Prevalence of Aortic Valve Calcium and the Long-Term Risk of Incident Severe Aortic Stenosis.

BACKGROUND: Aortic valve calcification (AVC) is a principal mechanism underlying aortic stenosis (AS). OBJECTIVES: This study sought to determine the prevalence of AVC and its association with the long-term risk for severe AS. METHODS: Noncontrast cardiac computed tomography was performed among 6,814 participants free of known cardiovascular disease at MESA (Multi-Ethnic Study of Atherosclerosis) visit 1. AVC was quantified using the Agatston method, and normative age-, sex-, and race/ethnicity-specific AVC percentiles were derived. The adjudication of severe AS was performed via chart review of all hospital visits and supplemented with visit 6 echocardiographic data. The association between AVC and long-term incident severe AS was evaluated using multivariable Cox HRs. RESULTS: AVC was present in 913 participants (13.4%). The probability of AVC >0 and AVC scores increased with age and were generally highest among men and White participants. In general, the probability of AVC >0 among women was equivalent to men of the same race/ethnicity who were approximately 10 years younger. Incident adjudicated severe AS occurred in 84 participants over a median follow-up of 16.7 years. Higher AVC scores were exponentially associated with the absolute risk and relative risk of severe AS with adjusted HRs of 12.9 (95% CI: 5.6-29.7), 76.4 (95% CI: 34.3-170.2), and 380.9 (95% CI: 169.7-855.0) for AVC groups 1 to 99, 100 to 299, and ≥300 compared with AVC = 0. CONCLUSIONS: The probability of AVC >0 varied significantly by age, sex, and race/ethnicity. The risk of severe AS was exponentially higher with higher AVC scores, whereas AVC = 0 was associated with an extremely low long-term risk of severe AS. The measurement of AVC provides clinically relevant information to assess an individual's long-term risk for severe AS.

Princeton IV consensus guidelines: PDE5 inhibitors and cardiac health.

BACKGROUND: In 1999, 1 year after the approval of the first oral phosphodiesterase type 5 (PDE5) inhibitor for the treatment of erectile dysfunction (ED), the first Princeton Consensus Conference was held to address the clinical management of men with ED who also had cardiovascular disease. These issues were readdressed in the second and third conferences. In the 13 years since the last Princeton Consensus Conference, the experience with PDE5 inhibitors is more robust, and recent new data have emerged regarding not only safety and drug-drug interactions, but also a potential cardioprotective effect of these drugs. AIM: In March 2023, an interdisciplinary group of scientists and practitioners met for the fourth Princeton Consensus Guidelines at the Huntington Medical Research Institutes in Pasadena, California, to readdress the cardiovascular workup of men presenting with ED as well as the approach to treatment of ED in men with known cardiovascular disease. METHOD: A series of lectures from experts in the field followed by Delphi-type discussions were developed to reach consensus. OUTCOMES: Consensus was reached regarding a number of issues related to erectile dysfunction and the interaction with cardiovascular health and phosphodiesterase-5 inhibitors. RESULTS: An algorithm based on recent recommendations of the American College of Cardiology and American Heart Association, including the use of computed tomography coronary artery calcium scoring, was integrated into the evaluation of men presenting with ED. Additionally, the issue of nitrate use was further considered in an algorithm regarding the treatment of ED patients with coronary artery disease. Other topics included the psychological effect of ED and the benefits of treating it; the mechanism of action of the PDE5 inhibitors; drug-drug interactions; optimizing use of a PDE5 inhibitors; rare adverse events; potential cardiovascular benefits observed in recent retrospective studies; adulteration of dietary supplements with PDE5 inhibitors; the pros and cons of over-the-counter PDE5 inhibitors; non-PDE5 inhibitor therapy for ED including restorative therapies such as stem cells, platelet-rich plasma, and shock therapy; other non-PDE5 inhibitor therapies, including injection therapy and penile prostheses; the issue of safety and effectiveness of PDE5 inhibitors in women; and recommendations for future studies in the field of sexual dysfunction and PDE5 inhibitor use were discussed. CLINICAL IMPLICATIONS: Algorithms and tables were developed to help guide the clinician in dealing with the interaction of ED and cardiovascular risk and disease. STRENGTHS AND LIMITATIONS: Strengths include the expertise of the participants and consensus recommendations. Limitations included that participants were from the United States only for this particular meeting. CONCLUSION: The issue of the intersection between cardiovascular health and sexual health remains an important topic with new studies suggesting the cardiovascular safety of PDE5 inhibitors.

Kidney function, bone-mineral metabolism markers, and calcification of coronary arteries, aorta, and cardiac valves in older adults.

BACKGROUND AND AIMS: The contribution of kidney dysfunction, especially at mild-to-moderate stages, and bone-mineral metabolism (BMM) markers to vascular calcification remains controversial or unclear. We comprehensively evaluated the association of kidney and BMM markers with coronary artery calcification (CAC) and extra-coronary calcification (ECC). METHODS: In 1931 ARIC participants (age 73-95 years) without coronary heart disease at visit 7 (2018-19), we investigated the associations of estimated glomerular filtration rate (eGFR) (with creatinine, cystatin C, and both) and five serum BMM markers (calcium, fibroblast growth factor 23, magnesium, parathyroid hormone, and phosphorus) with high CAC and ECC (sex-race specific ≥75th vs. <75th percentile Agatston score) or any vs. zero CAC and ECC using multivariable logistic regression. For eGFR and BMM markers, we took their weighted cumulative averages from visit 1 (1987-89) to visit 5 (2011-13). RESULTS: Lower eGFR, regardless of equations used, was not robustly associated with high CAC or ECC. Among BMM markers, only higher phosphorus levels, even within the normal range, showed robust associations with high CAC (only when modeled continuously) and ECC, independently of kidney function (e.g., odds ratio 1.94 [95%CI 1.38-2.73] for high aortic valve calcification, in the highest vs. lowest quartile). Results were generally consistent when analyzing any CAC or ECC, although cystatin C-based eGFR <60 mL/min/1.73 m2 became significantly associated with mitral valve calcification (odds ratio 1.69 [1.10-2.60]). CONCLUSIONS: Among kidney and BMM measures tested, only serum phosphorus demonstrated robust associations with both CAC and ECC, supporting a key role of phosphorus in the pathophysiology of vascular calcification.

Imaging subclinical coronary atherosclerosis to guide lipid management, are we there yet?

Atherosclerotic cardiovascular disease risk (ASCVD) is an ongoing epidemic, and lipid abnormalities are its primordial cause. Most individuals suffering a first ASCVD event are previously asymptomatic and often do not receive preventative therapies. The cornerstone of primary prevention has been the identification of individuals at risk through risk calculators based on clinical and laboratory traditional risk factors plus risk enhancers. However, it is well accepted that a clinical risk calculator misclassifies a significant proportion of individuals leading to the prescription of a lipid-lowering medication with very little yield or a missed opportunity for lipid-lowering agents with a potentially preventable event. The development of coronary artery calcium scoring (CAC) and CT coronary angiography (CCTA) provide complementary tools to directly visualize coronary plaque and other risk-modifying imaging components that can potentially provide individualized lipid management. Understanding patient selection for CAC or potentially CCTA and the risk implications of the different parameters provided, such as CAC score, coronary stenosis, plaque characteristics and burden, epicardial adipose tissue, and pericoronary adipose tissue, have grown more complex as technologies evolve. These parameters directly affect the shared decision with patients to start or withhold lipid-lowering therapies, to adjust statin intensity or LDL cholesterol goals. Emerging lipid lowering studies with non-invasive imaging as a guide to patient selection and treatment efficacy, plus the evolution of lipid lowering therapies from statins to a diverse armament of newer high-cost agents have pushed these two fields forward with a complex interaction. This review will discuss existing risk estimators, and non-invasive imaging techniques for subclinical coronary atherosclerosis, traditionally studied using CAC and more recently CCTA with qualitative and quantitative measurements. We will also explore the current data, gaps of knowledge and future directions on the use of these techniques in the risk-stratification and guidance of lipid management.

Association Between Omega-3 Fatty Acid Levels and Aortic Valve Calcium (from the Multi-Ethnic Study of Atherosclerosis).

Calcific aortic valve disease, a condition of chronic inflammation, is associated with increased cardiovascular events and all-cause mortality. Omega-3 fatty acids (O3FAs) reduce both acute and chronic inflammation, but their associations with aortic valve calcium (AVC) have not been studied. The Multi-Ethnic Study of Atherosclerosis is a prospective cohort study of 6,814 adults without clinical cardiovascular disease. Plasma fatty acid levels and cardiac computed tomography (CT) scans were performed at baseline, and CT scans were performed at subsequent clinical visits over a median 9-year period. We assessed whether plasma levels of O3FAs and their species correlate with the presence, severity, and progression of AVC measured by CT in Multi-Ethnic Study of Atherosclerosis. The mean age of the 6,510 included participants with baseline fatty acid levels, AVC, and covariate data was 62.1 ± 10.2 years, and 47.1% of the participants were male. Race distribution was 38.6% White, 27.2% Black, 22.1% Hispanic/Latino, and 12.1% Chinese. Among the 6,510 participants, 5,884 had a subsequent CT scan, and 3,304 had a third CT scan with AVC measurements. At baseline, 862 participants (13.2%) had prevalent AVC (Agatston score >0), and were more likely to be of older age, male, of the White race, have a lower education level, and have co-morbidities that are associated with a higher risk for AVC. Plasma tertiles of eicosapentaenoic acid, docosahexaenoic acid, and total O3FA were not associated with prevalent AVC at baseline, incident AVC, or change in AVC. In conclusion, plasma levels of O3FAs in subjects not routinely supplemented with O3FAs are not useful for predicting the presence or development of AVC. Whether high plasma O3FA levels, achievable by high-dose O3FA over-the-counter supplementation or pharmacotherapy, is associated with AVC requires further investigation.

Omega-3 fatty acids, subclinical atherosclerosis, and cardiovascular events: Implications for primary prevention.

BACKGROUND AND AIMS: High-dose eicosapentaenoic acid (EPA) therapy was beneficial in high-risk patients without clinical cardiovascular disease (CVD). Whether higher plasma levels of EPA and docosahexaenoic acid (DHA) have similar benefits in those without subclinical CVD is unclear. We aim to evaluate the interplay between plasma omega-3 fatty acids and coronary artery calcium (CAC) in relation to CVD events. METHODS: We examined 6568 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) with plasma EPA and DHA levels and CAC measured at baseline. The primary outcome was incident CVD events (myocardial infarction, angina, cardiac arrest, stroke, CVD death). Hazard ratios for the primary outcome were adjusted for potential confounder using Cox regression. RESULTS: Mean ± SD age was 62.1 ± 10.2 years and 52.9% were females. The median follow-up time was 15.6 years. Higher loge(EPA) (adjusted hazard ratio, aHR = 0.83; 95% CI, 0.74-0.94) and loge(DHA) (aHR = 0.79; 95% CI, 0.66-0.96) were independently associated with fewer CVD events. The difference in absolute CVD event rates between lowest vs. highest EPA tertile increased at higher CAC levels. The adjusted HR for highest vs. lowest EPA tertile within CAC = 0 was 1.02 (95% CI, 0.72-1.46), CAC = 1-99 was 0.71 (95% CI, 0.51-0.99), and CAC≥100 was 0.67 (95% CI, 0.52-0.84). A similar association was seen in tertiles of DHA by CAC category. CONCLUSIONS: In an ethnically diverse population free of clinical CVD, higher plasma omega-3 fatty acid levels were associated with fewer long-term CVD events. The absolute decrease in CVD events with higher omega-3 fatty acid levels was more apparent at higher CAC scores.

Association Between Omega-3 Fatty Acid Levels and Risk for Incident Major Bleeding Events and Atrial Fibrillation: MESA.

Background Randomized trials of pharmacologic strength omega-3 fatty acid (n3-FA)-based therapies suggest a dose-dependent cardiovascular benefit. Whether blood n3-FA levels also mediate safety signals observed in these trials, such as increased bleeding and atrial fibrillation (AF), remains uncertain. We hypothesized that higher baseline n3-FA levels would be associated with incident bleeding and AF events in MESA (Multi-Ethnic Study of Atherosclerosis), which included a population free of clinical cardiovascular disease at baseline. Methods and Results We examined the association between baseline plasma n3-FA levels (expressed as percent mass of total fatty acid) with incident bleeding and AF in MESA, an ongoing prospective cohort study. Bleeding events were identified from review of hospitalization International Classification of Diseases, Ninth Revision (ICD-9), and International Classification of Diseases, Tenth Revision (ICD-10), codes, and AF from participant report, discharge diagnoses, Medicare claims data, and study ECGs performed at MESA visit 5. Separate multivariable Cox proportional hazard modeling was used to estimate hazard ratios of the association of continuous n3-FA (log eicosapentaenoic acid [EPA], log docosahexaenoic acid [DHA], log [EPA+DHA]) and incident hospitalized bleeding events and AF. Among 6546 participants, the mean age was 62.1 years and 53% were women. For incident bleeding, consistent statistically significant associations with lower rates were seen with increasing levels of EPA and EPA+DHA in unadjusted and adjusted models including medications that modulate bleeding risk (aspirin, NSAIDS, corticosteroids, and proton pump inhibitors). For incident AF, a significant association with lower rates was seen with increasing levels of DHA, but not for EPA or EPA+DHA. Conclusions In MESA, higher plasma levels of n3-FA (EPA and EPA+DHA, but not DHA) were associated with significantly fewer hospitalized bleeding events, and higher DHA levels (but not EPA or EPA+DHA) with fewer incident AF events.

Association of types of dietary fats and all-cause and cause-specific mortality: A prospective cohort study and meta-analysis of prospective studies with 1,164,029 participants.

BACKGROUND: Associations between dietary fats and mortality are unclear. METHODS: We evaluated the relationship between quartiles of total fat, mono-unsaturated (MUFA), polyunsaturated (PUFA) and saturated fatty acid (SFA) consumption, and all-cause, coronary heart disease (CHD), stroke, and type 2 diabetes (T2D)-associated mortality in 24,144 participants from the National Health and Nutrition Examination Surveys (NHANES) 1999-2010. We added our results to a meta-analysis based on searches until November 2018. RESULTS: In fully adjusted Cox-proportional hazard models in our prospective study, there was an inverse association between total fat (HR: 0.90, 95% confidence interval 0.82, 0.99, Q4 vs Q1) and PUFA (0.81, 0.78-0.84) consumption and all-cause mortality, whereas SFA were associated with the increased mortality (1.08, 1.04-1.11). In the meta-analysis of 29 prospective cohorts (n = 1,164,029) we found a significant inverse association between total fat (0.89, 0.82-0.97), MUFA (0.94, 0.89-0.99) and PUFA (0.89, 0.84-0.94) consumption and all-cause mortality. No association was observed between total fat and CVD (0.93, 0.80-1.08) or CHD mortality (1.03 0.99-1.09). A significant association between SFA intake and CHD mortality (1.10, 1.01-1.21) was observed. Neither MUFA nor PUFA were associated with CVD or CHD mortality. Inverse associations were observed between MUFA (0.80, 0.67-0.96) and PUFA (0.84, 0.80-0.90) intakes and stroke mortality. CONCLUSIONS: We showed differential associations of total fat, MUFA and PUFA with all-cause mortality, but not CVD or CHD mortalities. SFA was associated with higher all-cause mortality in NHANES and with CHD mortality in our meta-analysis. The type of fat intake appears to be associated with important health outcomes.

Vitamin D supplementation and incident preeclampsia: A systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Maternal vitamin D deficiency has been associated with an increased risk for preeclampsia. Despite this, the current evidence regarding the efficacy of vitamin D supplementation in preventing preeclampsia is controversial. To assess the impact of vitamin D supplementation on the risk of preeclampsia, we performed a systematic review of the literature and a meta-analysis of the available randomized clinical trials (RCTs). METHODS: The primary outcome was preeclampsia. Subgroup analyses were carried out considering the timing of the supplementation, type of intervention and the study design. Meta-regression analysis, including the amount of vitamin D and maternal age, were planned to explore heterogeneity (PROSPERO database registration number: CRD42019119207). RESULTS: Data were pooled from 27 RCTs comprising 59 arms, which included overall 4777 participants, of whom 2487 were in the vitamin D-treated arm and 2290 in the control arm. Vitamin D administration in pregnancy was associated with a reduced risk of preeclampsia (odd ratio [OR] 0.37, 95% confidence interval [CI]: 0.26, 0.52; I2 = 0%). If the vitamin D supplementation was started up to 20 weeks' gestation, the odds was a little lower (OR 0.35, 95% CI: 0.24, 0.50, p < 0.001). The effect was largely independent of the supplementation cessation (until delivery or not), type of intervention (vitamin D alone or in association with calcium), and study design. Increasing dose of vitamin D was associated with reduced incidence of preeclampsia (slope of log OR: -1.1, 95% CI: -1.73, -0.46; p < 0.001). CONCLUSIONS: Results suggest that vitamin D supplementation may be useful in preventing preeclampsia. These data are especially useful for health-care providers who engage in the management of pregnant women at risk for preeclampsia. Our findings are a call for action to definitively address vitamin D supplementation as a possible intervention strategy in preventing preeclampsia in pregnancy.

Association of lowering apolipoprotein B with cardiovascular outcomes across various lipid-lowering therapies: Systematic review and meta-analysis of trials.

AIMS: The effect of therapeutic lowering of apolipoprotein B (apoB) on mortality and major adverse cardiovascular events is uncertain. It is also unclear whether these potential effects vary by different lipid-lowering strategies. METHODS: A total of 29 randomized controlled trials were selected using PubMed, Cochrane Library and EMBASE through 2018. We selected trials of therapies which ultimately clear apolipoprotein B particles by upregulating low-density lipoprotein receptor (LDL-R) expression (statins, ezetimibe, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, bile acid sequestrants) or therapies which reduce apolipoprotein B independent of LDL-R (cholesteryl ester transfer protein inhibitor, fibrates, niacin, omega-3 fatty acids) with sample size of ≥1000 patients and follow-up of ≥1 year. The meta-regression and meta-analyses were constructed using a random effects model. RESULTS: In 332,912 patients, meta-regression analyses showed relative risks of 0.95 for all-cause mortality (95% confidence interval 0.92-0.99) and 0.93 (0.88-0.98) for cardiovascular mortality for every 10 mg/dL decrease in apolipoprotein B by all interventions combined. Reduction in all-cause mortality was limited to statins (0.92 (0.86-0.98)). For MACE, the relative risk per 10 mg/dL reduction in apolipoprotein B was 0.93 (0.90-0.97) for all therapies combined, with both statin (0.88 (0.83-0.93)) and non-statin therapies (0.96 (0.94-0.99)). which clear apolipoprotein B by upregulating LDL-R showing significant reductions; whereas interventions which lower apolipoprotein B independent of LDL-R did not demonstrate this effect (1.02 (0.81-1.30)). CONCLUSION: While both statin and established non-statin therapies (PCSK9 inhibitor and ezetimibe) reduced cardiovascular risk per decrease in apolipoprotein B, interventions which reduce apolipoprotein B independently of LDL-R were not associated with cardiovascular benefit.

Effects of Nutritional Supplements and Dietary Interventions on Cardiovascular Outcomes: An Umbrella Review and Evidence Map.

Background: The role of nutritional supplements and dietary interventions in preventing mortality and cardiovascular disease (CVD) outcomes is unclear. Purpose: To examine evidence about the effects of nutritional supplements and dietary interventions on mortality and cardiovascular outcomes in adults. Data Sources: PubMed, CINAHL, and the Cochrane Library from inception until March 2019; ClinicalTrials.gov (10 March 2019); journal Web sites; and reference lists. Study Selection: English-language, randomized controlled trials (RCTs) and meta-analyses of RCTs that assessed the effects of nutritional supplements or dietary interventions on all-cause mortality or cardiovascular outcomes, such as death, myocardial infarction, stroke, and coronary heart disease. Data Extraction: Two independent investigators abstracted data, assessed the quality of evidence, and rated the certainty of evidence. Data Synthesis: Nine systematic reviews and 4 new RCTs were selected that encompassed a total of 277 trials, 24 interventions, and 992 129 participants. A total of 105 meta-analyses were generated. There was moderate-certainty evidence that reduced salt intake decreased the risk for all-cause mortality in normotensive participants (risk ratio [RR], 0.90 [95% CI, 0.85 to 0.95]) and cardiovascular mortality in hypertensive participants (RR, 0.67 [CI, 0.46 to 0.99]). Low-certainty evidence showed that omega-3 long-chain polyunsaturated fatty acid (LC-PUFA) was associated with reduced risk for myocardial infarction (RR, 0.92 [CI, 0.85 to 0.99]) and coronary heart disease (RR, 0.93 [CI, 0.89 to 0.98]). Folic acid was associated with lower risk for stroke (RR, 0.80 [CI, 0.67 to 0.96]; low certainty), whereas calcium plus vitamin D increased the risk for stroke (RR, 1.17 [CI, 1.05 to 1.30]; moderate certainty). Other nutritional supplements, such as vitamin B6, vitamin A, multivitamins, antioxidants, and iron and dietary interventions, such as reduced fat intake, had no significant effect on mortality or cardiovascular disease outcomes (very low- to moderate-certainty evidence). Limitations: Suboptimal quality and certainty of evidence. Conclusion: Reduced salt intake, omega-3 LC-PUFA use, and folate supplementation could reduce risk for some cardiovascular outcomes in adults. Combined calcium plus vitamin D might increase risk for stroke. Primary Funding Source: None.

Association Between Self-rated Health, Coronary Artery Calcium Scores, and Atherosclerotic Cardiovascular Disease Risk: The Multi-Ethnic Study of Atherosclerosis (MESA).

Importance: The interplay of self-rated health (SRH), coronary artery calcium (CAC) scores, and cardiovascular risk is poorly described. Objectives: To assess the degree of correlation between SRH and CAC, to determine whether these measures are complementary for risk prediction, and to assess the incremental value of the addition of SRH to established risk tools. Design, Setting, and Participants: The Multi-Ethnic Study of Atherosclerosis (MESA) is a large population-based prospective cohort study of adults aged 45 to 84 years who were recruited from 6 US communities. A total of 6764 participants without baseline cardiovascular disease (CVD) were included in the analysis. Data were collected from July 2000 through August 2002. Follow-up was completed by December 2013, and data were analyzed from October 2018 to December 2018. Exposures: The EVGGFP (excellent, very good, good, fair, and poor) self-assessment of overall health (assessed before the baseline study examination) and CAC score. The EVGGFP rating was categorized as poor/fair, good, very good, or excellent. Main Outcomes and Measures: Hard coronary heart disease (CHD) events, hard CVD events, and all-cause mortality during a median follow-up of 13.2 years (interquartile range, 12.7-13.7 years). Results: Among the study population of 6764 participants, the mean (SD) age was 62.1 (10.2) years, and 52.9% were women. The EVGGFP rating was strongly associated with age, sex, race/ethnicity, educational and income levels, healthy diet and physical activity, and cardiovascular risk factors. Despite encapsulating many risk variables, no correlation (r = -0.007; P = .57) or association between EVGGFP and the presence (χ2 = 0.84; P = .84) or severity (χ2 = 4.64; P = .86) of CAC was found. During follow-up, 1161 deaths, 637 hard CVD events, and 405 hard CHD events were recorded. In models adjusted for age, sex, race/ethnicity, and CAC, participants who reported excellent health had a 45% lower risk of CVD (hazard ratio [HR], 0.55; 95% CI, 0.39-0.77) and a 42% lower risk of CHD (HR, 0.58; 95% CI, 0.37-0.90) compared with those who reported poor/fair health. Participants in the excellent SRH category who had any CAC had markedly elevated risk of hard CHD (HR, 6.19; 95% CI, 2.1-18.3) and CVD (HR, 6.50; 95% CI, 2.7-15.6) events compared with those with a CAC score of 0. The addition of the EVGGFP rating to CAC improved the area under the curve (C statistic) for CHD events (0.725 vs 0.734; P = .007), CVD events (0.693 vs 0.706; P < .001), and all-cause mortality (0.685 vs 0.707; P < .001). However, the addition of the EVGGFP rating to the combination of CAC and atherosclerotic CVD risk score did not significantly improve C statistics for CHD events (0.751 vs 0.753; P = .39), CVD events (0.739 vs 0.741; P = .18), or all-cause mortality (0.779 vs 0.781; P = .13). Conclusions and Relevance: Although SRH and CAC integrate many risk variables, this study suggests that they are poorly correlated and have complementary predictive utility. A perception of excellent health does not obviate the need for definitive assessment of CVD risk, whereas fair/poor perceived health may serve as a risk enhancer, arguing for advanced risk assessment in selected clinical scenarios.

Age- and gender-adjusted percentiles for number of calcified plaques in coronary artery calcium scanning.

BACKGROUND: Age- and gender-adjusted percentiles of coronary artery calcium (CAC) score are commonly reported to compare a patient's coronary atherosclerosis burden to that of others of the same age and gender. The number of calcified plaques (numCP) detected on CAC scanning, a measure of plaque diffusivity, is associated with increased cardiovascular risk and, in the intermediate CAC range, adds to the CAC score in predicting mortality. This study aims to develop adjusted percentiles for numCP to provide a better context for understanding CAC scan findings. METHODS AND RESULTS: Using nonparametric modeling techniques, the distribution of numCP was analyzed in 70,320 consecutive, asymptomatic patients without prior clinically-diagnosed cardiovascular disease who were part of the Coronary Artery Calcium Consortium and supplemented by additional patients referred for clinical CAC scanning in a single center between 1998 and 2016. Nomograms for age-adjusted numCP percentiles for each gender were generated using quantile regression. The prevalence and average number of calcified coronary plaque were found to be higher in men than women. Distribution of numCP in women was found to closely mirror that of men approximately a decade younger. NumCP increased consistently across age groups in both men and women for each quantile category. CONCLUSIONS: A nomogram for age and gender-adjusted percentiles for the numCP on CAC scans has been developed in a large population of asymptomatic patients studied across multiple centers. This numCP nomogram may provide an additional tool for refining physician recommendations regarding treatment and expressing to patients how their CAC findings relate to others of similar age and gender. The numCP percentiles may also provide a meaningful way to evaluate and report the rate of progression of CAC on serial studies.

Synergistic Opportunities in the Interplay Between Cancer Screening and Cardiovascular Disease Risk Assessment: Together We Are Stronger.

Cardiovascular disease (CVD) and cancer continue to be the 2 leading causes of death in developed countries despite significant improvements in the prevention, screening, and treatment of both diseases. They remain significant public health problems, growing in importance globally. Despite this threat, the fields of cardiology and oncology have been relatively disconnected. With many shared modifiable risk factors, cancer and CVD often coexist in the same individuals; those diagnosed with lung cancer, breast cancer, and colon cancer are at higher risk of CVD, and those with CVD are at higher risk of developing many types of common cancers. Screening paradigms have been established in parallel, but there are opportunities for combined risk assessments for cancer and CVD risk. Joining forces for combined cardiovascular and hemato-oncological preventive and research efforts will likely have synergistic, worldwide public health benefits.

Association of Multivitamin and Mineral Supplementation and Risk of Cardiovascular Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Multiple studies have attempted to identify the association between multivitamin/mineral (MVM) supplementation and cardiovascular disease (CVD) outcomes, but the benefits remain controversial. We performed a systematic review and meta-analysis of the associations between MVM supplementation and various CVD outcomes, including coronary heart disease (CHD) and stroke. METHODS AND RESULTS: We conducted a comprehensive search of Medline, Embase, and the Cochrane Library for studies published between January 1970 and August 2016. We included clinical trials and prospective cohort studies in the general population evaluating associations between MVM supplementation and CVD outcomes. Data extraction and quality assessment were independently conducted by 2 authors, and a third author resolved discrepancies. Eighteen studies with 2 019 862 participants and 18 363 326 person-years of follow-up were included in the analysis. Five studies specified the dose/type of MVM supplement and the rest did not. Overall, there was no association between MVM supplementation and CVD mortality (relative risk [RR], 1.00; 95% confidence interval [CI], 0.97-1.04), CHD mortality (RR, 1.02; 95% CI, 0.92-1.13), stroke mortality (RR, 0.95; 95% CI, 0.82-1.09), or stroke incidence (RR, 0.98; 95% CI, 0.91-1.05). There was no association between MVM supplements and CVD or CHD mortality in prespecified subgroups categorized by mean follow-up period, mean age, period of MVM use, sex, type of population, exclusion of patients with history of CHD, and adjustment for diet, adjustment for smoking, adjustment for physical activity, and study site. In contrast, MVM use did seem to be associated with a lower risk of CHD incidence (RR, 0.88; 95% CI, 0.79-0.97). However, this association did not remain significant in the pooled subgroup analysis of randomized controlled trials (RR, 0.97; 95% CI, 0.80-1.19). CONCLUSIONS: Our meta-analysis of clinical trials and prospective cohort studies demonstrates that MVM supplementation does not improve cardiovascular outcomes in the general population.

Coronary Artery Calcium Scoring in Current Clinical Practice: How to Define Its Value?

OPINION STATEMENT: Detecting subclinical atherosclerosis with coronary artery calcium (CAC) is promising for identifying individuals at risk for cardiovascular events and appears to be a robust tool for guiding initiation of appropriate and timely primary prevention strategies. However, how do we best determine its clinical value? It is clear that traditional risk prediction models based primarily on age, gender, and risk factors are insufficient for ideal personalization of risk estimation. It is now well established from epidemiologic studies that CAC adds to traditional risk scores for a more accurate risk prediction. However, such traditional epidemiology studies have limitations in establishing "clinical value," and they must be supplemented by additional data before being translated into strong recommendations in clinical practice guidelines. Fortunately, over the last few years, the research around CAC has matured to include data supporting enhanced clinician-patient risk discussions, shared decision-making, flexible risk factor treatment goals, specific clinical decision algorithms, as well as favorable cost-effectiveness analyses. We had moved from a time when we asked "if CAC adds to the risk score" to a time when we are asking "does CAC facilitate a shared decision-making model matching risk, treatment, and patient preferences?" A new risk calculator incorporating CAC into global risk scoring, and 2017 guidelines on the use of CAC published by the Society of Cardiovascular Computed Tomography (SCCT), reflect this new approach. In this article, we review the recent transition to this more clinically relevant CAC research that may support a stronger recommendation for its use in future prevention guidelines.

Does vitamin D supplementation alter plasma adipokines concentrations? A systematic review and meta-analysis of randomized controlled trials.

We aimed to elucidate the role of vitamin D supplementation on adipokines through a systematic review and a meta-analysis of randomized placebo-controlled trials (RCTs). The search included PUBMED, Scopus, Web of Science and Google Scholar through July 1st, 2015. Finally we identified 9 RCTs and 484 participants. Meta-analysis of data from 7 studies did not find a significant change in plasma adiponectin concentrations following vitamin D supplementation (mean difference [MD]: 4.45%, 95%CI: -3.04, 11.93, p=0.244; Q=2.18, I(2)=0%). In meta-regression, changes in plasma adiponectin concentrations following vitamin D supplementation were found to be independent of treatment duration (slope: 0.25; 95%CI: -0.69, 1.19; p=0.603) and changes in serum 25-hydroxy vitamin D [25(OH)D] levels (slope: -0.02; 95%CI: -0.15, 0.12; p=0.780). Meta-analysis of data from 6 studies did not find a significant change in plasma leptin concentrations following vitamin D supplementation (MD: -4.51%, 95%CI: -25.13, 16.11, p=0.668; Q=6.41, I(2)=21.97%). Sensitivity analysis showed that this effect size is sensitive to one of the studies; removing it resulted in a significant reduction in plasma leptin levels (MD: -12.81%, 95%CI: -24.33, -1.30, p=0.029). In meta-regression, changes in plasma leptin concentrations following vitamin D supplementation were found to be independent of treatment duration (slope: -1.93; 95%CI: -4.08, 0.23; p=0.080). However, changes in serum 25(OH)D were found to be significantly associated with changes in plasma leptin levels following vitamin D supplementation (slope: 1.05; 95%CI: 0.08, 2.02; p=0.033). In conclusion, current data did not indicate a significant effect of vitamin D supplementation on adiponectin and leptin levels.