Measuring lipoprotein(a) for cardiovascular disease prevention - in whom and when?

PURPOSE OF REVIEW: The aim of this study is to summarize major cardiovascular guideline recommendations on lipoprotein(a) and highlighting recent findings that emphasize how measuring lipoprotein(a) once in all adults is meaningful regardless of age, sex, comorbidities, or ethnicity. RECENT FINDINGS: Many international guidelines now recommend once in a lifetime measurement of lipoprotein(a) in all adult individuals to facilitate accurate risk prediction. Lipoprotein(a)-lowering therapy to reduce cardiovascular disease is on the horizon, with results from the first phase 3 trial expected in 2025. SUMMARY: Elevated lipoprotein(a) is an independent causal risk factor for atherosclerotic cardiovascular disease and aortic valve stenosis and measuring lipoprotein(a) once in all individuals regardless of age, sex, comorbidities, or ethnicity is meaningful to aid in risk stratification.

Lipoprotein(a) and Risks of Peripheral Artery Disease, Abdominal Aortic Aneurysm, and Major Adverse Limb Events.

BACKGROUND: Lp(a) (lipoprotein[a])-lowering therapy to reduce cardiovascular disease is under investigation in phase 3 clinical trials. High Lp(a) may be implicated in peripheral artery disease (PAD), abdominal aortic aneurysms (AAAs), and major adverse limb events (MALE). OBJECTIVES: The authors investigated the association of high Lp(a) levels and corresponding LPA genotypes with risk of PAD, AAA, and MALE. METHODS: The authors included 108,146 individuals from the Copenhagen General Population Study. During follow-up, 2,450 developed PAD, and 1,251 AAAs. Risk of MALE was assessed in individuals with PAD at baseline and replicated in the Copenhagen City Heart Study. RESULTS: Higher Lp(a) was associated with a stepwise increase in risk of PAD and AAA (P for trend <0.001). For individuals with Lp(a) levels ≥99th (≥143 mg/dL, ≥307 nmol/L) vs <50th percentile (≤9 mg/dL, ≤17 nmol/L), multivariable-adjusted HRs were 2.99 (95% CI: 2.09-4.30) for PAD and 2.22 (95% CI: 1.21-4.07) for AAA. For individuals with PAD, the corresponding incidence rate ratio for MALE was 3.04 (95% CI: 1.55-5.98). Per 50 mg/dL (105 nmol/L) genetically higher Lp(a) risk ratios were 1.39 (95% CI: 1.24-1.56) for PAD and 1.21 (95% CI: 1.01-1.44) for AAA, consistent with observational risk ratios of 1.33 (95% CI: 1.24-1.43) and 1.27 (95% CI: 1.15-1.41), respectively. In women smokers aged 70 to 79 years with Lp(a) <50th and ≥99th percentile, absolute 10-year risks of PAD were 8% and 21%, and equivalent risks in men 11% and 29%, respectively. For AAA, corresponding risks were 2% and 4% in women, and 5% and 12% in men. CONCLUSIONS: High Lp(a) levels increased risk of PAD, AAA, and MALE by 2- to 3-fold in the general population, opening opportunities for prevention given future Lp(a)-lowering therapies.

Lipoprotein(a) is linked to atherothrombosis and aortic valve stenosis independent of C-reactive protein.

AIMS: Recent evidence suggest that the lipoprotein(a)-associated risk of atherosclerotic cardiovascular disease (ASCVD) may be observed only in individuals with low-grade systemic inflammation. It was hypothesized that high lipoprotein(a) is a main driver for the risk of ASCVD, myocardial infarction, and aortic valve stenosis irrespective of C-reactive protein levels. METHODS AND RESULTS: A total of 68 090 individuals from the Copenhagen General Population Study, a prospective cohort study, were included. During a median follow-up of 8.1 years, 5104 individuals developed ASCVD, 2432 myocardial infarction, and 1220 aortic valve stenosis. The risk of ASCVD, myocardial infarction, and aortic valve stenosis increased with higher values of both lipoprotein(a) and C-reactive protein. For individuals with lipoprotein(a) in the 91st-100th percentiles (≥70 mg/dl, ≥147 nmol/l) vs. the 1st-33rd percentiles (≤6 mg/dl, ≤9 nmol/l), the multivariable-adjusted hazard ratio for ASCVD was 1.61 (95% confidence interval 1.43-1.81) for those with C-reactive protein <2 mg/l and 1.57 (1.36-1.82) for those with C-reactive protein ≥2 mg/l (P for interaction = 0.87). The corresponding values were 2.08 (1.76-2.45) and 1.65 (1.34-2.04) for myocardial infarction, and 2.01 (1.59-2.55) and 1.73 (1.31-2.27) for aortic valve stenosis, respectively (P for interaction = 0.15 and = 0.18). The highest absolute 10-year risks were found in men aged 70-79 years with lipoprotein(a) levels in the 91st-100th percentiles and C-reactive protein ≥2 mg/l, with 34% for ASCVD, 19% for myocardial infarction, and 13% for aortic valve stenosis. The corresponding values in women were 20%, 10%, and 8%, respectively. CONCLUSION: High lipoprotein(a) was a main driver for the risk of ASCVD, myocardial infarction, and aortic valve stenosis independent of C-reactive protein levels.

Birthweight, Childhood Body Mass Index, Height and Growth, and Risk of Polycystic Ovary Syndrome.

INTRODUCTION: Adult obesity is linked with polycystic ovary syndrome (PCOS), but the importance of body size at ages before PCOS is diagnosed is unknown. OBJECTIVE: To investigate associations between a woman's own birthweight, childhood body mass index (BMI), height and growth patterns in relation to her risk of PCOS. METHODS: We included 65,665 girls from the Copenhagen School Health Records Register, born in the period 1960-1996, with information on birthweight and measured weight and height at the ages of 7-13 years. Overweight was defined using International Obesity Task Force (IOTF) criteria. From the Danish National Patient Register, 606 women aged 15-50 years were identified. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by Cox regression analysis. RESULTS: Birthweight was not associated with PCOS. At the age of 7-13 years, girls with overweight had a higher risk of developing PCOS than girls without overweight; HR 2.83 (95% CI 2.34-3.42) at age 7 years and 2.99 (95% CI 2.38-3.76) at age 13 years. Furthermore, girls with overweight at both 7 and 13 years had a higher risk of developing PCOS than girls without overweight or overweight at only one age. Height was positively associated with PCOS risk at all ages. Girls who were persistently tall or changed from tall to average height had a higher risk of developing PCOS than girls with average height growth. CONCLUSION: Overweight and tall stature in childhood are positively associated with PCOS risk, but birthweight is not.

Early life body size and its associations with adult bladder cancer.

Background: Adult overweight is a potential bladder cancer (BC) risk factor, but little is known about size earlier in life.Aim: To investigate if birth weight, childhood body mass index (BMI), height and growth are associated with adult BC.Subjects and methods: Anthropometric information from birth and ages 7-13 on 315,763 individuals born 1930-1989 in the Copenhagen School Health Records Register was linked to national registers. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated by Cox regression.Results: 1145 individuals (839 men) were diagnosed with BC. Sex differences were not detected. Childhood BMI had positive associations and height had inverse associations with BC; at age 13, HR = 1.10 (95% CI: 1.02-1.18) per BMI z-score and HR = 0.94 (95% CI: 0.89-1.00) per height z-score. A pattern of above-average increases in BMI from 7 to 13 years had higher hazards of BC than average increases. Above-average growth in height was not significantly associated with BC. Compared with birth weights of 3.5 kg, low (2.5 kg) and high (4.5 kg) values were associated with increased hazards of BC; HR = 1.26 (95% CI: 1.01-1.58) and HR = 1.36 (95% CI: 1.09-1.70), respectively.Conclusions: A high BMI, a short height, excess BMI gain in childhood and low and high birth weights are associated with increased hazards of BC.

Early life body size, growth and risks of systemic lupus erythematosus - A large Danish observational cohort study.

OBJECTIVES: Adult obesity may increase the risks of systemic lupus erythematosus (SLE), and there are genetic links between adult height and SLE. Thus, it is plausible that size earlier in life may be important in the aetiology of SLE as well. We investigated whether birthweight, childhood body mass index (BMI; [kg/m2]), height and growth are associated with risks of adult SLE. METHODS: The study included 346,627 children from the Copenhagen School Health Records Register, born 1930-1996 with measured weights and heights from 7-13 years. Birthweight information was available from 1936. Linkages were made to the Danish National Patient Register for information on registrations of SLE. During follow-up, 435 individuals (366 women) were registered with SLE. Cox proportional hazards regressions were performed to estimate hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: No differences by sex were detected in any of the associations. Birthweight was not associated with SLE risks. Childhood BMI and height were positively and linearly associated with SLE risks. For BMI at age 7, the HR was 1.11 (95% CI: 1.01-1.23) per z-score. For height at age 7, the HR was 1.13 (95% CI: 1.02-1.24) per z-score. The estimates were similar in magnitude across all childhood ages for BMI and height. There were limited indications that change in BMI or growth in height during childhood influence the risks of SLE in adulthood. CONCLUSIONS: Childhood body size is associated with risks of adult SLE, which supports the hypothesis that early life factors are important in SLE aetiology.

Rapid HIV testing at gay pride events to reach previously untested MSM: U.S., 2009-2010.

We offered rapid HIV testing at social events frequented by young men who have sex with men (MSM), a group disproportionately affected by the HIV epidemic. We tested 1,312 MSM; of those MSM, 1,072 (81.7%) reported HIV testing history. Of those reporting HIV testing history, 550 (51.3%) were non-Hispanic black and 404 (37.7%) were aged <25 years. One hundred twenty-eight (11.9%) had never tested for HIV; 77 (7.2%) were preliminarily positive, with 15 (19.5%) being first-time testers. Factors associated with no previous HIV test included young age (13-24 years) (adjusted odds ratio [AOR] = 3.5, 95% confidence interval [CI] 1.9, 6.5) and non-Hispanic black (AOR=3.2, 95% CI 1.6, 6.4) or Hispanic (AOR=2.8, 95% CI 1.2, 6.3) race/ethnicity. HIV testing at Gay Pride events reaches young, previously untested MSM. This venue-based HIV testing approach at nonclinical sociocultural events is an additional strategy for HIV prevention goals to increase the number of people aware of their HIV infection with subsequent linkage to HIV care.

Reflections on the role of less-than-comprehensive (exclusionary) private health insurance hospital products in the Australian healthcare system.

The number of people in Australia that are currently covered by a hospital private health insurance product continues to rise every quarter. In September 2010, for the first time since the introduction of the public universal social insurance scheme, Medicare, more than 10million persons in Australia are covered by private health insurance. Although the number of persons covered by private health insurance continues to grow, the quality and level of cover that members are holding is changing significantly. In an effort to limit premium rises and to reduce the benefits paid for treatment, private health insurers have introduced, and moved a large number of existing members to, less-than-comprehensive private health insurance policies. These policies, known as 'exclusionary' policies, are changing the dynamics of private health insurance in Australia. After examining the emergence and prevalence of these products, this commentary gives three different examples to illustrate how such products are changing the nature of private health insurance in Australia and are now set to create a series of policy issues that will require future attention.

Missed opportunities for HIV testing in health care settings among young African American men who have sex with men: implications for the HIV epidemic.

Limited health care access and missed opportunities for HIV and other sexually transmitted infection (STI) education and testing in health care settings may contribute to risk of HIV infection. In 2008, we conducted a case-control study of African American men who have sex with men (MSM) in a southeastern city (Jackson, Mississippi) with an increase in numbers of newly reported HIV cases. Our aims were to evaluate associations between health care and HIV infection and to identify missed opportunities for HIV/STI testing. We queried 40 potential HIV-infected cases and 936 potential HIV-uninfected controls for participation in this study. Study enrollees included HIV-infected cases (n=30) and HIV-uninfected controls (n=95) who consented to participate and responded to a self-administered computerized survey about sexual risk behaviors and health care utilization. We used bivariate analysis and logistic regression to test for associations between potential risk factors and HIV infection. Cases were more likely than controls to lack health insurance (odds ratio [OR]=2.5; 95% confidence interval [CI]=1.1-5.7), lack a primary care provider (OR=6.3; CI=2.3-16.8), and to not have received advice about HIV or STI testing or prevention (OR=5.4; CI=1.3-21.5) or disclose their sexual identity (OR=7.0; CI=1.6-29.2) to a health care provider. In multivariate analysis, lacking a primary health care provider (adjusted odds ratio [AOR]=4.5; CI=1.4-14.7) and not disclosing sexual identity to a health care provider (AOR=8.6; CI=1.8-40.0) were independent risk factors for HIV infection among African American MSM. HIV prevention interventions for African American MSM should address access to primary health care providers for HIV/STI prevention and testing services and the need for increased discussions about sexual health, sexual identity, and sexual behaviors between providers and patients in an effort to reduce HIV incidence and HIV-related health disparities.

Demographic but not geographic insularity in HIV transmission among young black MSM.

OBJECTIVE: To understand patterns of HIV transmission among young black MSM and others in Mississippi. DESIGN: Phylogenetic analysis of HIV-1 polymerase (pol) sequences from 799 antiretroviral-naive persons newly diagnosed with HIV infection in Mississippi during 2005-2008, 130 (16%) of whom were black MSM aged 16-25 years. METHODS: We identified phylogenetic clusters and used surveillance data to evaluate demographic attributes and risk factors of all persons in clusters that included black MSM aged 16-25 years. RESULTS: We identified 82 phylogenetic clusters, 21 (26%) of which included HIV strains from at least one young black MSM. Of the 69 persons in these clusters, 59 were black MSM and seven were black men with unknown transmission category; the remaining three were MSM of white or Hispanic race/ethnicity. Of these 21 clusters, 10 included residents of one geographic region of Mississippi, whereas 11 included residents of multiple regions or outside of the state. CONCLUSION: Phylogenetic clusters involving HIV-infected young black MSM were homogeneous with respect to demographic and risk characteristics, suggesting insularity of this population with respect to HIV transmission, but were geographically heterogeneous. Reducing HIV transmission among young black MSM in Mississippi may require prevention strategies that are tailored to young black MSM and those in their sexual networks, and prevention interventions should be delivered in a manner to reach young black MSM throughout the state. Phylogenetic analysis can be a tool for local jurisdictions to understand the transmission dynamics in their areas.

Understanding disparities in HIV infection between black and white MSM in the United States.

OBJECTIVE: We evaluated several hypotheses for disparities in HIV infection between black and white MSM in the United States, including incarceration, partner HIV status, circumcision, sexual networks, and duration of infectiousness. DESIGN: The 2008 National HIV Behavioral Surveillance System (NHBS), a cross-sectional survey conducted in 21 US cities. METHODS: MSM were interviewed and tested for HIV infection. For MSM not previously diagnosed with HIV infection, we used logistic regression to test associations between newly diagnosed HIV infection and incarceration history, partner HIV status, circumcision status, and sexual networks (older partners, concurrency, and partner risk behaviors). For HIV-infected MSM, we assessed factors related to duration of infectiousness. RESULTS: Among 5183 MSM not previously diagnosed with HIV infection, incarceration history, circumcision status, and sexual networks were not independently associated with HIV infection. Having HIV-infected partners [adjusted odds ratio (AOR) = 1.9, 95% confidence interval (CI) = 1.2­3.0] or partners of unknown status (AOR = 1.4, CI = 1.1­1.7) were associated with HIV infection. Of these two factors, only one was more common among black MSM ­ having partners of unknown HIV status. Among previously diagnosed HIV-positive MSM, black MSM were less likely to be on antiretroviral therapy (ART). CONCLUSION: Less knowledge of partner HIV status and lower ART use among black MSM may partially explain differences in HIV infection between black and white MSM. Efforts to encourage discussions about HIV status between MSM and their partners and decrease barriers to ART provision among black MSM may decrease transmission.

HIV risk among young African American men who have sex with men: a case-control study in Mississippi.

OBJECTIVES: We conducted a case-control study in the Jackson, Mississippi, area to identify factors associated with HIV infection among young African American men who have sex with men (MSM). METHODS: During February to April 2008, we used surveillance records to identify young (16-25 years old) African American MSM diagnosed with HIV between 2006 and 2008 (case participants) and recruited young African American MSM who did not have HIV (controls). Logistic regression analysis was used to assess factors associated with HIV infection. RESULTS: In a multivariable analysis of 25 case participants and 85 controls, having older male partners (adjusted odds ratio [OR] = 5.5; 95% confidence interval [CI] = 1.8, 17.3), engaging in unprotected anal intercourse with casual male partners (adjusted OR = 6.3; 95% CI = 1.8, 22.3), and being likely to give in to a partner who wanted to have unprotected sex (adjusted OR = 5.0; 95% CI = 1.2, 20.6) were associated with HIV infection. CONCLUSIONS: Given the high prevalence of risk behaviors among the young African American MSM in our study, HIV prevention efforts must begin before or during early adolescence and need to focus on improving negotiation and communication regarding sex.

Sex with bisexual men among black female students at historically black colleges and universities.

BACKGROUND: Human immunodeficiency virus (HIV) disproportionately affects black women. Nearly two-thirds of all female HIV cases reported to the CDC are black, and HIV is the leading cause of death among black women aged 25 to 34 years. The greatest HIV transmission risk among black women is sexual intercourse with a man, although the role of bisexual men is not clear. METHODS: The CDC and collaborating partners conducted behavioral surveys at 7 historically black colleges and universities from January 2005 to April 2007. RESULTS: Of the 2705 black female students aged 18 to 29 years who were surveyed, 2040 (75%) reported being sexually active in the previous 12 months and, among sexually active women, 291 (14%) reported having sex with a bisexual man in the previous 12 months. Women who reported sex with a bisexual man were more likely than women who did not to report having at least 2 sex partners in the previous 12 months, having male and female sex partners, not using a condom at last intercourse, being in a committed relationship, never or infrequently attending church, and believing they were at increased risk for HIV infection. CONCLUSION: Heterosexually active black women who have engaged in sexual intercourse with bisexual men have a different HIV risk profile than other heterosexually active black women.

HIV risk behaviors and testing history in historically black college and university settings.

OBJECTIVES: From 2001 through 2005, African Americans accounted for the largest percentage of new cases of human immunodeficiency virus (HIV)/ acquired immunodeficiency syndrome (AIDS) in all age categories, especially among people aged 13 to 24 years. Although students attending historically black colleges and universities (HBCUs) report many of the behaviors that promote HIV transmission, their risk behaviors and HIV testing practices have not been well-characterized. We compared the demographic and behavioral characteristics of people who have been previously tested for HIV with those of people tested for the first time in this demonstration project to increase HIV testing at HBCUs. METHODS: The Centers for Disease Control and Prevention and collaborating partners conducted rapid HIV testing and behavioral surveys at HBCUs in Arkansas, Georgia, Mississippi, and Washington, D.C., from January 2005 to April 2007. We recruited a convenience sample of students and community members at different campus venues including student health centers, dormitories, and student activity centers. RESULTS: Our analysis included 5,291 people, 42% of whom reported they had never been tested for HIV. People who had been tested in the past were more likely to be older, believe they were at high risk for infection, have visited a health-care facility, and report behaviors that increased their risk of HIV infection. CONCLUSION: Respondents who believed they were at increased risk for HIV infection or reported behaviors that increased their risk for infection were more likely to have been tested for HIV. Future research should compare actual vs. perceived risk for HIV infection and contrast how each impacts HIV testing.

Role of Green Peach Aphid Flights in the Epidemiology of Potato Leaf Roll Disease in the Columbia Basin.

Three distinct and highly predictable green peach aphid (GPA) (Myzus persicae) flights that occur seasonally in the spring, summer, and fall were detected at a southern, central, and northern location in the Columbia Basin of the Northwestern United States. Intensity and timing of the flights was approximately the same at the three locations. Timing and number of alatae captured in the spring and summer flights was associated with heat unit accumulation. The spring flight, which originates on the overwintering peach tree host, colonized but did not introduce potato leafroll virus (PLRV) into virus-free potato plots. The summer flight, which originates from volunteer potatoes and spring herbs originally colonized by the spring flight, did introduce PLRV into virus-free potatoes. The fall flight was too late to affect potato production. When plots contained a point source of PLRV, the virus spread rapidly in a plant-to-plant mode to all plants in plots after aphids arrived in the spring. Rate of spread from point sources of infection was not affected by timing or intensity of the spring flight, but timing of virus spread in the plots depended on time of arrival of the aphids. Once PLRV was introduced to virus-free plots by the summer flight, virus spread to other plants within the plots. GPA overwintered on peach trees. Although GPA apterae and alatae were present on winter annual weed and crop hosts in the fall, none survived winters on these species. In addition to the GPA, one other vector of PLRV, Macrosiphum euphorbiae, was rarely collected in aphid traps. These results suggest that chemical control of aphids could be delayed until mid-July if PLRV-free potato seed were available.