Lipoprotein(a) and cardiovascular disease: prediction, attributable risk fraction and estimating benefits from novel interventions

Abstract Background Lipoprotein (a) (Lp(a)) measurement may help guide CVD risk prediction, is thought to be causal in several CVD outcomes, and phase 3 intervention trials of Lp(a) lowering agents are underway. We aimed to investigate the population attributable fraction due to elevated Lp(a) and its utility in CVD risk prediction. Methods In 413,724 participants from UK Biobank, associations of serum Lp(a) with composite fatal/nonfatal CVD (n=10,065 events), fatal CVD (n=3247), coronary heart disease (n=16,649), ischaemic stroke (n=3191), and peripheral vascular disease (n=2716) were compared using Cox models. Predictive utility was determined by C-index changes. The population attributable fraction was estimated. Results Median Lp(a) was 19.7nmol/L (interquartile interval 7.6–75.3nmol/L). 20.8% had Lp(a) values >100nmol/L; 9.2% had values >175nmol/L. After adjustment for classical risk factors, in participants with no baseline CVD and not taking a statin, 1 standard deviation increment in log Lp(a) was associated with a HR for fatal/nonfatal CVD of 1.09 (95% CI 1.07–1.11). Associations were similar for fatal CVD, coronary heart disease, and peripheral vascular disease. Adding Lp(a) to a prediction model containing traditional CVD risk factors improved the C-index by +0.0017 (95% CI 0.0009, 0.0026). We estimated that having Lp(a) values >100nmol/L accounts for 5.7% of CVD events in the whole cohort. We modelled that an ongoing trial to lower Lp(a) in patients with CVD and Lp(a) above ∼175nmol/L may be expected to reduce CVD risk by 20.3%, assuming causality, and an achieved Lp(a) reduction of 80%. Conclusions Population screening for elevated Lp(a) may help to predict CVD and target Lp(a) lowering drugs to those with markedly elevated levels, if such drugs prove efficacious. Population attributable fractions: Lp(a) Funding Acknowledgement Type of funding source: Other. Main funding source(s): Chest, Heart, and Stroke Association Scotland and British Heart Foundation

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Lipoprotein(a) and cardiovascular disease: prediction, attributable risk fraction and estimating benefits from novel interventions

10.1101/2020.03.30.20043554 ◽

2020 ◽

Author(s):

Paul Welsh ◽

Claire Welsh ◽

Carlos A Celis-Morales ◽

Rosemary Brown ◽

Lyn D Ferguson ◽

...

Keyword(s):

Risk Factors ◽

Coronary Heart Disease ◽

Heart Disease ◽

Vascular Disease ◽

Peripheral Vascular Disease ◽

Risk Prediction ◽

Population Attributable Fraction ◽

Attributable Fraction ◽

Peripheral Vascular ◽

Cvd Risk

AbstractBackgroundLipoprotein (a) (Lp(a)) is a CVD risk factor amenable to intervention and might help guide risk prediction.ObjectivesTo investigate the population attributable fraction due to elevated Lp(a) and its utility in risk prediction.MethodsUsing a prospective cohort study, 413,724 participants from UK Biobank, associations of serum Lp(a) with composite fatal/nonfatal CVD (n=10,065 events), fatal CVD (n=3247), coronary heart disease (n=16,649), ischaemic stroke (n=3191), and peripheral vascular disease (n=2716) were compared using Cox models. Predictive utility was determined by C-index changes. The population attributable fraction was estimated.ResultsMedian Lp(a) was 19.7nmol/L (interquartile interval 7.6-75.3nmol/L). 20.8% had Lp(a) values >100nmol/L; 9.2% had values >175nmol/L. After adjustment for classical risk factors, in participants with no baseline CVD and not taking a statin, 1 standard deviation increment in log Lp(a) was associated with a HR for fatal/nonfatal CVD of 1.09 (95%CI 1.07-1.11). Associations were similar for fatal CVD, coronary heart disease, and peripheral vascular disease. Adding Lp(a) to a prediction model containing traditional CVD risk factors improved the C-index by +0.0017 (95% CI 0.0009, 0.0026). We estimated that having Lp(a) values >100nmol/L accounts for 5.7% of CVD events in the whole cohort. We modelled that an ongoing trial to lower Lp(a) in patients with CVD and Lp(a) above ∼175nmol/L may reduce CVD risk by 20.3%, assuming causality, and an achieved Lp(a) reduction of 80%.ConclusionsPopulation screening for elevated Lp(a) may help to predict CVD and target Lp(a) lowering drugs, if such drugs prove efficacious, to those with markedly elevated levels.

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Peripheral vascular disease: consequence for survival and association with risk factors in the Speedwell prospective heart disease study.

Heart ◽

10.1136/hrt.72.2.128 ◽

1994 ◽

Vol 72 (2) ◽

pp. 128-132 ◽

Cited By ~ 88

Author(s):

D Bainton ◽

P Sweetnam ◽

I Baker ◽

P Elwood

Keyword(s):

Risk Factors ◽

Heart Disease ◽

Vascular Disease ◽

Peripheral Vascular Disease ◽

Peripheral Vascular ◽

Disease Study

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Macroangiopathy in type II diabetes

Acta Endocrinologica ◽

10.1530/acta.0.104s075 ◽

1983 ◽

Vol 104 (4_Suppl) ◽

pp. S75-S78

Author(s):

Antti Aro

Keyword(s):

Coronary Heart Disease ◽

Heart Disease ◽

Vascular Disease ◽

Peripheral Vascular Disease ◽

Type Ii Diabetes ◽

Clinical Manifestations ◽

Diabetic Patients ◽

Type Ii ◽

Peripheral Vascular ◽

Middle Aged

ABSTRACT. Macroangiopathy is the most important cause of mortality and morbidity in type II diabetes. The atherosclerotic process in diabetes is similar to that found in non-diabetic subjects, but the laesions are more extensive and the clinical manifestations are more common in diabetic subjects than in the non-diabetic population. In diabetic patients from different populations, the prevalence of macroangiopathy is variable, and the relative frequency follows the pattern found in the respective non-diabetic populations. The relative risk of large vessel disease is in most populations higher for female than for male diabetics. Coronary heart disease is the most important manifestation of macroangiopathy while cerebrovascular disease and peripheral vascular disease are less frequent, although all these manifestations occur at increased frequency among middle-aged diabetic subjects. The incidence of peripheral vascular disease seems to increase with increasing duration of diabetes in middle-aged subjects, whereas coronary heart disease is particularly frequent in type II diabetes already at the time of the diagnosis. Key words: atherosclerosis, complications, diabetes mellitus, macroangiopathy, mortality.

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