Familial hypercholesterolemia/autosomal dominant hypercholesterolemia: Molecular defects, the LDL-C continuum, and gradients of phenotypic severity.

BACKGROUND: Familial hypercholesterolemia (FH) is a common inherited disorder in which the severity of atherosclerosis is generally proportional to the extent and duration of elevated plasma low-density lipoprotein cholesterol (LDL-C) levels. Homozygous FH (HoFH) is generally considered the most severe condition and results in very high LDL-C levels that respond only partially to statin therapy. The diagnosis of HoFH is complicated by its presentation as a phenotypic spectrum involving multiple genes. OBJECTIVE: The objective here is to review the genetics, continuum of LDL-C concentrations, and phenotypic severity of FH. METHODS: Multiple PubMed searches were conducted as described in the main text of this article. RESULTS: Traditionally, FH has been considered an autosomal co-dominant disorder whereby both heterozygotes (HeFH) and homozygotes are affected. Recently, additional genes and loci for monogenic FH have been characterized that allow for the identification of double mutations in the known genes and loci and the description of novel forms of double heterozygous FH. Phenotypic expression and clinical severity of untreated HeFH, double HeFH, compound HeFH, and HoFH vary with some overlap both between and within the genotypes. In addition, there is overlap in LDL-C levels of treated HeFH and treated HoFH. CONCLUSIONS: These discoveries raise the possibility that new combinations of molecular defects could modulate the severity of hypercholesterolemia. These defects are unlikely to represent true homozygosity. However, they are likely to result in a phenotype consistent with HoFH or severe HeFH, which will be important as new therapies become available with indications specifically for HoFH.

Young Hispanic Women Experience Higher In-Hospital Mortality Following an Acute Myocardial Infarction.

BACKGROUND: Although mortality rates for acute myocardial infarction (AMI) have declined for men and women, prior studies have reported a sex gap in mortality such that younger women were most likely to die after an AMI. METHODS AND RESULTS: We sought to explore the impact of race and ethnicity on the sex gap in AMI patterns of care and mortality for younger women in a contemporary patient cohort. We constructed multivariable hierarchical logistic regression models to examine trends in AMI hospitalizations, procedures, and in-hospital mortality by sex, age (<65 and ≥65 years), and race/ethnicity (white, black, and Hispanic). Analyses were derived from 194 071 patients who were hospitalized for an AMI with available race and ethnicity data from the 2009-2010 National Inpatient Sample. Hospitalization rates, procedures (coronary angiography, percutaneous coronary interventions, and cardiac bypass surgery), and inpatient mortality were analyzed across age, sex, and race/ethnic groups. There was significant variation in hospitalization rates by age and race/ethnicity. All racial/ethnic groups were less likely to undergo invasive procedures compared with white men (P<0.001). After adjustment for comorbidities, younger Hispanic women experienced higher in-hospital mortality compared with younger white men, with an odds ratio of 1.5 (95% CI 1.2 to 1.9), adjusted for age and comorbidities. CONCLUSION: We found significant racial and sex disparities in AMI hospitalizations, care patterns, and mortality, with higher in-hospital mortality experienced by younger Hispanic women. Future studies are necessary to explore determinants of these significant racial and sex disparities in outcomes for AMI.

National trends in patient safety for four common conditions, 2005-2011.

BACKGROUND: Changes in adverse-event rates among Medicare patients with common medical conditions and conditions requiring surgery remain largely unknown. METHODS: We used Medicare Patient Safety Monitoring System data abstracted from medical records on 21 adverse events in patients hospitalized in the United States between 2005 and 2011 for acute myocardial infarction, congestive heart failure, pneumonia, or conditions requiring surgery. We estimated trends in the rate of occurrence of adverse events for which patients were at risk, the proportion of patients with one or more adverse events, and the number of adverse events per 1000 hospitalizations. RESULTS: The study included 61,523 patients hospitalized for acute myocardial infarction (19%), congestive heart failure (25%), pneumonia (30%), and conditions requiring surgery (27%). From 2005 through 2011, among patients with acute myocardial infarction, the rate of occurrence of adverse events declined from 5.0% to 3.7% (difference, 1.3 percentage points; 95% confidence interval [CI], 0.7 to 1.9), the proportion of patients with one or more adverse events declined from 26.0% to 19.4% (difference, 6.6 percentage points; 95% CI, 3.3 to 10.2), and the number of adverse events per 1000 hospitalizations declined from 401.9 to 262.2 (difference, 139.7; 95% CI, 90.6 to 189.0). Among patients with congestive heart failure, the rate of occurrence of adverse events declined from 3.7% to 2.7% (difference, 1.0 percentage points; 95% CI, 0.5 to 1.4), the proportion of patients with one or more adverse events declined from 17.5% to 14.2% (difference, 3.3 percentage points; 95% CI, 1.0 to 5.5), and the number of adverse events per 1000 hospitalizations declined from 235.2 to 166.9 (difference, 68.3; 95% CI, 39.9 to 96.7). Patients with pneumonia and those with conditions requiring surgery had no significant declines in adverse-event rates. CONCLUSIONS: From 2005 through 2011, adverse-event rates declined substantially among patients hospitalized for acute myocardial infarction or congestive heart failure but not among those hospitalized for pneumonia or conditions requiring surgery. (Funded by the Agency for Healthcare Research and Quality and others.).

Familial hypercholesterolemia: an under-recognized but significant concern in cardiology practice.

Familial hypercholesterolemia (FH) is a common disorder in which genetic mutations in at least 1 of several genes lead to significantly increased levels of lipoproteins, in particular, low-density lipoprotein cholesterol. Most commonly, mutations in the low-density lipoprotein receptor gene result in high plasma levels of apolipoprotein B-containing lipoproteins (eg, low-density lipoprotein and lipoprotein(a)). High plasma levels of lipoproteins increase the risk of cardiovascular events by as much as 20-fold if left untreated. A 2011 survey of cardiologists performed by the American College of Cardiology (ACC) suggests that there is a need for greater awareness of FH among cardiologists with regard to its prevalence and heritability, and of the risk of cardiovascular (CV) disease associated with the disorder, such as premature coronary heart disease. Given that many patients with FH may first present to CV specialists at the time of a major coronary event, it is critical that cardiologists have strategies to manage this high-risk subset of patients. This brief review responds to areas of need identified in the ACC survey and is intended to provide current information about FH and increase awareness about this disorder among cardiologists.

Relation between time of symptom onset of ST-segment elevation myocardial infarction and patient baseline characteristics: from the National Cardiovascular Data Registry.

BACKGROUND: The presence of a morning excess of ST-segment elevation myocardial infarction (STEMI) has been observed. The relation between patient characteristics and timing of STEMI may provide insight into the biological processes responsible for this phenomenon. HYPOTHESIS: Patient baseline characteristics will vary with timing of STEMI. METHODS: We performed an analysis using a large national registry of unselected patients with STEMI (N=45,218). Patients were categorized by time of symptom onset: early (6 am-2 pm), late day (2 pm-10 pm), and overnight (10 pm-6 am) then evaluated for variations in characteristics. RESULTS: A circadian variation in the timing of symptom onset of STEMI was observed (early 41%, late day 32%, and overnight 26%, P<0.001). Circadian variations in factors known to alter timing of events were seen, including lower rates of home ß-blocker use, smoking, and diabetes, with early onset of STEMI symptoms. In addition, patients in the 6 am to 2 pm subgroup were more likely older, white race, and male, with higher rates of home aspirin use and lower rates of obesity. Higher rates of coexisting cardiovascular disease, including prior heart failure, 3-vessel coronary artery disease, and depressed left ventricular ejection fraction, were observed in the overnight group. More robust antiplatelet therapy with home clopidogrel use was not associated with a change in the timing of events. CONCLUSIONS: A morning excess of STEMI continues to exist and represents a potential target for preventative strategies. Patient baseline characteristics vary with the onset of STEMI and may reflect a physiologic relationship between these factors and the timing of events.

Characteristics of women lost to follow-up in cardiovascular community health interventions: findings from the Sister to Sister campaign.

Community-based interventions (CBI) have been targeted as a potential means of tackling cardiovascular disease in women. However, there have been mixed results in terms of their impact on health, with at least some of this being attributed to high attrition rates. This study explores factors that may be contributing to the low retention of women in cardiovascular CBIs. In 2009, Sister to Sister, a national organization that sponsors community health fairs, provided free cardiovascular health screenings for a total of 9,443 women nationwide. All participants were invited to enroll in a 1 year, survey-based observational study to assess the effectiveness of these community health screenings. Of these 9,443 women, 5.9 % actively participated in the follow-up study. Participants were more likely to have health insurance (75.5 vs. 65.3 %, p < 0.001), have an annual income above 75,000 dollars (26.7 vs. 19.7 %, p < 0.001), and identify themselves as white (50.0 vs. 31.5 %, p < 0.001). They were also more likely to have hypertension (32.1 vs. 27.4 %, p = 0.018) and metabolic syndrome (35.7 vs. 20.4 %, p < 0.001). Our results suggest that white, affluent women with health insurance and cardiovascular risk factors are more likely to engage in CBIs that require longitudinal assessment. This study gives insight into the demographics, socioeconomic status, and cardiovascular comorbidities of women who participate in cardiovascular CBIs. The results may prove to be useful in understanding the biopsychosocial barriers to participation in CBIs in order to develop more effective interventions in the future.

High prevalence of metabolic syndrome in young Hispanic women: findings from the national Sister to Sister campaign.

BACKGROUND: Hispanics are the fastest growing segment of the U.S. population and have a higher prevalence of cardiometabolic risk factors as compared with non-Hispanic whites. Further data suggests that Hispanics have undiagnosed complications of metabolic syndrome, namely diabetes mellitus, at an earlier age. We sought to better understand the epidemiology of metabolic syndrome in Hispanic women using data from a large, community-based health screening program. METHODS: Using data from the Sister to Sister: The Women's Heart Health Foundation community health fairs from 2008 to 2009 held in 17 U.S. cities, we sought to characterize how cardiometabolic risk profiles vary across age for women by race and ethnicity. Metabolic syndrome was defined using the updated National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) guidelines, which included three or more of the following: Waist circumference ≥35 inches, triglycerides ≥150 mg/dL, high-density lipoprotein (HDL) <50 mg/dL, systolic blood pressure ≥130 mmHg or diastolic blood pressure ≥85 mmHg, or a fasting glucose ≥100 mg/dL. RESULTS: A total of 6843 community women were included in the analyses. Metabolic syndrome had a prevalence of 35%. The risk-adjusted odds ratio for metabolic syndrome in Hispanic women versus white women was 1.7 (95% confidence interval, 1.4, 2.0). Dyslipidemia was the strongest predictor of metabolic syndrome among Hispanic women. This disparity appeared most pronounced for younger women. Additional predictors of metabolic syndrome included black race, increasing age, and smoking. CONCLUSIONS: In a large, nationally representative sample of women, we found that metabolic syndrome was highly prevalent among young Hispanic women. Efforts specifically targeted to identifying these high-risk women are necessary to prevent the cardiovascular morbidity and mortality associated with metabolic syndrome.

The DHHS Office on Women's Health Initiative to Improve Women's Heart Health: focus on knowledge and awareness among women with cardiometabolic risk factors.

UNLABELLED: Abstract Background: The diversity of the U.S. population and disparities in the burden of cardiovascular disease (CVD) require that public health education strategies must target women and racial/ethnic minority groups to reduce their CVD risk factors, particularly in high-risk communities, such as women with the metabolic syndrome (MS). METHODS: The data reported here were based on a cross-sectional face-to-face survey of women recruited from four participating sites as part of the national intervention program, Improving, Enhancing and Evaluating Outcomes of Comprehensive Heart Care in High-Risk Women. Measures included baseline characteristics, sociodemographics, CVD related-knowledge and awareness, and Framingham risk score (FRS). RESULTS: There were 443 of 698 women (63.5%) with one or more risk factors for the MS: non-Hispanic white (NHW), 51.5%; non-Hispanic black (NHB), 21.0%; Hispanic, 22.6%. Greater frequencies of MS occurred among Hispanic women (p<0.0001), those with less than a high school education (70.0%) (p<0.0001), Medicaid recipients (57.8%) (p<0.0001), and urbanites (43.3%) (p<0.001). Fewer participants with MS (62.6%) knew the leading cause of death compared to those without MS (72.1%) (p<0.0001). MS was associated with a lack of knowledge of the composite of knowing the symptoms of a heart attack plus the need to call 911 (odds ratio [OR] 0.41, 95% confidence interval [CI] 0.17-0.97, p=0.04). CONCLUSIONS: Current strategies to decrease CVD risk are built on educating the public about traditional factors, including hypertension, smoking, and elevated low-density lipoprotein cholesterol (LDL-C). An opportunity to broaden the scope for risk reduction among women with cardiometabolic risk derives from the observation that women with the MS have lower knowledge about CVD as the leading cause of death, the symptoms of a heart attack, and the ideal option for managing a CVD emergency.

Geographic variance of cardiovascular risk factors among community women: the national Sister to Sister campaign.

BACKGROUND: There are substantial variations in cardiovascular disease (CVD) risk and outcomes among women. We sought to determine geographic variation in risk factor prevalence in a contemporary sample of U.S. women. METHODS: Using 2008-2009 Sister to Sister (STS) free heart screening data from 17 U.S. cities, we compared rates of obesity (body mass index [BMI] ≥30 kg/m(2)), hypertension (HTN ≥140/90 mm Hg), low high-density lipoprotein cholesterol (HDL-C <40 mg/dL), and hyperglycemia (≥126 mg/dL) with national rates. RESULTS: In 18,892 women (mean age 49.8 ± 14.3 years, 37% black, 32% white, 14% Hispanic), compared to overall STS rates, significantly higher rates were observed for obesity in Baltimore (42.4%), Atlanta (40.0%), Dallas (37.9%), and Jacksonville (36.0%); for HTN in Atlanta (43.9%), Baltimore (42.5%), and New York (39.1%); for hyperglycemia in Jacksonville (20.3%), Philadelphia (18.1%), and Tampa (17.8%); and for HDL-C <40 mg/dL in Phoenix (37.4%), Dallas (26.5%), and Jacksonville (18.1%). Compared to national American Heart Association (AHA) 2010 update rates, most STS cities had higher rates of hyperglycemia and low HDL-C. CONCLUSIONS: In a large, community-based sample of women nationwide, this comprehensive analysis shows remarkable geographic variation in risk factors, which provides opportunities to improve and reduce a woman's CVD risk. Further investigation is required to understand the reasons behind such variation, which will provide insight toward tailoring preventive interventions to narrow gaps in CVD risk reduction in women.

Recognizing and improving health care disparities in the prevention of cardiovascular disease in women.

Innate differences in gender physiology result in unique exposures, risk, and protection that are specific to women. Recognition and appreciation of these differences results in better treatment adaptations for women and better outcomes. Disparities between genders in the treatment of major cardiovascular risk factors still exist and are mostly secondary to underestimating or misunderstanding a woman's risk. Preventive therapies are less often recommended to women. Women are more likely to be diagnosed and treated for hypertension, but are less likely to reach treatment goals. High-risk women-including diabetic women-are less likely to be on lipid-lowering agents and reach a low-density lipoprotein level less than 100 mg/dL. Diabetic women are less likely to achieve a hemoglobin A(1c) level less than 7%. Through understanding these disparities, health care providers will be better able to screen female patients and institute evidence-based therapies for the prevention of cardiovascular disease.

Core components of cardiac rehabilitation/secondary prevention programs: 2007 update: a scientific statement from the American Heart Association Exercise, Cardiac Rehabilitation, and Prevention Committee, the Council on Clinical Cardiology; the Councils on Cardiovascular Nursing, Epidemiology and Prevention, and Nutrition, Physical Activity, and Metabolism; and the American Association of Cardiovascular and Pulmonary Rehabilitation.

The American Heart Association and the American Association of Cardiovascular and Pulmonary Rehabilitation recognize that all cardiac rehabilitation/secondary prevention programs should contain specific core components that aim to optimize cardiovascular risk reduction, foster healthy behaviors and compliance to these behaviors, reduce disability, and promote an active lifestyle for patients with cardiovascular disease. This update to the previous statement presents current information on the evaluation, interventions, and expected outcomes in each of the core components of cardiac rehabilitation/secondary prevention programs, in agreement with the 2006 update of the American Heart Association/American College of Cardiology Secondary Prevention Guidelines, including baseline patient assessment, nutritional counseling, risk factor management (lipids, blood pressure, weight, diabetes mellitus, and smoking), psychosocial interventions, and physical activity counseling and exercise training.

Trends in acute myocardial infarction in 4 US states between 1992 and 2001: clinical characteristics, quality of care, and outcomes.

BACKGROUND: Because of the health impact of acute myocardial infarction (AMI), substantial resources have been dedicated to improving AMI care and outcomes. Long-term trends in the clinical characteristics, quality of care, and outcomes for AMI over time from the health system perspective in geographically diverse populations are not well known. METHODS AND RESULTS: The present study included 20,550 Medicare patients aged > or = 65 years hospitalized in 4 US states (Alabama, Connecticut, Iowa, Wisconsin) with the confirmed primary discharge diagnosis of AMI in 4 periods: 1992-1993 (n=10,292), 1995 (n=5566), 1998-1999 (n=2413), and 2000-2001 (n=2279). With the use of standard quality indicator definitions, treatment of ideal candidates with aspirin and beta-blockers within 24 hours after presentation, beta-blockers, and angiotensin-converting enzyme inhibitors at discharge was assessed. Multivariable models were constructed to calculate adjusted 1-year mortality. The hospitalized Medicare population with AMI changed substantially during 1992-2001, with increasing age, more comorbidity, and fewer meeting ideal treatment criteria. Although treatment rates increased significantly for all medications, aspirin, beta-blockers, and angiotensin-converting enzyme inhibitors were not provided at discharge to 12.6%, 19.7%, and 25.2% of ideal candidates, respectively, in 2000-2001. Crude 1-year mortality increased (27.6%, 28.3%, 30.6%, and 31.0%; P=0.003 for trend, but adjusted mortality declined (compared with 1992-1993, relative risk in 1995=0.94 [95% CI, 0.88 to 1.01]; relative risk in 1998-1999=0.91 [95% CI, 0.85 to 0.98]; relative risk in 2000-2001=0.87 [95% CI, 0.81 to 0.94]). CONCLUSIONS: The quality of care and adjusted 1-year mortality improved significantly for Medicare beneficiaries with AMI during 1992-2001. Nevertheless, fewer were ideal for guideline-based therapy, and absolute mortality remains high, suggesting the need for treatment strategies applicable to a broader range of older patients.

Anemia and outcomes in patients with heart failure: a study from the National Heart Care Project.

BACKGROUND: Recent reports have suggested that anemia is associated with adverse outcomes in patients with heart failure (HF), but were unable to adjust for a broad range of comorbid conditions. As a result, whether anemia is a truly independent predictor of risk or a marker of comorbid illness in these patients is unknown. METHODS: We analyzed medical records from the Centers for Medicare & Medicaid Services' National Heart Care Project, a national sample of 50,405 patients 65 years and older admitted to acute care hospitals with a principal discharge diagnosis of HF between April 1, 1998, and March 31, 1999, or between July 1, 2000, and June 30, 2001. Multivariable logistic regression analyses were conducted to test whether hematocrit level was an independent predictor of all-cause mortality and HF-related readmission at 1 year. RESULTS: In unadjusted analysis, lower hematocrit levels were associated with increased 1-year mortality and readmission for HF. Compared with patients with a hematocrit greater than 40% to 44%, those with a hematocrit of 24% or less had a 51% higher risk of death (relative risk [RR], 1.51; 95% confidence interval [CI], 1.35-1.68; P<.001) and a 17% higher risk of HF-related readmission (RR, 1.17; 95% CI, 1.01-1.34; P = .04). However, after adjustment for multiple comorbidities and other clinical factors, the association between lower hematocrit levels and increased 1-year mortality was markedly attenuated, even in those patients with the most severe anemia (hematocrit, < or = 24% vs > 40%-44%: RR, 1.02; 95% CI, 0.86-1.19; P = .85). The association between lower hematocrit values and HF-related readmission persisted after multivariable adjustment (hematocrit, < or = 24% vs > 40%-44%: RR, 1.21; 95% CI, 1.04-1.38; P = .01). CONCLUSIONS: Although anemia is an independent predictor of hospital readmission, its relationship with increased mortality in HF patients is largely explained by the severity of comorbid illness. These findings suggest that anemia may be predominantly a marker rather than a mediator of increased mortality risk in older patients with HF.

Lipid management in patients with unstable angina pectoris and non-ST-segment elevation acute myocardial infarction (from CRUSADE).

We sought to characterize current patterns of care for lipid testing and management in a sample of patients in the Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the American College of Cardiology/American Heart Association Guidelines Quality Improvement Initiative and to determine the most important predictors of lipid testing and management at discharge. We evaluated data from >40,000 patients who had been hospitalized in United States hospitals from March 2000 to March 2003 and had a principal discharge diagnosis of unstable angina pectoris or non-ST-segment elevation acute myocardial infarction as part of the initiative.

The prognostic value of vasodilator myocardial perfusion imaging in octogenarians.

The ability of single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) to stratify risk in octogenarians is poorly defined. The authors identified 439 octogenarians who underwent vasodilator SPECT MPI between 1994 and 2000. Over a mean 2.5 years of follow-up, moderate and large stress defects were associated with increased crude mortality (normal: 24.5%, small defect: 21.9%, moderate or large stress defect: 41.4%, p for trend < 0.001). The degree of defect reversibility was also strongly associated with increased mortality (normal: 24.5%, no reversibility: 22.0%, small reversible defect: 36.5%, moderate or large reversible defect: 50.0%, p for trend < 0.001). In multivariable analysis, stress defects were the strongest predictor of mortality (hazard ratio, 2.39; 95% confidence interval, 1.56-3.65). The mortality of octogenarians with moderate or large perfusion defects is nearly double that of patients with normal or mildly abnormal MPI. Appropriately selected octogenarians with abnormal vasodilator SPECT imaging may benefit from more aggressive management of their cardiac disease.