Diet and Lp(a): Does Dietary Change Modify Residual Cardiovascular Risk Conferred by Lp(a)?
Abstract
:1. Introduction
2. Lipoprotein(a) Structure and Unique Features
3. Lipoprotein(a) [Lp(a)] Is an Independent, Causal, Genetically Determined Cardiovascular Disease (CVD) Risk Factor
4. Public Health and Clinical Relevance of Lp(a) as a Contributor to Residual CVD Risk
5. Lp(a), Lipid-Lowering Therapeutics and Cardiovascular Benefit
6. The Effect of Dietary Intervention on Lp(a)
6.1. Saturated Fat Replacement
6.2. Diets with Different Macronutrient Compositions
7. Potential Mechanisms to Explain Pharmacological and Non-Pharmacological (e.g., Diet) Intervention-Induced Changes in Lp(a) Concentration
8. Measurement of Low-Density Lipoprotein Cholesterol (LDL-C) and Lp(a) Change
9. Future Direction
10. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Study | Design | Study Duration | Participants | N | Test Diets | Macronutrient Profiles of the Test Diets 1 | Lp(a) mg/dL (Mean ± SEM) | LDL-C (Measured) mg/Dl (Mean ± SEM) | SFA Replacement Effect Summary | |||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
CHO | PRO | Total Fat | SFA | MUFA | PUFA | |||||||||
Ginsberg et al. 1998 (USA) DELTA 1 [80] | 4-site multicenter, randomized, 3 period crossover, controlled feeding trial | 8-week diet periods (4–6 washout) | Normolipidemic, aged 22–65 years; 55% women (30% black; 32% postmenopausal) and 45% men (20% black) | 103 | AAD | 48 | 15 | 34.3 | 15.0 | 12.8 | 6.5 | 15.5 ± 1.8 a | 131.4 ± 2.7 2,a | SFA→CHO: ↑ Lp(a) ↓LDL-C |
Step 1 | 55 | 15 | 28.6 | 9 | 12.9 | 6.7 | 17.0 ± 1.8 b | 122.2 ± 2.6 2,b | ||||||
Low-SFA | 59 | 15 | 25.3 | 6.1 | 12.4 | 6.7 | 18.2 ± 1.9 c | 116.9 ± 2.6 2,c | ||||||
Berglund et al. 2007 (USA) DELTA 2 [81] | 4-site multicenter, randomized, 3 period crossover, controlled feeding trial | 7-week diet periods (4–6 washout) | Low HDL-C, moderately elevated triglycerides and insulin;aged 21–65 years; 39% women (18% black) and 61% men (8% black) | 85 | AAD | 49 | 15.3 | 35.8 | 15.6 | 14.4 | 5.8 | 9.9 ± 1.4 a | 128 ± 3.1 a | SFA→CHO: ↑ Lp(a) ↓LDL-C SFA→MUFA: ↑ Lp(a) ↓LDL-C |
MUFA | 48.8 | 15.5 | 35.7 | 8.7 | 20.8 | 6.2 | 11.0 ± 1.5 b | 120 ± 3.1 b | ||||||
Step 1 | 54.9 | 16.1 | 29 | 8 | 15.5 | 5.5 | 11.9 ± 1.6 b | 119 ± 3.1 b | ||||||
Clevidence et al. 1997 (USA) [82] | Randomized, 4 period, crossover, controlled feeding trial | 6-week diet periods (no washout) | 80–120% of desirable BMI; aged 25–65 years; total cholesterol 50th–75th percentile; HDL-C > 35 mg/dl (men) or >40 mg/dL (women) | 58 | SFA | 45 | 15 | 40 | 19.3 4 | 10.9 5 | 6.1 6 | 21.9 ± 0.4 a | 141 ± 9.3 2,a | SFA→MUFA: ↑ Lp(a) ↓LDL-C |
Oleic | 46 | 15 | 39 | 13.4 4 | 16.7 5 | 6.1 6 | 23.8 ± 0.4 b | 129 ± 9.3 2,b | ||||||
Moderate trans fat 7 | 46 | 15 | 39 | 13.0 4 | 14.1 5 | 6.0 6 | 23.8 ± 0.4 b | 137 ± 9.3 2,c | ||||||
High trans fat 8 | 46 | 15 | 39 | 12.7 4 | 11.4 5 | 6.2 6 | 24.7 ± 0.4 b | 139 ± 9.3 2,a,c | ||||||
Mensink et al. 1992 (The Netherlands) Experiment 1 [85] | 2 group parallel, controlled feeding trial | 17 days–control run-in diet 36 days–MUFA or PUFA | Young, normolipidemic (mean total cholesterol 193 ± 31 mg/dL), non-obese (mean BMI 21.6 ± 2.0 kg/m2) students | 58 | High SFA (control) | 48–49 | 13 | 36.7 | 19.3 | 11.5 | 4.6 | Pre MUFA: 8.4 (0–34.0) 9 Pre PUFA: 3.7 (0–23.5) 9 | Pre MUFA: 128 ± 29 2,3 Pre PUFA: 129 ± 26 2,3 | SFA→MUFA: ←→ Lp(a) ↓LDL-C SFA→PUFA: ←→ Lp(a) ↓LDL-C |
29 | MUFA | 48–49 | 13 | 37.4 | 12.9 | 15.1 | 7.9 | 9.1 (0–33.6) 9 | 104 ± 26 2,3,a | |||||
29 | PUFA | 48–49 | 13 | 37.6 | 12.6 | 10.8 | 12.7 | 4.0 (0–24.0) 9 | 111 ± 23 2,3,b | |||||
Mensink et al. 1992 (The Netherlands) Experiment 2 [85] | Randomized, 3 period, crossover, controlled feeding trial | 3-week diet periods (washout not reported) | Mean total cholesterol 184 ± 31 mg/dL; Mean BMI 21.5 ± 2.1 kg/m2 | 59 | SFA | 46 | 13–14 | 38.8 | 19.4 | 14.7 | 3.4 | 2.6 (0–44.7) 9,a | 121 ± 22 2,3,a | SFA→MUFA: ↑ Lp(a) ↓LDL-C |
Oleic acid 10 | 46 | 13–14 | 39.6 | 9.5 | 24.1 | 4.6 | 3.2 (0–48.4) 9,b | 103 ± 21 2,3,b | ||||||
Trans fat | 46 | 13–14 | 40.2 | 10.0 | 13.3 | 4.6 | 4.5 (0–51.0) 9,c | 118 ± 24 2,3c | ||||||
Mensink et al. 1992 (The Netherlands) Experiment 3 [85] | Randomized, 3 period, crossover, controlled feeding trial | 3-week diet periods (washout not reported) | Mean total cholesterol 195 ± 25 mg/dL; Mean BMI 22.0 ± 2.3 kg/m2 | 56 | Stearate | 44–47 | 12–13 | 43.5 | 20.1 (11.8 stearic acid) | 16.3 | 4.3 | 6.9 (0–74.9) 9,a | 116 ± 27 2,3,a | SFA→PUFA: ←→ Lp(a) ↓LDL-C |
Linoleate | 44–47 | 12–13 | 41.1 | 11.0 (2.8 stearic acid) | 15.7 | 12.5 | 6.9 (0–78.2) 9,a | 109 ± 24 2,3,b | ||||||
Trans fat 11 | 44–47 | 12–13 | 39.7 | 10.3 (3.0 stearic acid) | 15.6 | 3.8 | 8.5 (0–89.1) 9,b | 119 ± 25 2,3,a | ||||||
Muller et al. 2003 (Norway) [83,84] | Randomized, 3 period, crossover, controlled feeding trial | 3-week diet periods (1-week washout) | Female students, aged 31 ± 10, BMI 24.5 ± 3.2 kg/m2 | 25 | High saturated fat | 46.7 | 14.9 | 38.4 | 22.7 12 | 5.5 | 3.9 | 31.6 ± 48.7 3,a | 124 ± 30 2,3,a | SFA 12→MUFA/PUFA: ↑ Lp(a) ↓LDL-C SFA 12→CHO: ←→ Lp(a) ←→ LDL-C |
Low saturated fat | 63.8 | 16.5 | 19.7 | 10.5 12 | 3.5 | 2.3 | 34.0 ± 49.3 3,a,b | 121 ± 26 2,3,a | ||||||
High MUFA/PUFA | 46.8 | 15 | 38.2 | 2.4 12 | 14.1 | 15.6 | 35.8 ± 51.5 3,b | 97 ± 25 2,3,b |
Study | Design | Study Duration | Participants | N | Test diets | Macronutrient Profiles of the Test Diets 1 | Lp(a) mg/dL (Mean ± SEM) | LDL-C (Measured) mg/dL (Mean ± SEM) | Effect Summary | |||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
CHO | PRO | Total Fat | SFA | MUFA | PUFA | |||||||||
Omni Heart (USA) [90,91] | Randomized, 3 period, crossover, controlled feeding trial | 6-week diet periods (2–4 week washout) | Systolic blood pressure 120–159 mmHg or diastolic blood pressure 80–99 mmHg, aged > 30 years; 46% women (70% black) and 54% men (44% black) | 155 | CHO | 58 | 15 | 27 | 6 | 13 | 8 | 3.2 (2.2, 4.2) 2,*,a | -11.6 (-14.6, -8.6) 2,3,*,a | CHO→PRO ↑ Lp(a) ↓LDL-C CHO→MUFA/PUFA ↑ Lp(a) ↓LDL-C MUFA/PUFA→PRO ↑ Lp(a) ↓LDL-C |
Protein | 48 | 25 | 27 | 6 | 13 | 8 | 4.7 (3.7, 5.7) 2, *,b | -14.2 (-17.5 -10.9) 2,3,*,b | ||||||
Unsaturated fat | 48 | 15 | 37 | 6 | 21 | 10 | 2.1 (1.1, 3.1) 2,*,c | -13.1 (-16.4, -9.8) 2,3,*,a,b | ||||||
Faghihnia et al. 2010 (USA) [92] | Randomized, 2 period, crossover, trial | 4-week diet periods (no washout) | Body weight <130% of ideal; aged >20 years; 97% men | 63 | High-fat, low-CHO | 45 | 15 | 40 | 13 | 11 | 14 | 17.8 ± 12.8 4,a | 124.0 ± 31.5 3,4,a | High-fat, low-CHO → Low-fat, high-CHO ↑ Lp(a) ↓LDL-C |
Low-fat, high-CHO | 65 | 15 | 20 | 5 | 10 | 5 | 19.9 ± 13.7 4,b | 117.3 ± 30.7 3,4,b | ||||||
Berryman et al. 2015 (USA)) [93] | Randomized, 2 period crossover, controlled feeding trial | 6-week diet periods (2-week washout) | LDL-C 121–190 mg/dL women or 128–194 mg/dL men; aged 30–65 years; BMI 20–35 kg/m2; 54% women | 48 | Almond | 51.3 | 16.4 | 32.3 | 7.7 | 13.9 | 8.4 | 7.7 ± 0.8 a | 129 ± 3 a | Lower fat, higher CHO → Higher fat, lower CHO diet with almonds ↑ Lp(a) ↓LDL-C |
Control | 58.4 | 15.2 | 26.4 | 7.8 | 10.4 | 6.2 | 6.7 ± 0.8 b | 135 ± 3 b | ||||||
Jenkins et al. 2002 (Canada) [94] | Randomized, 3 period crossover, trial | 4-week diet periods (>2-week washout) | Hyperlipidemic (LDL-C >159 mg/dL); aged 48–86 years; BMI 20.5–31.5 kg/m2; 56% men and 44% postmenopausal women | 27 | Full-dose almond | 44.8 | 17.4 | 36.0 | 7.2 | 18.9 | 8.2 | 14.2 ± 2.9 a | 155 ± 4.6 3,a | Lower fat, higher CHO → Higher fat, lower CHO diet with almonds ↓ Lp(a) ↓LDL-C |
Half-dose almond | 48.4 | 17.6 | 32.1 | 7.5 | 14.5 | 8.0 | 15.4 ± 3.2 | 159 ± 4.6 3,a | ||||||
Control | 54.5 | 17.5 | 26.3 | 7.0 | 9.0 | 8.0 | 15.5 ± 3.2 b | 163 ± 5.0 3,b | ||||||
Lee et al. 2017 (USA) [97] | Randomized, 4 period crossover, controlled feeding trial | 4-week diet periods (2-week washout) | Overweight or obese; aged 30–70 years; LDL-C 25th–95th percentile | 31 | AAD | 49 | 17 | 34 | 13 | 13 | 7 | 4.9 (4.1, 5.8) 5 | 135.6 ± 2.8 a | Average American diet → Higher fat, lower saturated fat diet with almonds or almonds + chocolate ←→ Lp(a) ↓LDL-C Average American diet → higher carbohydrate diet with chocolate ←→ Lp(a) ←→LDL-C |
Almond | 48 | 16 | 36 | 8 | 16 | 9 | 5.3 (4.5, 6.3) 5 | 126.4 ± 2.8 b | ||||||
CHOC | 51 | 16 | 33 | 12 | 12 | 6 | 4.6 (3.9, 5.5) 5 | 136.1 ± 2.8 a | ||||||
Almond+ CHOC | 49 | 16 | 35 | 9 | 9 | 8 | 5.1 (4.3, 6.1) 5 | 128.9 ± 2.8 b | ||||||
Rajaram et al. 2001 (USA) [95] | Randomized, 2 period crossover, controlled feeding trial | 4-week diet periods (no washout) | Healthy; total cholesterol 15th–80th percentile | 23 | Step 1 | 56.8 | 14.5 | 28.3 | 8.2 | 11.0 | 6.3 | 25 ± 22 4,a | 117.9 ± 21.7 4,6,a | Pecan-enriched higher fat, lower carbohydrate diet → lower fat, higher carbohydrate diet ↓ Lp(a) ↓LDL-C |
Pecan-enriched | 47.2 | 13.1 | 39.6 | 8.1 | 18.9 | 10.7 | 21 ± 18 4,b | 105.6 ± 19.7 4,6,b | ||||||
Zambon et al. (Spain) [96] | Randomized, 2 period crossover, controlled feeding trial | 4-week diet periods (no washout) | Polygenic hypercholesterolemia | 49 | Control (Mediterranean) | 49.8 | 19.0 | 31.2 | 6.9 | 17.5 | 4.8 | 34 ± 24 4,a | 185 ± 25 4,a | Mediterranean diet → Mediterranean diet with walnuts (35% of total fat; 41–56 g/day) ↓ Lp(a) ↓LDL-C |
Walnut (Mediterranean) | 48 | 17.9 | 33.2 | 6.0 | 13.5 | 11.7 | 32 ± 22 4,b | 174 ± 30 4,b |
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Enkhmaa, B.; Petersen, K.S.; Kris-Etherton, P.M.; Berglund, L. Diet and Lp(a): Does Dietary Change Modify Residual Cardiovascular Risk Conferred by Lp(a)? Nutrients 2020, 12, 2024. https://doi.org/10.3390/nu12072024
Enkhmaa B, Petersen KS, Kris-Etherton PM, Berglund L. Diet and Lp(a): Does Dietary Change Modify Residual Cardiovascular Risk Conferred by Lp(a)? Nutrients. 2020; 12(7):2024. https://doi.org/10.3390/nu12072024
Chicago/Turabian StyleEnkhmaa, Byambaa, Kristina S. Petersen, Penny M. Kris-Etherton, and Lars Berglund. 2020. "Diet and Lp(a): Does Dietary Change Modify Residual Cardiovascular Risk Conferred by Lp(a)?" Nutrients 12, no. 7: 2024. https://doi.org/10.3390/nu12072024
APA StyleEnkhmaa, B., Petersen, K. S., Kris-Etherton, P. M., & Berglund, L. (2020). Diet and Lp(a): Does Dietary Change Modify Residual Cardiovascular Risk Conferred by Lp(a)? Nutrients, 12(7), 2024. https://doi.org/10.3390/nu12072024