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Associations between cardiovascular disease, cancer, and very low high-density lipoprotein cholesterol in the REasons for Geographical and Racial Differences in Stroke (REGARDS) study.

ABSTRACT: Aims:Relatively little is known about the health outcomes associated with very low plasma concentrations of high-density lipoprotein cholesterol (HDL-C) mainly because of the small numbers of individuals with such extreme values included in clinical trials. We, therefore, investigated the association between low and very low HDL-C concentration at baseline and incident all-cause-mortality, death from malignant disease (i.e. cancer), and with fatal or non-fatal incident coronary heart disease (CHD) in individuals from the Reasons for Geographical And Racial Differences in Stroke (REGARDS) study. Methods and results:Analysis was based on 21 751 participants from the REGARDS study who were free of CHD, other cardiovascular disease, and cancer at baseline and were categorized by baseline HDL-C into <30?mg/dL (very low), 30-<40?mg/dL (low), and ?40?mg/dL (reference). A series of incremental Cox proportional hazards models were employed to assess the association between the HDL-C categories and outcomes. Statistical analysis was performed using both complete case methods and multiple imputations with chained equations. After adjustment for age, race, and sex, the hazard ratios (HRs) comparing the lowest and highest HDL-C categories were 1.48 [95% confidence interval (CI) 1.28-1.73] for all-cause mortality, 1.35 (95% CI 1.03-1.77) for cancer-specific mortality and 1.39 (95% CI 0.99-1.96) for incident CHD. These associations became non-significant in models adjusting for demographics, cardiovascular risk factors, and treatment for dyslipidaemia. We found evidence for an HDL paradox, whereby low HDL (30-<40?mg/dL) was associated with reduced risk of incident CHD in black participants in a fully adjusted complete case model (HR 0.63; 95% CI 0.46-0.88) and after multiple imputation analyses (HR 0.76; 95% CI 0.58-0.98). HDL-C (<30?mg/dL) was significantly associated with poorer outcomes in women for all outcomes, especially with respect to cancer mortality (HR 2.31; 95% CI 1.28-4.16) in a fully adjusted complete case model, replicated using multiple imputation (HR 1.81; 95% CI 1.03-3.20). Conclusion:Low HDL-C was associated with reduced risk of incident CHD in black participants suggesting a potential HDL paradox for incident CHD. Very low HDL-C in women was significantly associated with cancer mortality in a fully adjusted complete case model.

SUBMITTER: Penson P

PROVIDER: S-EPMC6302258 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Associations between cardiovascular disease, cancer, and very low high-density lipoprotein cholesterol in the REasons for Geographical and Racial Differences in Stroke (REGARDS) study.

Penson Peter P Long D Leann DL Howard George G Howard Virginia J VJ Jones Steven R SR Martin Seth S SS Mikhailidis Dimitri P DP Muntner Paul P Rizzo Manfredi M Rader Daniel J DJ Safford Monika M MM Sahebkar Amirhossein A Toth Peter P PP Banach Maciej M

Cardiovascular research 20190101 1

<h4>Aims</h4>Relatively little is known about the health outcomes associated with very low plasma concentrations of high-density lipoprotein cholesterol (HDL-C) mainly because of the small numbers of individuals with such extreme values included in clinical trials. We, therefore, investigated the association between low and very low HDL-C concentration at baseline and incident all-cause-mortality, death from malignant disease (i.e. cancer), and with fatal or non-fatal incident coronary heart dis ...[more]

PMID: 30576432

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Project description:AimsRecent findings have demonstrated the important contribution of inflammation to the risk of cardiovascular disease (CVD) in individuals with optimally managed low density lipoprotein cholesterol (LDL-C). We explored relationships between LDL-C, high sensitivity C-reactive protein (hs-CRP), and clinical outcomes in a free-living US population.Methods and resultsWe used data from the REasons for Geographical And Racial Differences in Stroke (REGARDS), and selected individuals at 'high risk' for coronary events with a Framingham Coronary Risk Score of ≥10% or atherosclerotic cardiovascular disease (ASCVD) risk ≥7.5% in order to explore relationships between low LDL-C [<70 mg/dL (1.8 mmol/L) in comparison to ≥70 mg/dL (1.8 mmol/L)]; hs-CRP <2 compared with ≥2 mg/L and clinical outcomes [all-cause mortality, incident coronary heart disease (CHD), and incident stroke]. To assess the association between the LDL-C and hs-CRP categories and each outcome, a series of incremental Cox proportional hazards models were employed on complete cases. To account for missing observations, the most adjusted model was used to interrogate the data using multiple imputation with chained equations (MICE). In this analysis, 6136 REGARDS high-risk participants were included. In the MICE analysis, participants with high LDL-C (≥70 mg/dL) and low hs-CRP (<2 mg/L) had a lower risk of incident stroke [hazard ratio (HR) 0.69, 0.47-0.997], incident CHD (HR 0.71, 0.53-0.95), and CHD death (HR 0.70, 0.50-0.99) than those in the same LDL-C category high hs-CRP (≥2 mg/L). In participants with high hs-CRP (≥2 mg/dL), low LDL-C [<70 mg/dL (1.8 mmol/L)] was not associated with additional risk reduction of any investigated outcome, but with the significant increase of all-cause mortality (HR 1.37, 1.07-1.74).ConclusionsIn this high-risk population, we found that low hs-CRP (<2 mg/L) appeared to be associated with reduced risk of incident stroke, incident CHD, and CHD death, whereas low LDL-C (<70 mg/dL) was not associated with protective effects. Thus, our results support other data with respect to the importance of inflammatory processes in the pathogenesis of CVD.

Project description:BACKGROUND:Despite concerns about adverse neurocognitive events raised by prior trials, pharmacological PCSK9 (proprotein convertase subtilisin/kexin type-9) inhibition was not associated with neurocognitive effects in a recent phase 3 randomized trial. PCSK9 loss-of-function (LOF) variants that result in lifelong exposure to lower levels of low-density lipoprotein cholesterol can provide information on the potential long-term effects of lower low-density lipoprotein cholesterol on neurocognitive impairment and decline. METHODS:We investigated the association between PCSK9 LOF variants and neurocognitive impairment and decline among black REGARDS study (Reasons for Geographic and Racial Differences in Stroke) participants with (n=241) and without (n=10?454) C697X or Y142X LOF variants. Neurocognitive tests included the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) battery (Word List Learning, World List Delayed Recall, Semantic Animal Fluency) and Six-Item Screener (SIS) assessments, administered longitudinally during follow-up. Neurocognitive impairment was defined as a score ?1.5 SD below age, sex, and education-based stratum-specific means on 2 or 3 CERAD assessments or, separately, a score <5 on any SIS assessment at baseline or during follow-up. Neurocognitive decline was assessed using standardized continuous scores on individual neurocognitive tests. RESULTS:The mean sample age was 64 years (SD, 9), 62% were women, and the prevalence of neurocognitive impairment at any assessment was 6.3% by CERAD and 15.4% by SIS definitions. Adjusted odds ratios for neurocognitive impairment for participants with versus without PCSK9 LOF variants were 1.11 (95% confidence interval [CI], 0.58-2.13) using the CERAD battery and 0.89 (95% CI, 0.61-1.30) using the SIS assessment. Standardized average differences in individual neurocognitive assessment scores over the 5.6-year (range, 0.1-9.1) study period ranged between 0.07 (95% CI, -0.06 to 0.20) and -0.07 (95% CI, -0.18 to 0.05) among participants with versus without PCSK9 LOF variants. Patterns of neurocognitive decline were similar between participants with and without PCSK9 LOF variants (all P>0.10). Odds ratios for neurocognitive impairment per 20 mg/dL low-density lipoprotein cholesterol decrements were 1.02 (95% CI, 0.96-1.08) and 0.99 (95% CI, 0.95-1.02) for the CERAD and SIS definitions of impairment, respectively. CONCLUSIONS:These results suggest that lifelong exposure to low PCSK9 levels and cumulative exposure to lower levels of low-density lipoprotein cholesterol are not associated with neurocognitive effects in blacks.

Project description:Albuminuria is an important risk factor for progressive chronic kidney disease (CKD) and is more prevalent in black than white adults. We sought to determine the association between low income and albuminuria and whether this association differs for blacks and whites.Cross-sectional study.9,144 black and 13,684 white US adults 45 years and older in the population-based Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study.Self-reported annual household income category (?$75,000, $35,000-$74,999, $20,000-$34,999, and <$20,000); black and white race.Albuminuria defined as high (30-300 mg/g) or very high (>300 mg/g) urinary albumin-creatinine ratio (ACR). Multinomial logistic regression used to examine the race-stratified association between categories of income and albuminuria (normal, high, or very high ACR).Overall, geometric mean ACR was 10.2 mg/g and was higher for blacks (11.8 mg/g) than whites (9.3 mg/g), P<0.001. Lower income was associated with a higher prevalence of albuminuria for both whites and blacks in unadjusted analyses. After adjustment for demographics, lifestyle factors, comorbid illnesses, and estimated glomerular filtration rate, there was a trend toward a stronger association between lower income levels and high ACR in blacks (ORs of 1.38 [95% CI, 1.07-1.77], 1.36 [95% CI, 1.05-1.75], and 1.58 [95% CI, 1.21-2.05] for income levels of $35,000-$74,999, $20,000-$34,999, and <$20,000, respectively; reference group is those with income?$75,000) compared with whites (ORs of 0.95 [95% CI, 0.81-1.12], 0.95 [95% CI, 0.79-1.14], and 1.26 [95% CI, 1.02-1.55], respectively); P interaction=0.08 between race and income. Results were similar for very high ACR and subgroups of participants with diabetes or hypertension.Cross-sectional design; not all REGARDS participants provided their annual income.Lower income may be associated more strongly with albuminuria in blacks than whites and may be a determinant of racial disparities in albuminuria.

Dataset Information

Associations between cardiovascular disease, cancer, and very low high-density lipoprotein cholesterol in the REasons for Geographical and Racial Differences in Stroke (REGARDS) study.

Publications

Associations between cardiovascular disease, cancer, and very low high-density lipoprotein cholesterol in the REasons for Geographical and Racial Differences in Stroke (REGARDS) study.

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