Polycystic ovary syndrome: A review of diagnosis and management, with special focus on atherosclerotic cardiovascular disease prevention.

Polycystic ovary syndrome (PCOS) is a common endocrinopathy worldwide with a heterogeneous clinical presentation including reproductive, metabolic, and endocrine elements. However, the assessment and management of PCOS remains inconsistent, with many women undiagnosed and untreated. We now also understand that the management of PCOS should extend throughout a woman's lifespan as many elements of the syndrome persist after menopause. Management has traditionally focused on the treatment of hyperandrogenism and oligomenorrhea. Women with PCOS often have dyslipidemia, hypertension, obesity, and metabolic syndrome, which may be worsened by the hormonal abnormalities, and are therefore at higher risk for cardiovascular disease morbidity and mortality, a risk that increases after menopause. While treatment with hormonal therapy, in particular combined oral contraceptives, may improve cardiovascular risk factors, management plans should incorporate specific diagnosis and management of these factors, if present, because of the strong contribution to the risk for atherosclerotic cardiovascular disease (ASCVD). Given the complexities of the syndrome, optimal management often requires a multi-disciplinary approach including the lipid and cardiometabolic specialist to provide counseling and support for lifestyle modification along with pharmacologic therapy as indicated to address the full range of any reproductive, endocrine, and cardiometabolic abnormalities.

Pharmacotherapy of Weight-loss and Obesity with a Focus on GLP 1-Receptor Agonists.

Obesity is a disease of epidemic proportions in the United States and contributes to morbidity and mortality for a large part of the population. In addition, the financial costs of this disease to society are high. Lifestyle modifications are key to prevention and treatment but adherence and long-term success have been challenging. Bariatric surgery has been available and pharmacologic approaches, first developed in the 1950s, continue to be an option; however, existing formulations have not provided optimal clinical efficacy and have had many concerning adverse effects. Over the last decade, glucagon-like peptide-1 (GLP-1) receptor agonists, a novel group of medications for the treatment of type 2 diabetes, were found to produce significant weight loss. Several formulations, at higher doses, received FDA approval for the treatment of obesity or those overweight with weight-related co-morbidities. More hormone-based therapies were and are being developed, some with dual or triple-receptor agonist activity. Their use, however, is not without questions and concerns as to long-term safety and efficacy, problems with cost and reimbursement, and how their use may intersect with public health efforts to manage the obesity epidemic. This review will focus on the GLP-1 receptor agonists currently used for weight loss and discuss their pharmacology, pertinent research findings establishing their benefits and risks, issues with prescribing these medications, and a perspective from a public health point of view.

Sodium-Glucose Cotransporter-2 Inhibitor Use is Associated with a Reduced Risk of Heart Failure Hospitalization in Patients with Heart Failure with Preserved Ejection Fraction and Type 2 Diabetes Mellitus: A Real-World Study on a Diverse Urban Population.

BACKGROUND: Limited evidence-based therapies exist for the management of heart failure with preserved ejection fraction (HFpEF). Sodium-glucose cotransporter-2 inhibitor (SGLT2i) use in patients with systolic heart failure (HFrEF) and type-2-diabetes mellitus (T2DM) is associated with improved cardiovascular (CV) and renal outcomes. OBJECTIVE: We sought to examine whether there is an association of SGLT2i use with improved CV outcomes in patients with HFpEF. PATIENTS AND METHODS: We conducted a single-center, retrospective review of patients with HFpEF and T2DM. The cohort was divided into two groups based on prescription of a SGLT2i or sitagliptin. The primary outcome was heart failure hospitalization (HFH); secondary outcomes were all-cause hospitalization and acute kidney injury (AKI). RESULTS: After propensity score matching, there were 250 patients (89 in the SGLT2i group, 161 in the sitagliptin group), with a mean follow-up of 295 days. Univariate Cox regression analysis showed that the SGLT2i group had a reduced risk of HFH versus the sitagliptin group (hazard ratio (HR) 0.13; 95% confidence interval (CI) (0.05-0.36); p < 0.001). The SGLT2i group had a decreased risk of all-cause hospitalization (HR 0.48; 95% CI (0.33-0.70); p < 0.001) and SGLT2i had a lower risk of AKI (HR 0.39; 95% CI (0.20-0.74); p = 0.004). CONCLUSIONS: The use of SGLT2is is associated with a reduced incidence of HFH and AKI in patients with HFpEF and T2DM.

Managing cardiometabolic risk factors across a woman's lifespan: A lipidologist's perspective.

A recent rise in atherosclerotic cardiovascular disease (ASCVD) mortality in women warrants a heightened focus on the cardiometabolic risk factors that are closely tied to increasing trends in obesity and suboptimal lifestyle. Polycystic ovarian syndrome (PCOS), adverse pregnancy outcomes (APOs) and nonalcoholic fatty liver disease (NAFLD) are often manifestations of cardiometabolic disease that convey cardiovascular risk requiring recognition foremost, as well as a targeted approach to treatment. Similarly, menopause is a time to reflect on a woman's cardiovascular risk as multiple cardiometabolic changes occur during this time. Contraceptives and menopausal replacement therapy (MRT) should be considered along with a woman's individual thrombotic and cardiovascular risk. Clinicians should be attuned to cardiometabolic risk factors throughout a woman's lifespan and familiar with strategies to reduce cardiovascular risk.

Prolonged QTc in HIV-Infected Patients: A Need for Routine ECG Screening.

BACKGROUND: With HIV-infected patients living longer, there is an increased burden of comorbidities related to aging, HIV itself, and polypharmacy. Cardiac morbidity is of particular importance. METHODS: This 2-group comparison study (156 HIV-positive and 105 HIV-negative patients) investigated the prevalence of abnormalities in and factors associated with an electrocardiogram (ECG) measure, corrected QT interval (QTc), where prolongation can lead to arrhythmia and sudden death. Medications prescribed (antiretroviral therapy, psychiatric medications, methadone, and antibiotics) at the time of ECG were noted. Patient characteristics, medications, QTc, and ECG characteristics were compared between the 2 groups. RESULTS: Prolongation (29% versus 19%) and extreme prolongation (6% versus 1%) in QTc were more frequent in those with HIV. Antiretroviral therapy was associated with lower odds of prolonged QTc (odds ratio [OR] = 0.35; P = .04), while methadone with higher odds (OR = 4.6; P = .01) in HIV-positive patients. With methadone and medication groups adjusted, HIV status was still associated with 17-millisecond longer QTc ( P = .04). CONCLUSION: This study provides evidence that patients with HIV may have clinically relevant longer QTc interval on ECG. Baseline and routine ECG monitoring may be warranted among patients living with HIV in clinical practice based on cumulative evidence.

JCL roundtable: Managing lipid disorders in patients with HIV.

The HIV-AIDS epidemic has provided one of the more challenging problems in treatment of infectious diseases. As antiretroviral drugs made a very marked improvement in controlling the immunodeficiency state and patients gained in their longevity, the concern with lipid abnormalities came to the fore. The initial drugs produced a form of metabolic syndrome accompanied by very elevated plasma triglyceride concentrations. Furthermore, the drugs used to control the virus were often metabolized in a manner that interfered with lipid lowering drug therapy. The antiviral agents have improved in many respects and the experience in managing the lipid disorders has added greatly to our ability to control these problems as well. This roundtable discussion has been conducted with 4 physicians who have been involved in management of large cohorts of patients with HIV infection and who have had a special interest in reduction of vascular disease risk.

Lipid Management in Human Immunodeficiency Virus.

The development and use of antiretroviral medications to treat patients infected with human immunodeficiency virus (HIV) has dramatically changed the course of this disease from one that was fatal to a chronic and more manageable condition. Recommendations and guidelines for the general population are presented in this review with suggestions as to how they may be applied to this patient population. Issues for which there is little or no information available are noted to highlight the many gaps in our knowledge regarding diagnosis and management of dyslipidemia for patients living with HIV.

Tricuspid Valve Replacement in an HIV-Infected Patient with Severe Tricuspid Regurgitation Secondary to Remote Endocarditis.

Surgical intervention for severe tricuspid regurgitation secondary to remote infective endocarditis has been infrequent, especially in patients also infected with the human immunodeficiency virus (HIV). We describe the case of a 62-year-old HIV-positive man, with a 24-year history of endocarditis caused by intravenous heroin use, who presented with severe tricuspid regurgitation. The patient was initially asymptomatic, was taking antiretroviral medications, and had a satisfactory CD4 count and an undetectable viral load, so we decided to manage the regurgitation conservatively. Two years later, he presented with biventricular heart failure and dyspnea. After surgical tricuspid valve replacement, his condition improved substantially. This case illustrates that HIV-infected patients with complex medical conditions can successfully undergo cardiac surgery.

Lipid management in human immunodeficiency virus.

The development and use of antiretroviral medications to treat patients infected with human immunodeficiency virus (HIV) has dramatically changed the course of this disease from one that was fatal to a chronic and more manageable condition. Recommendations and guidelines for the general population are presented in this review with suggestions as to how they may be applied to this patient population. Issues for which there is little or no information available are noted to highlight the many gaps in our knowledge regarding diagnosis and management of dyslipidemia for patients living with HIV.

Management of lipid disorders in patients living with HIV.

Since the discovery and development of antiretroviral therapy (ART), HIV has become a chronic disease with patients living longer lives and to ages where co-morbidities, such as cardiovascular disease (CVD) are prevalent. Diagnosis and management of risk factors for CVD, in particular dyslipidemia, have become an important part of the overall care for patients living with HIV infection. Existing guidelines and recommendations for the management of dyslipidemia for persons with HIV infection are largely based on guidelines for the general population. Clinical and epidemiologic research efforts are ongoing to provide information specific to patients living with HIV. This review offers a detailed guide for clinicians who manage dyslipidemia in patients infected with HIV. The first sections provide background information on dyslipidemia, risk stratification, and targets for lipid therapy. This is followed by a step-by-step approach for diagnosis and treatment with specific information on lipid drug use for patients with HIV. The recommendations presented here are based on existing guidelines for the general population, evidence from research in patients infected with HIV, and the clinical experience of the authors. Management issues for which little or no information is available specific to this patient population are noted and serve to highlight the many gaps in our knowledge that will need to be addressed.

Efficacy of Resistance Training as an Aid to Smoking Cessation: Rationale and Design of the Strength To Quit Study.

Despite recent declines in the rates of cigarette smoking, smoking remains prevalent among individuals with lower income, less education, and those with mental illness or HIV. Exercise is promoted as an aid to smoking cessation; however, the evidence for this recommendation is equivocal. To date, the majority of studies have only examined aerobic exercise; there is a poor understanding of the mechanisms of action; and there is an under-representation of male smokers. The goal of this trial is to produce new data that will help to address each of these gaps. A total of 206 male and female smokers will receive a brief smoking cessation education session prior to being randomized into a 12-week Resistance Training (RT) or Wellness Contact Control group. Both groups will have the option of using nicotine replacement therapy (NRT), and both will meet on-site twice per week during the 12-week program (24 total sessions). Follow-up assessments will occur at the end of the 12-weeks (3-month), and at a 6-month and 12-month (post-randomization) visit. Participants will not receive any additional smoking cessation treatment during follow-up; however, the RT group will receive a 9-month membership to a fitness center to encourage continued resistance training as a way to maintain cessation, and attendance will be tracked. The primary outcome is salivary-cotinine-verified 7-Day Point Prevalence Abstinence (PPA) at the 3-month assessment, and at the 6 and 12-month follow-ups. Secondary outcomes include effects of resistance training on nicotine withdrawal symptoms, indicators of mental health, and markers of disease risk.

Prevalence, treatment, and control of dyslipidemia and hypertension in 4278 HIV outpatients.

OBJECTIVE: Patients with HIV may have an increased risk of cardiovascular disease (CVD). The objective of this study was to determine the prevalence, treatment, and control of low-density lipoprotein cholesterol (LDL-C) dyslipidemia and hypertension in a population of HIV-infected patients at an HIV/AIDS clinic in New York City. METHODS: Review of electronic medical records of 4278 HIV-infected patients aged 20 years or older in a racially and ethnically diverse urban HIV/AIDS clinic based in a large tertiary hospital and designated New York State AIDS Center that provides comprehensive care. LDL-C dyslipidemia was defined according to the National Cholesterol Education Program Adult Treatment Panel III goals and hypertension according to Joint National Committee VII criteria. RESULTS: The prevalence of LDL-C dyslipidemia was 35%. Ninety percent of patients with LDL-C dyslipidemia were treated and 75% of those treated were at goal. Patients in high-risk groups (56%), including known coronary heart disease (57%) or coronary heart disease equivalents (62%), were less likely to be at LDL-C goal. The prevalence of hypertension was 43%. Seventy-five percent of patients with hypertension were treated but only 57% overall were at goal. CONCLUSIONS: Although most patients with HIV and LDL-C dyslipidemia or hypertension are treated, a significant percentage did not have adequate control of these risk factors. As patients with HIV are at higher risk for CVD and living to an age where CVD is more common, it will be important to identify ways to better manage and control CVD risk factors in this patient population. A comprehensive care model such as our setting may serve as an option.

No relation between coronary artery disease or electrocardiographic markers of disease in middle age and prenatal exposure to the Dutch famine of 1944-5.

OBJECTIVE AND SETTING: Associations between prenatal famine and coronary artery disease (CAD) have been examined before with inconsistent results. For further evaluation, we examined multiple cardiac risk markers in adult men and women with prenatal exposure to the Dutch famine of 1944-5. DESIGN: Birth cohort study of 407 men and women with prenatal famine exposure, 344 born before or after the famine as time controls, and 324 unexposed siblings as family controls. Study subjects underwent standardised interviews and clinical examinations at age approximately 58 years. OUTCOME MEASURES: CAD events from medical history and medical and electrocardiographic (ECG) markers of CAD risk, including 10-year (Framingham) estimates for myocardial infarction and coronary heart disease death, major and minor ECG abnormalities, ECG estimates of left ventricular hypertrophy and left ventricular mass, cardiac autonomic neuropathy measures including the QT index, resting heart rate, heart rate variability from subsequent N-N intervals, and ECG markers of minor T-wave abnormalities, changes in QRS/T frontal plane angle and ST-segment. RESULTS: No increase was seen in CAD risk (HR 1.17; 95% CI 0.73 to 1.88), Framingham risk (OR 1.14; 95% CI 0.90 to 1.44) or in ECG outcomes, adjusting for age and sex. Left ventricular mass estimated with body size was elevated by 3.78 g (95% CI 0.91 to 6.64) after prenatal famine, but showed a 0.65 g decrease (95% CI -2.63 to 1.34) when adjusted for body mass index. CONCLUSIONS: We see no relation between prenatal famine and adult CAD, Framingham risk, or any ECG predictors of increased cardiac disease risk.

Preparticipation athletic screening for genetic heart disease.

Sudden cardiac death (SCD) in young athletes is relatively uncommon but tragic when it occurs. Many of these deaths can be prevented by pre-exercise screening to identify cardiac abnormalities and those at high risk. Although recent research has provided much needed information on SCD in athletes, there remain significant gaps in the knowledge needed to determine an optimal screening protocol. This review examines the incidence and demographics of SCD in athletes and the difficulties in determining whether changes in an athlete's heart are due to training or represent a potentially malignant congenital abnormality. Current guidelines for screening and the intense debate over the use of the 12-lead electrocardiogram are discussed. Lastly, the importance of a response plan to an apparent SCD event that includes on-site/on-field automated external defibrillators will be discussed. A case study that illustrates the challenges in screening is presented.

Declining severity of myocardial infarction from 1987 to 2002: the Atherosclerosis Risk in Communities (ARIC) Study.

BACKGROUND: Death rates for coronary heart disease have been declining in the United States, but the reasons for this decline are not clear. One factor that could contribute to this decline is a reduction in the severity of acute myocardial infarction (MI). We hypothesized that for those patients hospitalized in the Atherosclerosis Risk in Communities (ARIC) Study with acute incident MI, there was a decline in MI severity from 1987 to 2002. METHODS AND RESULTS: The community surveillance component of the ARIC Study consisted of tracking residents 35 to 74 years of age with hospitalized MI or fatal coronary heart disease in 4 diverse communities. For incident, hospitalized MI, a probability sample of hospital discharges was validated and an MI classification was assigned according to an algorithm consisting of chest pain, ECG evidence, and cardiac biomarkers. Severity indicators were chosen from abstracted hospital charts validated as a definite or probable MI. With few exceptions, the MI severity indicators suggested a significant decline in the severity of MI during the period of 1987 to 2002. The percent of MI cases with major ECG abnormalities decreased as evidenced by a 1.9%/y (P=0.002) decline in the proportion of those with initial ST-segment elevation, a 3.9%/y (P<0.001) decline in those with subsequent Q-waves, and a 4.5%/y (P<0.001) decline in those with any major Q wave. Maximum creatine kinase and creatine kinase-MB values declined (5.2% and 7.6%; P<0.001, P<0.001 per year, respectively), although in the later years, maximum troponin I values remained stable (1.1%/y decline; P=0.66). The percent with shock declined (5.7%/y; P<0.001), although those with congestive heart failure remained stable. A combined severity score, the Predicting Risk of Death in Cardiac Disease Tool (PREDICT) score, also declined (0.2%/y; P<0.001). Results for blacks paralleled those of the entire group, as did results for women. CONCLUSIONS: Evidence from ARIC community surveillance suggests that the severity of acute MI has declined among community residents hospitalized for incident MI. This reduction in severity may have contributed, along with other factors, to the decline in death rates for coronary heart disease.

Sudden cardiac death in young competitive athletes due to genetic cardiac abnormalities.

Sudden cardiac death (SCD) in young athletes is generally caused by inherited cardiac disorders. While these events are relatively few compared to other cardiac deaths, they are tragic in that death occurs in a young, otherwise healthy person. The genetic abnormalities most associated with SCD are hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, long QT syndrome, Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia. As a result of growing awareness that these deaths can be prevented, guidelines have been issued in both Europe and the United States to help screen and determine qualification for young persons who want to participate in competitive athletics. There remains debate on the how extensive screening should be, in particular over the use of the 12-lead electrocardiogram (ECG), with European guidelines mandating ECG and United States guidelines not recommending routine use of the ECG.

Variation and temporal trends in the use of diagnostic testing during hospitalization for acute myocardial infarction by age, gender, race, and geography (the Atherosclerosis Risk In Communities Study).

The use of cardiovascular procedures has become routine in the management of acute myocardial infarction (MI). However, diagnostic testing beyond coronary revascularization procedures and use over time has not been well characterized. Records of 35- to 74-year-old adults hospitalized with MI in 4 US communities from 1987 to 2001 were abstracted using standardized data collection methods. Rates of procedure use and outcomes were compared by patient characteristics. Of 11,242 patients (mean age 61 years, 43% women, 22% black), angiography use increased substantially over time, echocardiography use increased more in women than men (interaction p<0.05), use of right-sided cardiac catheterization decreased, and use of nuclear scans and exercise tests remained constant. Men, whites, and locations with the highest angiography and right-sided cardiac catheterization use had lower noninvasive testing. In multivariate analysis, women had less angiograms and more echocardiograms obtained than men, but only in those with no previous MI before this hospitalization (both interaction p<0.05). Similarly, in those without previous MI, blacks were even less likely than whites to undergo angiography compared with those with a history of MI (interaction p=0.0001). Adjusted mortality rates were similar by gender, but mortality was higher in blacks than whites, a difference that decreased with adjustment for angiography use. In conclusion, in patients hospitalized with MI, use of many diagnostic cardiovascular procedures varied over time, with differences by gender, age, race, and geography that persisted over time unexplained by many measurable characteristics. There may also be continued perception of lower risk in women and blacks without a known diagnosis of MI.