Framingham 10-year Coronary Heart Disease Research Articles

Transient ischemic dilatation with adenosine 99mTc-sestamibi stress: prognostic significance in patients with normal myocardial perfusion.

To determine the significance of transient ischemic dilatation (TID) in patients with normal perfusion on adenosine stress/rest. We analyzed 430 consecutive patients with normal perfusion on 2-day adenosine stress/rest 99mTc-sestamibi. A group of 70 patients with Framingham 10-year coronary heart disease risk < 10% was used to derive abnormal TID thresholds (derivation group). The significance of TID at these thresholds was validated in the remaining 360 patients (validation group) followed for cardiac events for 31.2 ± 9.7 (mean ± SD) months. Transient ischemic dilatation in the derivation group was 1.05 ± 0.13. Three definitions of an abnormal TID were used: > mean + 2SD (TID ≥ 1.32), > mean + 1SD (TID ≥ 1.19) and a TID in the group's highest quartile (TID ≥ 1.15). Of the 360 validation group patients, 12 (3.3%), 48 (13.3%) and 70 (19.4%) had TID ≥ 1.32, 1.19 and 1.15, respectively. Age, gender, family history of coronary artery disease (CAD), known CAD, smoking, hypertension, diabetes, dyslipidemia, rest LVEF, post-stress LVEF, ΔLVEF, ≥ 5% or 10% decrease in LVEF did not predict TID ≥ 1.32. However, TID ≥ 1.19 was predicted by rest LVEF and ≥ 5% decrease in LVEF (P = 0.04 and 0.02, respectively) and TID ≥ 1.15 was predicted by ≥ 5% decrease in LVEF (P = 0.02). Cardiac event-free survivals were similar in patients with a TID ≥ and < 1.32 (P = 0.68), ≥ and < 1.19 (P = 0.40) and ≥ and < 1.15 (P = 0.79). Transient ischemic dilatation does not confer adverse prognosis in patients with normal perfusion on adenosine stress/rest 99mTc-sestamibi irrespective of the threshold used for its definition.

Advantages of Continuous-Valued Risk Scores for Predicting Long-Term Costs: The Framingham Coronary Heart Disease 10-Year Risk Score.

Background:The few studies that have examined the relationship between midlife cardiovascular disease risk and longer-term costs have differentiated risk using a small number of risk categories. In this paper, we illustrate the advantages of a continuous-valued score to examine the relationship between risk and longer-term costs: the Framingham 10-year coronary heart disease risk score.Methods:Our study cohort consisted of 1333 Second Generation Framingham Heart Study participants enrolled in fee-for-service Medicare for at least 8 quarters and who had a risk score assessment between age 40 and 50 years. We used generalized linear models to examine the relationships between quarterly Medicare costs and risk scores.Results:Using risk categories defined by the Framingham score, the cost differences between a low and high risk group were 40% to over 200% greater than differences in comparable studies using a small number of risk categories. A continuous-valued score facilitates comparison of the cost consequences of impacting risk score changes. For example, an intervention that is able to reduce a person’s score change between midlife and later-life from the 75th percentile to the 25th percentile would result in almost a 20% reduction in longer-term costs. In contrast, an intervention that is able to reduce a person’s midlife score from the 75th percentile to the 25th percentile would result in a 38% reduction in costs.Conclusions:A continuous-valued risk score has advantages compared to defining risk based on a small number of risk categories.

Abstract P164: Cognitive Impairment Among Adults With Incident Heart Failure

Background: Cognitive impairment is as high as 70% among adults with heart failure (HF) and its prevalence increases with the duration and severity of HF. However, little is known about the prevalence of cognitive impairment early in the course of HF. This is important, as high cognitive impairment at diagnosis would suggest that earlier screening would be warranted. We examined the prevalence and correlates of cognitive impairment among adults with incident HF. Methods: We used data from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study, an observational, longitudinal cohort study of 30,239 community-dwelling adults &gt; 45 recruited from 2003 to 2007. Blacks and residents of the stroke belt were oversampled. Global cognitive status was assessed annually by telephone with the Six-item Screener (SIS) and the diagnosis of incident HF was validated by physicians using medical records and standard clinical criteria. Participants who were hospitalized for incident HF from 2004 until 2016 with a SIS completed &gt; 1 month but &lt; 18 months before the index hospitalization were included. After determining the prevalence of cognitive impairment among this cohort, we identified which of their baseline characteristics were independently associated with cognitive impairment using multivariable logistic regression. We then compared the prevalence of cognitive impairment among adults with incident HF to the prevalence of cognitive impairment among age, sex, and race matched participants without HF, stratifying by 10-year Framingham Coronary Heart Disease Risk Scores (FRS) (&lt;10%, 10-20%, and &gt; 20%). Results: Of the 436 participants with incident HF, 14.9% had cognitive impairment. In an age-adjusted model, older age (OR 1.04 [95% CI 1.01 - 1.08], black race (OR 1.88 [95% 1.08-3.28]), &lt; high school education (OR 1.89 [95% 1.02-3.51]), and anticoagulation (OR 3.01 [95% 1.05 - 8.63]) were independently associated with higher odds of cognitive impairment, whereas female sex (OR 0.54 [95% 0.31 - 0.94]) was associated with lower odds of cognitive impairment. The prevalence of cognitive impairment among participants with incident HF was higher than the prevalence of cognitive impairment among controls with low FRS (9.4%) but was less than the prevalence of cognitive impairment among controls with high FRS (21.9%). Conclusion: The prevalence of cognitive impairment among adults with incident HF was greater than the prevalence of cognitive impairment among matched participants with low CHD risk, but less than the prevalence of cognitive impairment among matched participants with the highest CHD risk. This suggests that the majority of cognitive decline in HF may occur later in the course of the disease. Increased awareness of cognitive impairment among newly diagnosed patients, as well as ways to mitigate cognitive decline in the context of HF management, are warranted.

Body composition measures and cardiovascular risk in high-risk ethnic groups

Cardiovascular disease (CVD) is highly prevalent in Suriname, a middle-income country with predominantly people of African and Asian ancestry. We examined whether the more comprehensive body composition measures determined by bioelectrical impedance analysis (BIA) are superior to the more traditional BMI and waist measures in relation to cardiovascular risk. Data from the cross-sectional Healthy Life in Suriname (HELISUR) study were used to calculate BMI, waist-hip ratio, waist-to-height ratio, and waist circumference. BIA was used to estimate fat percentage, fat-free mass index, and fat-to-fat-free mass ratio. High cardiovascular risk was defined as 1) a 10-year Framingham coronary heart disease risk score ≥10% in African-Surinamese and ≥12% in Asian-Surinamese, and 2) an increased arterial stiffness (pulse wave velocity >10m/s). Using logistic regression analysis, we pre-selected the strongest correlate (i.e. lowest p-value below 0.05) of all body composition items for both outcomes of cardiovascular risk separately, and subsequently, used forward logistic regression modelling to determine whether other measures added value to the initial model with the strongest correlate (-2 log-likelihood (-2LL) of initial model minus-2LL of new model, χ-square statistic >3.841, 1 df). Analyses were adjusted for sex, age and ethnicity. We examined 691 participants (65% women; 48% African-Surinamese) with a mean age of 42 (SD 14) years. Waist circumference was the strongest correlate for high 10-year CVD risk in the total group, in men and African-Surinamese. In Asian-Surinamese, fat-free mass index was the strongest correlate of high 10-year CVD risk. Increased arterial stiffness was most strongly related with waist-to-height ratio in the total group and in African-Surinamese, and with BMI in men. None of the measures were significantly associated in women (for both outcomes) and Asian-Surinamese (for increased arterial stiffness). Forward selection showed that only BMI added value next to waist-to-height ratio in the total group in relation to increased arterial stiffness. Waist measures, in particular waist circumference and waist-to-height ratio, and BMI should be used in African and Asian-Surinamese to identify who is at increased cardiovascular risk. Overall, we found little advantage in using BIA measures rather than simple anthropometric measures.

Association Between Age at Menarche and Risk Factors for Cardiovascular Diseases in Korean Women: The 2010 to 2013 Korea National Health and Nutrition Examination Survey.

Early menarche is strongly associated with adulthood obesity; however, the relationship between age at menarche and cardiovascular disease (CVD) in Korean women remains poorly understood. Here, we investigated the association between early menarche and risk factors for developing CVD during adulthood using a nationwide population database.In total, 12,336 women (weighted n = 17,483,406; weighted age, 45.7 years) who participated in the Korean National Health and Nutrition Examination Survey 2010 to 2013 were included in this study. Participants were scored using the National Cholesterol Education Program Adult Treatment Panel III criteria for metabolic syndrome. Risk of CVD was estimated using the 10-year Framingham Coronary Heart Disease Risk Point Scale (10-year FRS).Early menarche (≤11 years) was reported in 5.2% (weighted n = 917,493) of subjects. The weighted prevalences of metabolic syndrome and ≥20% 10-year FRS were 23.6% [95% confidence interval (95% CI), 22.7–24.6] and 7.7% (7.1–8.3), respectively. Women with early menarche reported a significantly higher body mass index and waist circumference, along with a higher prevalence of hypertension, diabetes, and metabolic syndrome than those with later menarche (≥13 years). Furthermore, the prevalence of women with a ≥10% or ≥20% 10-year FRS was higher in those with early menarche than in other groups after adjusting for age, smoking, education level, and menstruation. Logistic regression analyses controlling for these and other confounding factors revealed odds ratios of 2.29 (95% CI = 1.25–4.19) and 1.78 (0.96–3.30) for ≥10% and ≥20% 10-year FRS in women with early menarche, respectively, compared with those in the latest menarche group (≥17 years).Taken together, this nationwide study revealed that women with early menarche are at increased risks of metabolic syndrome and CVD. Early menarche may therefore represent an important marker for early preventive interventions.

Six-month changes in ideal cardiovascular health vs. Framingham 10-year coronary heart disease risk among young adults enrolled in a weight loss intervention

The Framingham Risk equation uses sex, age, smoking, total cholesterol, high-density lipoprotein (HDL) cholesterol and systolic blood pressure to predict 10-year risk of coronary heart disease (FR-10). The American Heart Association's Ideal Cardiovascular Health (IDEAL) score uses smoking, total cholesterol, fasting glucose, blood pressure, body mass index (BMI), diet, and physical activity to encourage a healthy cardiovascular phenotype. This study aimed to compare 6-month changes in the FR-10 vs. IDEAL score among young adults with BMI ≥25 to <40kg/m2 enrolled in a behavioral weight loss intervention at the University of Pittsburgh (2010–12). Medians [25th, 75th percentiles] are reported. Weight decreased by 8kg [−12, −4] among 335 participants. Of 7 possible points, IDEAL score was 4 [3, 4] at baseline, improved (i.e., increased) by 1 [0, 2] over 6months, and improved in 64.2% and worsened in 6.6% of participants (p<0.001). IDEAL classification of BMI, physical activity, total cholesterol, blood pressure and glucose improved (all p<0.001), but not of smoking or diet (both p≥0.05). FR-10 was <1% at baseline for 88.1% of participants and changed in few participants (improved, i.e. decreased, in 7.5%, worsened in 1.8%, p<0.001). Among young adults with overweight or obesity enrolled in a weight loss intervention, IDEAL detected positive changes in a majority of participants while the FR-10 did not. These findings suggest that IDEAL score may be more sensitive to positive cardiovascular health changes resulting from a behavioral intervention in this population.

Statin Underuse and Low Prevalence of LDL-C Control Among U.S. Adults at High Risk of Coronary Heart Disease

BackgroundStatins reduce the risk of coronary heart disease (CHD) in individuals with a history of CHD or risk equivalents. A 10-year CHD risk >20% is considered a risk equivalent but is frequently not detected. Statin use and low-density lipoprotein cholesterol (LDL-C) control were examined among participants with CHD or risk equivalents in the nationwide Reasons for Geographic and Racial Differences in Stroke study (n=8812). MethodsParticipants were categorized into 4 mutually exclusive groups: (1) history of CHD (n=4025); (2) no history of CHD but with a history of stroke and/or abdominal aortic aneurysm (AAA) (n=946); (3) no history of CHD or stroke/AAA but with diabetes mellitus (n=3134); or (4) no history of the conditions in (1) through (3) but with 10-year Framingham CHD risk score (FRS) >20% calculated using the third Adult Treatment Panel point scoring system (n=707). ResultsStatins were used by 58.4% of those in the CHD group and 41.7%, 40.4% and 20.1% of those in the stroke/AAA, diabetes mellitus and FRS >20% groups, respectively. Among those taking statins, 65.1% had LDL-C <100mg/dL, with no difference between the CHD, stroke/AAA, or diabetes mellitus groups. However, compared with those in the CHD group, LDL-C <100mg/dL was less common among participants in the FRS >20% group (multivariable adjusted prevalence ratio: 0.72; 95% confidence interval: 0.62-0.85). Results were similar using the 2013 American College of Cardiology/American Heart Association cholesterol treatment guideline. ConclusionsThese data suggest that many people with high CHD risk, especially those with an FRS >20%, do not receive guideline-concordant lipid-lowering therapy and do not achieve an LDL-C <100mg/dL.

The inter-arm difference in systolic blood pressure is a novel risk marker for subclinical atherosclerosis in patients with type 2 diabetes

Recent studies have suggested that the inter-arm blood pressure difference (IAD) is associated with cardiovascular events and mortality. The aim of this study was to assess whether the IAD could be a marker for subclinical atherosclerosis in patients with type 2 diabetes who are at high risk of cardiovascular disease (CVD). In a cross-sectional retrospective study of 206 Japanese patients with type 2 diabetes aged 49-76 years, we examined the correlation of the IAD with the carotid intima-media thickness (IMT), ankle-brachial index (ABI) or cardio ankle vascular index (CAVI). The IAD was positively correlated with the maximum IMT (r=0.266, P<0.0001), mean IMT (r=0.209, P=0.00726) or CAVI (r=0.240, P=0.0005). The IAD was higher in patients with CVD than in those without (P=0.0020). A multiple linear regression analysis demonstrated that the IAD was an independent determinant of maximum IMT (β=0.169, P=0.0167), mean IMT (β=0.178, P=0.0153), ABI (β=-0.222, P=0.0033) or CAVI (β=0.213, P=0.0011) after adjusting for known risk factors. The area under the receiver operating characteristic curve (AUC) of the IAD as a predictor of subclinical atherosclerosis was similar to the AUC of the Framingham 10-year coronary heart disease risk score. In conclusion, the IAD could be a novel risk marker for subclinical atherosclerosis in patients with type 2 diabetes.

Reduction in cardiovascular risk using a proactive multifactorial intervention is consistent among patients residing in Pacific Asian and non-Pacific Asian regions: a CRUCIAL trial subanalysis

BackgroundFew trials have compared different approaches to cardiovascular disease prevention among Pacific Asian (PA) populations. The Cluster Randomized Usual Care versus Caduet Investigation Assessing Long-term-risk (CRUCIAL) trial demonstrated that a proactive multifactorial intervention (PMI) approach (based on single-pill amlodipine/atorvastatin) resulted in a greater reduction in calculated Framingham 10-year coronary heart disease (CHD) risk compared with usual care (UC) among hypertensive patients with additional risk factors. One-third of CRUCIAL patients resided in the PA region. The aim of this subanalysis was to compare two approaches to cardiovascular risk factor management (PMI versus UC) among patients residing in PA and non-PA regions.MethodsThis subanalysis of the CRUCIAL trial compared treatment-related changes in calculated CHD risk among patients residing in PA and non-PA regions. Sensitivity analyses were conducted among men and women and those with and without diabetes.ResultsOverall, 448 patients (31.6%) resided in the PA region and 969 patients (68.4%) resided in non-PA regions. The PMI approach was more effective in reducing calculated CHD risk versus UC in both PA (−37.1% versus −3.5%; P<0.001) and non-PA regions (−31.1% versus −4.2%; P<0.001); region interaction P=0.131. PA patients had slightly greater reductions in total cholesterol compared with non-PA patients. PA patients without diabetes had slightly greater reductions in CHD risk compared with non-PA patients. Treatment effects were similar in men and women and those with diabetes.ConclusionThe PMI approach was more effective in reducing calculated Framingham 10-year CHD risk compared with UC among men and women with and without diabetes residing in the PA and non-PA region.

Assessing 10-year coronary heart disease risk in people with Type 2 diabetes mellitus: Framingham versus United Kingdom Prospective Diabetes Study

Aims: Previous studies have suggested that the Framingham coronary heart disease risk prediction equation underestimates risk among people with Type 2 diabetes. We compared the 10-year absolute risks of coronary heart disease (CHD) using a Framingham equation and a United Kingdom Prospective Diabetes Study (UKPDS) equation in adults with Type 2 diabetes. Methods: Participants were from a cross-sectional survey of a randomly selected population. There were 461 people with newly (n = 132) or previously diagnosed (n = 329) diabetes aged 35 to 74 years with no past history of cardiovascular disease or nephropathy. We examined predicted 10-year CHD risk by age, gender, and newly or previously diagnosed diabetes. Results: Overall the mean 10-year CHD risks predicted by the two equations were similar. Among men, the UKPDS and Framingham scores were almost identical below 60 years of age but at older ages, the UKPDS score was 4% - 11% higher than Framingham. For women, the Framingham score was higher than the UKPDS score between ages 40 and 65 years, but the UKPDS score was about 4% - 5% higher for women aged 70 years and over. The UKPDS equation tended to give higher risk estimates in people with a predicted 10-year Framingham CHD risk above 15%. Conclusion: Framingham CHD risk scores tended to be lower than UKPDS scores primarily in people above standard thresholds for drug treatment, so the clinical impact of underestimating risk is likely to be limited. Moreover, the UKPDS equation predicted lower risks than Framingham for women and newly diagnosed diabetes at otherwise low to moderate CHD risk, which could result in later initiation of therapy in these groups if the UKPDS score was used instead of the Framingham score.

Refractory Hypertension

See related article, p 451–458 Calhoun et al1 in this edition of the journal report on an important clinical phenotype: refractory hypertension. They provide important information on the prevalence, risk factors, and comorbidities for refractory hypertension in a large observational study, including adults from across the United States.2 They note that 0.5% of the patients receiving antihypertensive treatment and 3.6% of the individuals with resistant hypertension had refractory hypertension. These observations are of great importance and provide key evidence that true antihypertensive treatment failure is uncommon. Moreover, the observations also help us appreciate the paradox that with an increasing number of medications needed to treat hypertension, there is an association with greater proclivity for refractory hypertension. In their study, they note that patients of African descent, and those with albuminuria and diabetes mellitus, were more likely to have refractory hypertension, even after multivariable adjustment. Moreover, individuals with refractory hypertension had a much higher 10-year Framingham coronary heart disease and stroke risk score than those without. This observation underscores the importance of hypertension as a major risk factor for promoting cardiovascular disease. So what is the cause of refractory hypertension? …

Abstract 18274: Under Use of Statins and LDL-C Control Among People With a Framingham 10-Year Coronary Heart Disease Risk &gt; 20%

Statins reduce the incidence of coronary heart disease (CHD) in individuals with a history of CHD or risk equivalents. A 10-year CHD risk &gt;20% is considered a CHD risk equivalent but is frequently not estimated. We studied the use of statins and control of LDL-C among participants with a history of CHD or CHD risk equivalents in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study (n=30,239) The 8,812 participants with CHD or risk equivalents were categorized into four mutually exclusive groups: (1) history of CHD, (2) no history of CHD but with a history of stroke and/or aortic aneurysm, (3) no history of CHD, stroke or aortic aneurysm but with diabetes mellitus, or (4) no history of the conditions listed in (1) through (3) but with a Framingham 10-year CHD risk &gt; 20% at baseline. Lipids were measured after an overnight fast, LDL-C was calculated using the Friedewald equation, and statin use was assessed through pill bottle review during an in-home study visit. The mean age of study participants was 65 years (SD=9), 45% were women and 46% were black. In fully adjusted models, compared to those with a history of CHD, the use of statins was statistically significantly lower among people with a history of stroke/aortic aneurysm, history of diabetes, and especially 10-year CHD risk &gt; 20% (Table). Among high risk participants taking statins, the prevalence of LDL-C &lt; 100 mg/dL was similar for those with a history of CHD, a history of stroke/aortic aneurysm and diabetes, but participants with a 10-year CHD risk &gt; 20% were less likely to have an LDL-C &lt; 100 mg/dL. These data suggest many people with high CHD risk, especially those with a FRS &gt;20%, were not receiving guideline-concordant lipid-lowering therapy and quality improvement efforts should focus on this group.

Awareness, Treatment, and Control of LDL Cholesterol Are Lower Among U.S. Adults With Undiagnosed Diabetes Versus Diagnosed Diabetes

OBJECTIVEDiabetes is often undiagnosed, resulting in incorrect risk stratification for lipid-lowering therapy. We conducted a cross-sectional analysis of the National Health and Nutrition Examination Survey (NHANES) 2005–2010 to determine the prevalence, awareness, treatment, and control of elevated LDL cholesterol (LDL-C) among U.S. adults with undiagnosed diabetes.RESEARCH DESIGN AND METHODSFasting NHANES participants 20 years of age or older who had 10-year Framingham coronary heart disease (CHD) risk scores <20% and were free of CHD or other CHD risk equivalents (n = 5,528) were categorized as having normal glucose, impaired fasting glucose, undiagnosed diabetes, or diagnosed diabetes. High LDL-C was defined by the 2004 Adult Treatment Panel (ATP) III guidelines.RESULTSThe prevalence of diagnosed and of undiagnosed diabetes was 8 and 4%, respectively. Mean LDL-C was 102 ± 2 mg/dL among those with diagnosed diabetes and 117 ± 3 mg/dL for those with undiagnosed diabetes (P < 0.001). The prevalence of high LDL-C was similar among individuals with undiagnosed (81%) and diagnosed (77%) diabetes. Among individuals with undiagnosed diabetes and high LDL-C, 38% were aware, 27% were treated, and 16% met the ATP III LDL-C goal for diabetes. In contrast, among individuals with diagnosed diabetes and high LDL-C, 70% were aware, 61% were treated, and 36% met the ATP III goal. Subjects with undiagnosed diabetes remained less likely to have controlled LDL-C after multivariable adjustment (prevalence ratio, 0.42; 95% CI, 0.23–0.80).CONCLUSIONSImproved screening for diabetes and reducing the prevalence of undiagnosed diabetes may identify individuals requiring more intensive LDL-C reduction.

Cardiovascular risk factors associated with the metabolic syndrome are more prevalent in people reporting chronic pain: Results from a cross-sectional general population study

To explore whether chronic pain is associated with cardiovascular risk factors and identify whether increased distribution or intensity of pain is associated with cardiovascular risk, participants in Generation Scotland: The Scottish Family Health study completed pain questionnaires recording the following: presence of chronic pain, distribution of pain, and intensity of chronic pain. Blood pressure, lipids, blood glucose, smoking history, waist–hip ratio, and body mass index were recorded; Framingham 10-year coronary heart disease (CHD) risk scores were calculated and a diagnosis of metabolic syndrome derived. Associations between chronic pain and cardiovascular risk were explored. Of 13,328 participants, 1100 (8.3%) had high CHD risk. Chronic pain was reported by 5209 (39%), 1294 (9.7%) reported widespread chronic pain, and 707 (5.3%) reported high-intensity chronic pain. In age- and gender-adjusted analyses, chronic pain was associated with elevated CHD risk scores (odds ratio 1.11, 95% confidence interval 1.01–1.23) and the metabolic syndrome (odds ratio 1.42, 95% confidence interval 1.24–1.62). Multivariate analyses identified dyslipidaemia, age, gender, smoking, obesity, and high waist–hip ratio as independently associated with chronic pain. Within the chronic pain subgroup, widespread pain did not confer any additional cardiovascular disease risk. However, cardiovascular disease risk factors contributing to metabolic syndrome were more prevalent in those reporting high-intensity chronic pain. This large population-based study has demonstrated that chronic pain, and in particular high-intensity chronic pain, is associated with an increased prevalence of cardiovascular risk factors and metabolic syndrome. The 10-year CHD risk score and metabolic syndrome correlate well with increased pain intensity, but not with widespread pain.

Evaluation of a community intervention program in Japan using Framingham risk score and estimated 10-year coronary heart disease risk as outcome variables: a non-randomized controlled trial

BackgroundCommunity-based programs are being widely adopted in the struggle to prevent cardiovascular diseases. No study has been conducted in Japan to evaluate the effects of a community-based health promotion program by using the Framingham risk score and 10-year CHD risk as outcome variables. The aim of the present study was to assess the effects of a program involving 6-month intervention and 18-month follow-up using such outcomes.MethodsParticipants (n = 1,983, 39.5% women, mean age 63.4 years) were selected for the study in 2008. Of these 1,983, 347 (42.4% women) subjects received the 6-month intervention. The intervention included individual counseling and group sessions, among others. After 18 months, 1,278 participants (intervention group: 238, control group: 1,040) were followed up. Changes in the Framingham risk score and 10-year coronary heart disease (CHD) risk were evaluated. ANCOVA and multiple logistic models adjusted for baseline value, age, sex and intervention times were used.ResultsThe results showed that the differences in the Framingham risk score and mean 10-year CHD risk were significant in the intervention group compared with the control group after 6-month follow-up (-0.46 and -1.12, respectively) and were also significant after 18-month follow-up (-0.39 and -0.85, respectively). The proportion of those with intermediate 10-year CHD risk (> = 10%) was significantly lower at 6 months (OR 0.30, 95% CI 0.12-0.74) and at 18 months (OR 0.41, 95% CI 0.19-0.92).ConclusionsThe six-month intervention program effectively decreased estimated 10-year CHD risk and the effects were still present at 18-month follow-up.Trial registrationUMIN-CTR: UMIN000008163

The QT Interval Could be a Marker of Subclinical Atherosclerosis in Patients with Type 2 Diabetes

Several studies have shown that prolongation of QT interval predicts the risks of all-cause and cardiovascular mortality. Moreover, a close association was reported between prolongations of QT interval and pulse wave velocity (PWV) in general population without preexisting cardiovascular disease. The aim of this study was to evaluate the relationship between QT interval and PWV in patients with type 2 diabetes without preexisting cardiovascular disease. In a cross-sectional study of 251 Japanese patients with type 2 diabetes, we examined the correlation of the heart rate-corrected QT interval duration (QTc) with PWV or other various parameters, including age, duration of diabetes, body mass index, systolic blood pressure, hemoglobin A1c, serum cholesterol, creatinine, uric acid, potassium, severity of diabetic nephropathy or retinopathy and current treatment of diabetes. The QTc correlated positively with PWV (r=0.268, p<0.0001). Multiple regression analysis demonstrated that the QTc was independently correlated with PWV (β=0.155, p=0.0119), after adjustment for known risk factors. According to the receiver operator characteristic analyses (ROC), the area under the ROC curve (AUC) of QTc and the Framingham 10-year coronary heart disease risk score (FRS) for arterial stiffness were 0.69 and 0.64, respectively. The AUC of QTc for arterial stiffness was similar to that of FRS for artificial stiffness (p=0.6532). In conclusion, the QT interval could be a marker of subclinical atherosclerosis in patients with type 2 diabetes.

Proactive Cardiovascular Risk Management versus Usual Care in Patients with and without Diabetes Mellitus: CRUCIAL Trial Subanalysis

Patients with diabetes mellitus (DM) and additional cardiovascular (CV) risk factors are at very high risk for future CV events. This study investigated the efficacy and safety of a proactive, multifactorial CV risk factor–management strategy based on single–pill amlodipine/atorvastatin (SPAA) versus continuing physicians' usual care (UC) over 52 weeks in patients with and without DM. Patients with hypertension and ≥ 3 additional CV risk factors from the Cluster Randomized Usual Care vs Caduet Investigation Assessing Long–Term–Risk (CRUCIAL) trial–an open–label, cluster–randomized trial conducted in 19 countries–were enrolled and randomized to receive proactive intervention (based on SPAA 5/10 to 10/20 mg) or UC (based on investigators' best clinical judgment). Patients were analyzed according to baseline DM status. Six hundred patients had DM. Patients with DM in the SPAA and UC arms had mean ages of 61.8 and 61.5 years, respectively, and an absolute coronary heart disease (CHD) risk of 25.2% and 21.5%, respectively. Among non–DM patients, mean ages were 58.6 and 59.5 years, respectively, and CHD risk was 16.0% vs 15.7%, respectively. Least–squares mean treatment differences in percentage change from baseline in calculated 10-year Framingham CHD risk were −26.3% vs −27.3% among DM and non–DM patients (adjusted for respective baseline values) (both P < 0.0001). Among DM and non–DM patients, adverse events were reported in 52.8% versus 45.6% in the SPAA and 49.6% versus 41.6% in the UC arms, respectively. This global risk–management approach, simultaneously targeting blood pressure and lipids, was more effective for reducing calculated 10-year Framingham CHD risk than UC in patients with DM. While blood pressure changes were of smaller magnitude among patients with DM, this strategy reduced overall risk to an extent comparable with that observed in non–DM patients. Further studies are thus warranted to study this proactive risk factor intervention on CV or mortality endpoints in patients with and without DM.

Increased plasma levels of retinol-binding protein 4 with visceral obesity is associated with cardiovascular risk factors.

Aims/Introduction: Visceral obesity has been suggested to be an independent risk factor for cardiovascular disease (CVD); the role of adipokines in the risk for CVD is less clear. Aim of this study was to investigate the relationship between parameters of visceral obesity and index of CVD risk factors. A cross-sectional analysis of healthy males (n = 116) and females (n = 175) for evaluation of clinical, laboratory and anthropometric parameters were undertaken. Abdominal subcutaneous (SAT) and visceral adipose tissues (VAT) were measured by computed tomography. Adipokines, including retinol-binding protein 4 (RBP4) and adiponectin, were determined. The risk for CVD was estimated using the 10-year Framingham Coronary Heart Disease Risk Point scale (Framingham score). The Framingham score was increased in subjects with metabolic syndrome, and significantly increased with various indices of obesity, traditional risk factors of CVD, C-reactive protein (CRP) and RBP4, but decreased with adiponectin. With multiple linear regression analysis, the Framingham score independently associated with age, smoking status, body mass index, triglyceride and RBP4. The magnitude of the Framingham score showed a linear trend of increase with CRP, VAT and RBP4 (all P < 0.001), but of decrease with SAT and adiponectin (all P < 0.05) at stratified levels of obesity. RBP4 is increased with visceral fat accumulation and associated with CVD risk factors independent of obesity or traditional risk factors. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2012.00213.x, 2012).

Association of Catalytic Iron With Cardiovascular Disease

The ability of iron to cycle reversibly between its ferrous and ferric oxidation states is essential for the biological functions of iron but may contribute to vascular injury through the generation of powerful oxidant species. We examined the association between chemical forms of iron that can participate in redox cycling, often referred to as "catalytic" or "labile" iron, and cardiovascular disease (CVD). In our cross-sectional study of 496 participants, 85 had CVD. Serum catalytic iron was measured using the bleomycin-detectable iron assay that detects biologically active iron. The odds of existing CVD for subjects in the upper third of catalytic iron were 10 times that of subjects with lower catalytic iron in unadjusted analyses. The association was decreased by 1/2 by age adjustment, but little additional attenuation occurred after adjusting for age, Framingham Risk Score, estimated glomerular filtration rate, hypertension status, high-density lipoprotein cholesterol, and systolic blood pressure, with the association remaining strong and significant (odds ratio 3.8, 95% confidence interval 1.4 to 10.1). In conclusion, we provide preliminary evidence for a strong detrimental association between high serum catalytic iron and CVD even after adjusting for several co-morbid conditions; however, broader prospective studies are needed to confirm these findings, which would support therapeutic trials to assess the beneficial effects of iron chelators on CVD.

Proactive multiple cardiovascular risk factor management compared with usual care in patients with hypertension and additional risk factors: the CRUCIAL trial

Objective:To investigate whether a proactive multifactorial risk factor intervention strategy using single-pill amlodipine/atorvastatin (5/10, 10/10 mg) in addition to other antihypertensive and lipid-lowering therapy, as required, resulted in greater reduction in calculated Framingham 10-year coronary heart disease (CHD) risk compared with usual care (UC) after 52-weeks treatment.Research design and methods:Prospective, multinational, open-label, cluster randomized trial, with the investigator as the unit of randomization. Eligible hypertensive patients were 35–79 years of age, with ≥3 additional cardiovascular risk factors, but no history of CHD and baseline total cholesterol (TC) ≤6.5 mmol/l.Clinical trial registration:Trial registration: ClinicalTrials.gov identifier: NCT00407537.Main outcome measure:The primary endpoint was calculated Framingham 10-year CHD risk at 52 weeks.Results:Of the 140 randomized sites, 136 sites contributed 1461 patients. Mean baseline age and low-density lipoprotein cholesterol (LDL-C) were comparable between treatment arms. Mean baseline BP (150.3/89.7 vs. 144.3/86.5 mmHg) and Framingham CHD risk (20.0 vs. 18.1%) were higher in the proactive intervention versus the UC arm (p < 0.002 for both). At week 52, mean CHD risk was 12.5% in the proactive intervention arm and 16.3% in the UC arm (p < 0.001). The difference, observed at weeks 16 and 52, was primarily driven by significant differences in systolic BP and in TC between the two arms. Overall, adverse events (AEs) were reported in 48.8% and 44.0% of patients in the proactive intervention and the UC arm, respectively. Although there were differences in the incidence of AEs between the treatment arms, the AE profile in the proactive intervention arm was consistent with previous safety experience for this medication.Conclusions:A proactive multifactorial risk factor intervention strategy that simultaneously treated both BP and cholesterol regardless of individual risk factors per se, is more effective in reducing calculated Framingham 10-year CHD risk than UC in patients with hypertension and additional risk factors.