefit from aggressive risk factor modification” and the conclusion that high-sensitivity C-reactive protein (CRP) does not improve a physician's ability to guide treatment do not reflect current randomized trial data. The USPSTF conclusions should be of particular concern for women, almost all of whom have Framingham risk scores less than 10%.JUPITER (Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin) (2) studied apparently healthy men and women with high-sensitivity CRP ...

CAROTID ULTRASOUND IDENTIFIES HIGH RISK SUBCLINICAL ATHEROSCLEROSIS IN ADULTS WITH LOW FRAMINGHAM RISK SCORES

Background Worldwide, cardiovascular (CV) disease remains the most common cause of morbidity and mortality. Although effective in predicting CV risk in select populations, the Framingham risk score (FRS) fails to identify many young individuals who experience premature CV events. Accordingly, the aim of this study was to determine the prevalence of high-risk carotid intima-media thickness (CIMT) or plaque, a marker of atherosclerosis and predictor of CV events, in young asymptomatic individuals with low and intermediate FRS ( Methods Individuals aged ≤ 65 years not taking statins and without diabetes mellitus or histories of coronary artery disease underwent CIMT and plaque examination for primary prevention. Clinical variables including lipid values, family history of premature coronary artery disease, and FRS and subsequent pharmacotherapy recommendations were retrospectively collected for statistical analysis. Results Of 441 subjects (mean age, 49.7 ± 7.9 years), 184 (42%; 95% confidence interval, 37.3%-46.5%) had high-risk carotid ultrasound findings (CIMT ≥ 75th percentile adjusted for age, gender, and race or presence of plaque). Of those with the lowest FRS of ≤5% (n = 336) (mean age, 48.0 ± 7.6 years; mean FRS, 2.5 ± 1.5%), 127 (38%; 95% confidence interval, 32.6%-43.0%) had high-risk carotid ultrasound findings. For individuals with FRS ≤ 5% and high-risk carotid ultrasound findings (n = 127; mean age, 47.3 ± 8.1 years; mean FRS, 2.5 ± 1.5%), lipid-lowering therapy was recommended by their treating physicians in 77 (61%). Conclusions Thirty-eight percent of asymptomatic young to middle-aged individuals with FRS ≤ 5% have abnormal carotid ultrasound findings associated with increased risk for CV events. Pharmacologic therapy for CV prevention was recommended in the majority of these individuals. The lack of radiation exposure, relatively low cost, and ability to detect early-stage atherosclerosis suggest that carotid ultrasound for CIMT and plaque detection should continue to be explored as a primary tool for CV risk stratification in young to middle-aged adults with low FRS.

The role of calcium score and CT angiography in the medical management of patients with normal myocardial perfusion imaging

BackgroundIndividuals with normal myocardial perfusion imaging (MPI) may still have substantial coronary artery disease (CAD), which would benefit from aggressive medical therapy. The role of coronary artery calcium-score (CAC) and/or coronary CT Angiography (CTA) to identify additional treatment candidates in this population is unknown. MethodsNinety-four patients completed the study protocol and underwent CAC and CTA after MPI. ResultsIn 81 patients who had a normal MPI, an algorithm using the clinical predictors, CAC, and then CTA was created to identify candidates for aggressive medical management; 24/81 patients had a high Framingham Risk Score (FRS) or diabetes, and need aggressive medical management, while 6/81 patients had a low FRS and low post-MPI probability of CAD. The use of CAC in 51/81 patients with intermediate clinical predictors would identify 23/51 patients with low risk (CAC < 100) and 11/51 patients (CAC > 400) for aggressive medical management. The remaining 17/51 patients with intermediate CAC scores (100-399) would require CTA, of which, would identify 8/17 additional patients with >50% stenosis for aggressive medical therapy. ConclusionA stepwise approach including history, CAC and CTA can identify about 50% of the patients with normal MPI who have a higher risk and may benefit from aggressive medical management.

Prevalence and Distribution of Sub-Clinical Atherosclerosis by Screening Vascular Ultrasound in Low and Intermediate Risk Adults: The New York Physicians Study

Many persons experiencing cardiovascular disease (CVD) events are not at high calculated CVD risk by Framingham risk score. The identification of carotid and femoral plaque has been associated with CVD events. In this study, the prevalence of plaques in adults at low and intermediate risk was examined. Asymptomatic patients without CVD (n = 715; 43% women) were screened for carotid and femoral plaque using B-mode ultrasound. Significant predictors of plaque were male gender and age and, among women, dyslipidemia. Overall plaque prevalence was 32.8% among women and 40.5% among men aged 50 to 64 years. Among subjects with plaque in this age group, 56% of women and 31% of men had plaque exclusively in the femoral artery and would have been missed if only carotid ultrasound had been performed. Ultrasound screening of the carotid and femoral arteries in a population with low and intermediate Framingham risk scores can identify potentially high risk subjects for whom intensive CVD risk factor modification may be appropriate.

Framingham risk score after risk-reducing salpingo-oophorectomy in women at risk for hereditary breast ovarian cancer: A controlled observational study

11048 Background: Risk-reducing salpingo-oophorectomy (RRSO) effectively prevents ovarian cancer in BRCA mutation carriers and in women at risk for hereditary breast-ovarian cancer. RRSO induces immediate menopause, which may increase the risk of coronary heart disease (CHD). Our aim was to determine CHD risk using Framingham risk score and examine factors associated with this risk in women who had undergone RRSO compared to population-based controls. Methods: A sample of 326 (65% of invited) women who underwent RRSO after genetic counseling from 1980–2005 provided completed questionnaires, physical measures, and blood samples. Controls were 1,630 age-matched controls from the Norwegian Nord-Trøndelag Health Study (HUNT-2) (1995- 97). Results: Mean age in both the RRSO and control groups at survey was 54.4 years. Mean follow-up after surgery was 6.5 years (SD 4.4). The RRSO group had a more favorable CHD risk profile (higher education, more physical activity, less smoking, lower total cholesterol, higher HDL cholesterol, lower systolic blood pressure and lower BMI) and lower Framingham total score compared to controls (p&lt;0.05). In multiple logistic regression analyses RRSO was inversely associated with Framingham 10-year risk ≥5% (Odds Ratio 0.49, 95% CI [0.34, 0.71] p&lt;0.001). Conclusions: In contrast to expectation, women at increased risk of hereditary breast ovarian cancer had a favorable CHD risk profile after RRSO compared to age-matched controls from the general population, and RRSO was associated with lower Framingham risk score. Follow-up time, self-selection of women seeking genetic counseling, changes in lifestyle after surgery and survival bias are possible explanations of this finding. No significant financial relationships to disclose.

Efficacy and safety of rosuvastatin in the management of dyslipidemia

Rosuvastatin is a synthetic statin that represents an advance in the pharmacologic and clinical properties of statins. Relative to other statins, rosuvastatin possesses a greater number of binding interactions with HMG-CoA reductase and has a high affinity for the active site of the enzyme. As with other statins, serious adverse effects with rosuvastatin therapy are uncommon and primarily involve effects on the liver and skeletal muscle. The risk increases with increasing dosages and coadministration with other drugs interacting with the same metabolic pathway. The degree of LDL reduction is important to achieve the treatment goals suggested by international guidelines. Among the most potent statins, rosuvastatin is capable of getting the majority of patients to their LDL cholesterol goals. In addition, rosuvastatin has been found effective in reducing small-dense LDL, C-reactive protein and in increasing HDL cholesterol levels. Controlled clinical trials using vascular end-points have been performed. In particular, a study demonstrated that rosuvastatin therapy could slow progression and/or cause regression of carotid intima-media thickness over 2 years in middle-aged individuals with a low Framingham risk score (FRS) and mild to moderate subclinical atherosclerosis. A primary prevention study (JUPITER) was stopped before the programmed end of the study, because of excess benefit for high-risk individuals receiving rosuvastatin treatment. It is suggested that pronounced LDL reduction, in association with significant HDL cholesterol increase, are the bases of a marked preventive action of rosuvastatin. The results from JUPITER support the use of rosuvastatin for primary cardiovascular prevention, in overweight men and women, with near to normal LDL cholesterol and high CRP. There is now evidence of benefit from rosuvastatin treatment for a wide segment of the general population at intermediate cardiovascular risk. In absolute numbers, this segment represents the main source of cardiovascular events: on the basis of JUPITER results, it is expected that treatment target and potential candidates to statin therapy will be reevaluated and redefined.

Cardiac Diastolic Dysfunction Is Prevalent in HIV-Infected Patients

Combination antiretroviral therapy (ART) has markedly improved survival in HIV-infected patients, but not without significant adverse effects including ART-associated dyslipdemia and insulin resistance, which may in part contribute to an increased risk of cardiovascular events. Other contributing factors to cardiovascular risk may include uncontrolled HIV replication, the effects of HIV and ART on vascular endothelium and inflammatory cytokines. Diastolic dysfunction may be an early sign of cardiovascular disease. Our objective was to determine the prevalence of diastolic dysfunction in HIV-infected patients without cardiovascular symptoms. We enrolled 91 subjects in a cross-sectional study of HIV-infected patients without cardiovascular symptoms between September 2004 and August 2005, to assess whether demographics, HIV-related factors, cardiac risk factors, and ART were associated with diastolic dysfunction. All subjects underwent two-dimensional transthoracic echocardiography with tissue Doppler imaging. Subjects were predominately male with a median age of 38 (interquartile range [IQR]: 33, 42) years and median ART duration 6.15 (IQR: 2.1, 8.4) years. Subjects had low Framingham risk scores. Diastolic dysfunction was observed in 34 patients (37%; 95% confidence interval [CI] 27.4, 48.1). Cardiac risk factors or poor prognostic indicators of AIDS progression were uncommon with no difference between subjects with or without diastolic dysfunction. A nonstatistically significant trend in increased rate of diastolic dysfunction was observed in patients receiving protease inhibitors 1 year or more, 44% versus 28%, respectively (univariate odds ratio 2.02, 95% CI 0.83 to 4.90). This was not observed with prolonged use of either non-nucleoside or nucleoside reverse transcriptase inhibitors. A high prevalence of diastolic dysfunction (37%) in a cohort of HIV-infected patients on ART at low risk for AIDS and cardiovascular disease was demonstrated.

Carotid intima-media thickness and coronary artery calcium score as indications of subclinical atherosclerosis.

To determine the ability of carotid intima-media thickness (CIMT) and coronary artery calcium score (CACS) to detect subclinical atherosclerosis in a young to middle-aged, low-risk, primary-prevention population. Patients aged 36 to 59 years who underwent determination of CIMT and CACS at our institution between May 1, 2004, and April 1, 2008, were included in the study. Those with diabetes mellitus or a history of coronary, peripheral, or cerebral vascular disease were excluded. Other information, such as Framingham risk score (FRS), was obtained by a review of clinical and laboratory data. Of 118 patients, 89 (75%) had a CACS of zero and 94 (80%) were men; mean +/- SD age was 48.9+/-5.7 years. The mean FRS of this group was 4.0; 86 patients (97%) were considered at low risk (<1% annualized rate) of cardiovascular events. Evidence of carotid atherosclerosis was found in 42 (47%; 95% confidence interval, 37%-58%) of these 89 patients; carotid plaque was found in 30 (34%); and CIMT above the 75th percentile was found in 12 (13%) of age-, sex-, and race-matched control patients. Of the 40 patients with low-risk CIMT (below the 50th percentile), 4 (10%) had a CACS at or above the 50th percentile. Subclinical vascular disease can be detected by CIMT evaluation in young to middle-aged patients with a low FRS and a CACS of zero. These findings have important implications for vascular disease screening and the implementation of primary-prevention strategies.

Prevalence of coronary artery disease across the Framingham risk categories: coronary artery calcium scoring and MSCT coronary angiography

BackgroundNon-invasive assessment of subclinical atherosclerosis by means of coronary artery calcium scoring (CACS) and multi-slice computed tomography (MSCT) coronary angiography could improve patients’ risk stratification. However, data relating observations on CACS and MSCT coronary angiography to traditional risk assessment are scarce. Methods and ResultsIn 314 consecutive outpatients (54 ± 13 years, 56% males) without known CAD, CACS and 64-slice MSCT coronary angiography were performed. According to the Framingham risk score (FRS), 51% of patients were at low, 24% at intermediate and 25% at high risk, respectively. MSCT angiograms showing atherosclerosis were classified as showing obstructive (≥50% luminal narrowing) CAD or not. Both CACS and MSCT coronary angiography showed a high prevalence of normal coronary arteries in low FRS patients (70% and 61%, respectively). An increase in the prevalence of CACS >400 (4% low vs 19% intermediate vs 36% high), CAD (39% low vs 79% intermediate vs 91% high), and obstructive CAD (15% low vs 43% intermediate vs 58% high) was observed across the FRS categories (P < .0001 for all comparisons). ConclusionsA strong positive relationship exists between FRS and the prevalence and extent of atherosclerosis. Especially in intermediate FRS patients, CACS and MSCT coronary angiography provide useful information on the presence of subclinical atherosclerosis.

Prevalence of Emerging Cardiovascular Risk Factors in Younger Individuals with a Family History of Premature Coronary Heart Disease and Low Framingham Risk Score

The purpose of this study was to assess the prevalence of emerging cardiac risk factors in individuals with a family history of premature coronary heart disease (CHD) and who were predicted to be low-risk for cardiovascular (CV) disease based on their Framingham risk score. We prospectively evaluated 89 younger men and women with a family history of premature CHD and who had a low Framingham risk score. Patients with CHD or CHD equivalents were excluded. All patients were screened for emerging clinical and lipid risk factors. Coronary calcium was present in 38% of patients and C-reactive protein > 3 mg/dl was present in 24% of patients. Low levels of high-density lipoprotein (HDL2) cholesterol were the most prevalent emerging lipid risk factor and was present in 72% of the study group. More individuals had low levels of HDL2 than total HDL (34% versus 71%; p-value =0.001). Triglyceride- (TG)-rich remnant lipoproteins were present in 49% of patients. The Framingham risk score poorly predicts CV risk in younger healthy persons with a family history of premature CHD. The prevalence of subclinical CHD and emerging clinical and lipid risk factors is high in these patients. The most prevalent lipid risk factor was low levels of HDL2. Individuals with a family history of premature CHD may benefit from screening for emerging risk factors to better assess their CV risk.

Novel Measures of Heart Rate Variability Predict Cardiovascular Mortality in Older Adults Independent of Traditional Cardiovascular Risk Factors: The Cardiovascular Health Study (CHS)

Novel HRV Predicts CV Mortality in the Elderly. It is unknown whether abnormal heart rate turbulence (HRT) and abnormal fractal properties of heart rate variability identify older adults at increased risk of cardiovascular death (CVdth). Data from 1,172 community-dwelling adults, ages 72 +/- 5 (65-93) years, who participated in the Cardiovascular Health Study (CHS), a study of risk factors for CV disease in people >or=65 years. HRT and the short-term fractal scaling exponent (DFA1) derived from 24-hour Holter recordings. HRT categorized as: normal (turbulence slope [TS] and turbulence onset [TO] normal) or abnormal (TS and/or TO abnormal). DFA1 categorized as low (<or=1) or high (>1). Cox regression analyses stratified by Framingham Risk Score (FRS) strata (low = <10, mid = 10-20, and high >20) and adjusted for prevalent clinical cardiovascular disease (CVD), diabetes, and quartiles of ventricular premature beat counts (VPCs). CVdths (N = 172) occurred over a median follow-up of 12.3 years. Within each FRS stratum, low DFA1 + abnormal HRT predicted risk of CVdth (RR = 7.7 for low FRS; 3.6, mid FRS; 2.8, high FRS). Among high FRS stratum participants, low DFA1 alone also predicted CVdth (RR = 2.0). VPCs in the highest quartile predicted CVdth, but only in the high FRS group. Clinical CV disease predicted CVdth at each FRS stratum (RR = 2.9, low; 2.6, mid; and 1.9, high). Diabetes predicted CVdth in the highest FRS group only (RR = 2.2). The combination of low DFA1 + abnormal HRT is a strong risk factor for CVdth among older adults even after adjustment for conventional CVD risk measures and the presence of CVD.