The role of coronary artery calcium (CAC) testing for guiding preventive strategies among women at low cardiovascular disease (CVD) risk based on the American College of Cardiology and American Heart ...Association CVD prevention guidelines is unclear.
To assess the potential utility of CAC testing for CVD risk estimation and stratification among low-risk women.
Women with 10-year atherosclerotic CVD (ASCVD) risk lower than 7.5% from 5 large population-based cohorts: the Dallas Heart Study (United States), the Framingham Heart Study (United States), the Heinz Nixdorf Recall study (Germany), the Multi-Ethnic Study of Atherosclerosis (United States), and the Rotterdam Study (the Netherlands). The 5 cohorts were selected based on the availability of CAC data in a sizable group of low-risk women from the general population together with the long detailed follow-up data. Across the cohorts, events were assessed from the date of CAC scan (performed from 1998 through 2006) until January 1, 2012; January 1, 2014; or March 6, 2015. Fixed-effects meta-analysis was conducted to combine the results of the 5 studies.
CAC score by computed tomography.
Main outcome was incident ASCVD, including nonfatal myocardial infarction, coronary heart disease (CHD) death, and stroke. Association of CAC with ASCVD was examined using Cox proportional hazards models. To assess whether CAC was associated with improved ASCVD risk predictions beyond the traditional risk factors, the C statistic and the continuous net reclassification improvement (cNRI) index were calculated.
Among 6739 women with low ASCVD risk from the 5 studies, mean age ranged from 44 to 63 years and CAC was present in 36.1%. Across the cohorts, median follow-up ranged from 7.0 to 11.6 years. A total of 165 ASCVD events occurred (64 nonfatal myocardial infarctions, 29 CHD deaths, and 72 strokes), with the ASCVD incidence rates ranging from 1.5 to 6.0 per 1000 person-years. Compared with the absence of CAC (CAC = 0), presence of CAC (CAC >0) was associated with an increased risk of ASCVD (incidence rates per 1000 person-years, 1.41 for CAC absence vs 4.33 for CAC presence; difference, 2.92 95% CI, 2.02-3.83; multivariable-adjusted hazard ratio, 2.04 95% CI, 1.44-2.90). The addition of CAC to traditional risk factors improved the C statistic from 0.73 (95% CI, 0.69-0.77) to 0.77 (95% CI, 0.74-0.81) and provided a cNRI of 0.20 (95% CI, 0.09-0.31) for ASCVD prediction.
Among women at low ASCVD risk, CAC was present in approximately one-third and was associated with an increased risk of ASCVD and modest improvement in prognostic accuracy compared with traditional risk factors. Further research is needed to assess the clinical utility and cost-effectiveness of this additional accuracy.
Left ventricular (LV) mass and geometry are associated with risk of cardiovascular disease (CVD). We sought to determine whether LV mass and geometry contribute to risk prediction for CVD in adults ...aged ≥65 years of the Cardiovascular Health Study. We indexed LV mass to body size, denoted as LV mass index (echo-LVMI), and we defined LV geometry as normal, concentric remodeling, and eccentric or concentric LV hypertrophy. We added echo-LVMI and LV geometry to separate 10-year risk prediction models containing traditional risk factors and determined the net reclassification improvement (NRI) for incident coronary heart disease (CHD), CVD (CHD, heart failure HF, and stroke), and HF alone. Over 10 years of follow-up in 2,577 participants (64% women, 15% black, mean age 72 years) for CHD and CVD, the adjusted hazards ratios for a 1-SD higher echo-LVMI were 1.25 (95% CI 1.14 to 1.37), 1.24 (1.15 to 1.33), and 1.51 (1.40 to 1.62), respectively. Addition of echo-LVMI to the standard model for CHD resulted in an event NRI of −0.011 (95% CI −0.037 to 0.028) and nonevent NRI of 0.034 (95% CI 0.008 to 0.076). Addition of echo-LVMI and LV geometry to the standard model for CVD resulted in an event NRI of 0.013 (95% CI −0.0335 to 0.0311) and a nonevent NRI of 0.043 (95% CI 0.011 to 0.09). The nonevent NRI was also significant with addition of echo-LVMI for HF risk prediction (0.10, 95% CI 0.057 to 0.16). In conclusion, in adults aged ≥65 years, echo-LVMI improved risk prediction for CHD, CVD, and HF, driven primarily by improved reclassification of nonevents.
This study sought to determine if coronary artery calcium (CAC) is associated with incident noncardiovascular disease.
CAC is considered a measure of vascular aging, associated with increased risk of ...cardiovascular and all-cause mortality. The relationship with noncardiovascular disease is not well defined.
A total of 6,814 participants from 6 MESA (Multi-Ethnic Study of Atherosclerosis) field centers were followed for a median of 10.2 years. Modified Cox proportional hazards ratios accounting for the competing risk of fatal coronary heart disease were calculated for new diagnoses of cancer, pneumonia, chronic obstructive pulmonary disease (COPD), chronic kidney disease (CKD), deep vein thrombosis/pulmonary embolism, hip fracture, and dementia. Analyses were adjusted for age; sex; race; socioeconomic status; health insurance status; body mass index; physical activity; diet; tobacco use; number of medications used; systolic and diastolic blood pressure; total and high-density lipoprotein cholesterol; antihypertensive, aspirin, and cholesterol medication; and diabetes. The outcome was first incident noncardiovascular disease diagnosis.
Compared with those with CAC = 0, those with CAC >400 had an increased hazard of cancer (hazard ratio HR: 1.53; 95% confidence interval CI: 1.18 to 1.99), CKD (HR: 1.70; 95% CI: 1.21 to 2.39), pneumonia (HR: 1.97; 95% CI: 1.37 to 2.82), COPD (HR: 2.71; 95% CI: 1.60 to 4.57), and hip fracture (HR: 4.29; 95% CI: 1.47 to 12.50). CAC >400 was not associated with dementia or deep vein thrombosis/pulmonary embolism. Those with CAC = 0 had decreased risk of cancer (HR: 0.76; 95% CI: 0.63 to 0.92), CKD (HR: 0.77; 95% CI: 0.60 to 0.98), COPD (HR: 0.61; 95% CI: 0.40 to 0.91), and hip fracture (HR: 0.31; 95% CI: 0.14 to 0.70) compared to those with CAC >0. CAC = 0 was not associated with less pneumonia, dementia, or deep vein thrombosis/pulmonary embolism. The results were attenuated, but remained significant, after removing participants developing interim nonfatal coronary heart disease.
Participants with elevated CAC were at increased risk of cancer, CKD, COPD, and hip fractures. Those with CAC = 0 are less likely to develop common age-related comorbid conditions, and represent a unique population of "healthy agers."
Statins form the pharmacologic cornerstone of the primary and secondary prevention of atherosclerotic cardiovascular disease. In addition to beneficial cardiovascular effects, statins seem to have ...multiple non-cardiovascular effects. Although early concerns about statin induced hepatotoxicity and cancer have subsided owing to reassuring evidence, two of the most common concerns that clinicians have are myopathy and diabetes. Randomized controlled trials suggest that statins are associated with a modest increase in the risk of myositis but not the risk of myalgia. Severe myopathy (rhabdomyolysis) is rare and often linked to a statin regimen that is no longer recommended (simvastatin 80 mg). Randomized controlled trials and meta-analyses suggest an increase in the risk of diabetes with statins, particularly with higher intensity regimens in people with two or more components of the metabolic syndrome. Other non-cardiovascular effects covered in this review are contrast induced nephropathy, cognition, cataracts, erectile dysfunction, and venous thromboembolism. Currently, systematic reviews and clinical practice guidelines indicate that the cardiovascular benefits of statins generally outweigh non-cardiovascular harms in patients above a certain threshold of cardiovascular risk. Literature is also accumulating on the potential non-cardiovascular benefits of statins, which could lead to novel applications of this class of drug in the future.
When present clinically, cardiac involvement in systemic sclerosis (SSc) is a major risk factor for death. It is therefore vitally important to understand the epidemiology, screening, diagnosis, and ...treatment of the cardiac manifestations of SSc.
The epidemiology of cardiac involvement in SSc has been the subject of several recent studies. Most importantly, the prevalence of overt left ventricular (LV) systolic dysfunction and its associated risk factors have been defined, and patients with diffuse cutaneous SSc appear to be most susceptible to direct cardiac involvement. From a diagnostic and screening standpoint, tissue Doppler echocardiography and natriuretic peptides have provided fresh insight into subclinical cardiac dysfunction in SSc. Newer techniques, such as speckle-tracking echocardiography, diffuse myocardial fibrosis imaging, and absolute myocardial perfusion imaging, are poised to further advance our knowledge. Lastly, there is now consistent observational data to suggest a central role for calcium channel blockers in the treatment of microvascular ischemia and prevention of overt LV systolic dysfunction, although randomized controlled trials are lacking.
Recent studies have improved our understanding of cardiac involvement in SSc. Nevertheless, key questions regarding screening, diagnosis, and treatment remain. Novel diagnostic techniques and multicenter studies should yield important new data, which will hopefully ultimately result in improved outcomes.
To determine the frequency, associated clinical factors, and prognostic significance of left ventricular (LV) diastolic dysfunction in systemic sclerosis (SSc).
We studied 153 consecutive patients ...with SSc and divided the study sample into those with and without LV diastolic dysfunction using established age-based normal cut-offs for lateral tissue Doppler early mitral annular (E') velocity, a marker of impaired relaxation and diastolic dysfunction. We compared clinical characteristics, laboratory tests, pulmonary function tests, and echocardiographic data between those with and without LV diastolic dysfunction. We used multivariable linear regression analyses to determine the factors most associated with lateral tissue Doppler E' velocity. We also performed multivariable Cox regression analyses to determine whether or not tissue Doppler E' velocity was independently associated with mortality.
LV diastolic dysfunction was present in 23% of the subjects, whereas LV systolic dysfunction was present in 5.2% of subjects. Factors independently associated with LV diastolic dysfunction on multivariable analysis included SSc disease duration, age, coronary artery disease, and systemic hypertension. During a mean follow-up of 1.9±1.3 years, LV diastolic dysfunction was independently associated with increased risk of death (hazard ratio HR 3.2, 95% confidence interval CI 1.1-9.5, p=0.034 per each standard deviation decrease in tissue Doppler E' velocity).
LV diastolic dysfunction in SSc is independently associated with disease duration and is a marker of increased risk of death.
Individuals with electrocardiographically determined left ventricular hypertrophy (ECG LVH) are at risk of multiple cardiovascular disease (CVD) outcomes simultaneously. The study sought to ...characterise the competing incidences for subtypes of first CVD events or non-CVD death in those with and without ECG LVH.
Participants in the Atherosclerosis Risk in Communities (ARIC) Study were included. ECG LVH was defined according to Sokolow-Lyon criteria. Competing Cox models were used to compare hazards for diverse outcomes within groups (e.g., among those with ECG LVH) and for a given event between groups (ECG LVH vs. no ECG LVH).
After 15 years, men with ECG LVH at baseline (N=383) had a cumulative incidence of first CVD events and non-CVD deaths of 29.2% and 6.1%, respectively (HR 4.86; 95% CI 3.04 to 7.77). In men without ECG LVH (N=6576) the incidence of any first CVD event and non-CVD death was 18.9% and 6.9%, respectively (HR 2.67; 2.39 to 2.98). Similar associations were observed in women (N=381 with and N=8187 without ECG LVH). Coronary heart disease (CHD) was the most common first event in men with ECG LVH (15.0%) and heart failure was the most common first event in women with ECG LVH (10.5%). After adjustment for risk factors including systolic blood pressure, any CVD event remained the most likely first event.
Among middle-aged individuals with ECG LVH, the most likely first events are CHD in men and heart failure in women; these results may have implications for preventive approaches.
The aim of this study was to determine the association between cardiovascular health (CVH) in young adulthood and left ventricular (LV) structure and function later in life.
Participants from the ...Coronary Artery Risk Development in Young Adults study, which recruited black and white participants aged 18 to 30 years at baseline, were included; echocardiography was performed at year 25. CVH at year 0 was defined on the basis of blood pressure, total cholesterol, fasting glucose, body mass index, smoking status, diet, and physical activity. Two, 1, or 0 points were assigned to each component for ideal, intermediate, and poor levels of each component. Participants were stratified into CVH groups on the basis of point score: ≤ 8 (poor), 9 to 11 (intermediate), and 12 to 14 (ideal).
The distribution of CVH at year 0 was as follows: poor, n = 264 (9%); intermediate, n = 1,315 (47%); and ideal, n = 1,224 (44%). Individuals with ideal and intermediate CVH at year 0 had significantly lower LV end-diastolic volume and lower LV mass index at year 25. In participants with ideal and intermediate CVH, the multivariate-adjusted odds ratios for diastolic dysfunction at year 25 was 0.52 (95% CI, 0.37-0.73) and 0.63 (95% CI, 0.46-0.83), respectively, compared with participants with poor CVH. Participants with ideal and intermediate CVH had significantly lower odds for LV hypertrophy; the LV mass index was 5.3 to 8.7 g/m(2.7) lower (P < .001 for both) than in participants with poor CVH.
Greater levels of CVH in young adulthood are associated with lower LV mass and lower risk for diastolic dysfunction 25 years later.
The 2013 American College of Cardiology/American Heart Association cardiovascular disease prevention guidelines represent an important step forward in the risk assessment and management of ...atherosclerotic cardiovascular disease in clinical practice. Differentiated risk prediction equations for women and black individuals were developed, and convenient 10-year and lifetime risk assessment tools were provided, facilitating their implementation. Lifestyle modification was portrayed as the foundation of preventive therapy. In addition, based on high-quality evidence from randomized controlled trials, statins were prioritized as the first lipid-lowering pharmacologic treatment, and a shared decision-making model between the physician and the patient was emphasized as a key feature of personalized care. After publication of the guidelines, however, important limitations were also identified. This resulted in a constructive scientific debate yielding valuable insights into potential opportunities to refine recommendations, fill gaps in guidance, and better harmonize recommendations within and outside the United States. The latter point deserves emphasis because when guidelines are in disagreement, this may result in nonaction on the part of professional caregivers or nonadherence by patients. In this review, we discuss the key scientific literature relevant to the guidelines published in the year and a half after their release. We aim to provide cohesive, evidence-based views that may offer pathways forward in cardiovascular disease prevention toward greater consensus and benefit the practice of clinical medicine.
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